For Medical Professionals
- Earn 19.5 CME Credits
- $375, reserve your spot before registration closes!
- $99, reserve your spot before registration before Feb 9th!
- Get access to a special conference March 5th - "Translating the Scince into the Practical" as a follow-up to this event!
*Conference will be conducted in EST*
*If you cannot attend live, you can still register and the recording will be made available to you for 3 months after the conference - including for CMEs*
Join us virtually February 9-11, 2022, for a landmark leadership conference sponsored by Georgetown University and The Foundation for Total Recovery.
Guest speakers from around the world will include distinguished specialists from Oxford, Columbia, Duke, and even the leading medical center in the Middle East—Sheba Medical Center in Israel. Plan to join us, as we have an exciting three days scheduled.
This conference is a critical and long overdue rethink of how we approach ME/CFS, neuropsychiatric disorders, PANS/PANDAS, chronic Lyme, fibromyalgia, and even long-haul COVID-19.
We believe the treatment of these diseases needs to be viewed through a different lens—that of immune dysregulation resulting in neuroinflammation. We have to give up our belief that these are standalone diseases—especially if we want the best outcomes for patients.
This is a radical paradigm shift, but we need it badly. We hope as practitioners, patients and caregivers you will join us for this discussion as we discuss the future of diagnostic, treatment and recovery for these patients.
The goals of this conference are three-fold:
- First, we will explore the role of genetic and epigenetic factors that predispose an individual for immune dysregulation.
- Secondly, we will analyze the current evidence for infection-mediated immune dysregulation as it relates to Fibromyalgia, ME/CFS, neuropsychiatric illnesses, Post-Lyme syndrome, PANS/PANDAS and the post COVID-19 long haul syndrome.
- Thirdly, we will examine current and new diagnostic testing procedures and treatment options for these conditions.
If you have any problems registering please email info@brainonfire.org
Morning Sessions:
Dr. Gary Kaplan & Organizing Committee
Opening Notes
Feb 09, 2022 – 8:00 am – 8:15 am
Dr. Gary Kaplan
Epidemiology: How Big is the Problem? Immune Dysregulation Secondary to Infections as a Cause of Chronic Disease. From Symptoms to a New Pathophysiologic Understanding of Chronic Illness
Feb 09, 2022 – 8:15 am – 9:00 am
There are approximately 20 million people in the United Stated and millions more worldwide suffering with a wide range of conditions for which the pathophysiology is at best poorly understood. These conditions include ME/CFS, Fibromyalgia, Chronic Lyme, post covid syndrome and a number of neuropsychiatric diseases. In addition, there are millions of children struggling with PANDAS and PANS. Common to all of these conditions is significant overlapping presentations. Pathophysiological common to all of these conditions is evidence of neuroinflammation and at least in a subset of all of these conditions there is evidence for an infectious etiology and immune dysregulation. This lecture will discuss the diagnostic criteria, demographics and overlapping presentations of these conditions. The economic costs and person burden of these conditions will also be discussed. The lecture will also briefly discuss a proposed definition of autoimmune encephalopathy as distinct from encephalitis.
Learning objectives
1) Know the diagnostic criteria for ME/CFS, Fibromyalgia, PANS/PANDAS,
2) Know the demographics of each of these conditions
3) Understand the economic and personal burden of these conditions
Bio:
Gary Kaplan, DO, is the founder and medical director of the Kaplan Center for Integrative Medicine, and author of Total Recovery: A Revolutionary New Approach to Breaking the Cycle of Pain and Depression (Rodale, 2014). A pioneer and leader in the field of integrative medicine, Dr. Kaplan is one of only 19 physicians in the country to be board-certified in both Family Medicine and Pain Medicine . A clinical associate professor in the Department of Community and Family Medicine at Georgetown University School of Medicine, Dr. Kaplan was one of the directors of a $1.7 million NIH grant that funded an educational initiative to incorporate complementary, alternative, and integrative medicine into Georgetown’s medical curriculum.
Dr. Kaplan has served as a consultant to NIH on multiple grant reviews committees, and contributed as an author of the Technology Assessment Statements on “The Integration of Behavioral and Relaxation Approaches into the Treatment of Chronic Pain and Insomnia” (10/1995), was a memeber of the planning committee and subject expert presenter on Acupuncture for the treatment of Osteoarthritis for the NIH Technology Assessment program on Acupuncture (11/1997)
Dr. Kaplan served on the Health and Human Services ME/CFS Advisory Committee from 2013-2017.
In 2015 Dr. Kaplan established the foundation for Total Recovery, an educational and research foundation dedicated to finding a cure for those suffering with chronic neuroinflamatory disease resulting in chronic pain, chronic fatigue and other disease states.
Dr. Yehuda Shoenfeld
Why Autoimmunity? Hyper-stimulation of the Immune System CPI and Breast Silicone Implants are Proofs of Concept
Feb 9, 2022 - 9:00 am- 9:45 am
Autoimmune diseases are induced by hyper-stimulation of the immune system ("adjuvant" ASIA Syndrome) in a genetically prone individuals, i.e. HLA-DRB1. We will describe several proofs of concepts to this hypothesis:
1) Check point inhibitor (CPI), which unleash a hyper-stimulation of the immune system leads to an emergence of avalanche of autoimmune diseases.
2) This occurs specifically in HLA-DRB1 individuals.The silicone breast implants (SBI) are also associated with autoimmune autonomic nervous system in prone individuals with HLA-DRB1 bearer.
3) Moreover, induction of the B large cell lymphoma is specifically more frequent in HLA-DRB1 individuals.
These proofs of concept support the "ASIA" (Shoenfeld's) syndrome and the mosaic of factors involved in autoimmunity (combination of hyper-stimulation of the immune system in a genetically prone individuals).
1) Discuss the controversy regarding the ASIA hypothesis
2) Understand the role of environmental factors and genetics as a potential etiology of some types of autoimmune diseases
3) Understand the hypothesized concept ASIA (Autoimmune….
4) Understand the 4 adjuvants associated believed to be responsible for triggering ASIA
Bio:
Prof. Yehuda Shoenfeld is the founder and head of the Zabludowicz Center for Autoimmune Diseases, at the Sheba Medical Center, which is affiliated to the Sackler Faculty of Medicine in Tel-Aviv University in Israel. Professor Shoenfeld’s clinical and scientific works focus on autoimmune and rheumatic diseases, and he has published more than 1750 papers in journals such as New Eng J Med, Nature, The Lancet, Proc Nat Acad Scie, J Clin Invest, J Immunol, Blood, FASEB, J Exp Med, Circulation, Cancer and others. Professor Shoenfeld is on the editorial boards of 43 journals in the fields of rheumatology and autoimmunity and is the founder and the editor of the IMAJ (Israel Medical Association Journal), the representative journal of science and medicine in the English language in Israel, and also is the founder and Editor of Autoimmunity Reviews (Elsevier) (Impact factor 7.9) and co-Editor of the Journal of Autoimmunity (Impact factor 8). For the past twenty years Yehuda has been the Editor of “Harefuah” – The Israel Journal in Medicine (Hebrew). Professor Shoenfeld received the EULAR prize in 2005, in Vienna, Austria. In UC Davis, USA, Professor Shoenfeld received the Nelson’s Prize for Humanity and Science for 2008. He was recently awarded a Life Contribution Prize in Internal Medicine in Israel, 2012 as well as the ACR Master Award in 2013.
Dr. Jonathan Kipnis
New Insights in CNS Immune Privilege
Feb 9, 2022 - 9:45 am- 10:30 am
Immune cells and their derived molecules have major impact on brain function. Mice deficient in adaptive immunity have impaired cognitive and social function compared to that of wild-type mice. Importantly, replenishment of the T cell compartment in immune deficient mice restored proper brain function. Despite the robust influence on brain function, T cells are not found within the brain parenchyma, a fact that only adds more mystery into these enigmatic interactions between T cells and the brain. Our results suggest that meningeal space, surrounding the brain, is the site where CNS-associated immune activity takes place. We have recently discovered a presence of meningeal lymphatic vessels that drain CNS molecules and immune cells to the deep cervical lymph nodes. This communication between the CNS and the peripheral immunity is playing a key role in several neurological and psychiatric disorders and, therefore, may serve as a novel therapeutic target that is worth in-depth mechanistic exploration.
Bio:
Dr. Jonathan (Jony) Kipnis is BJC Investigator, Alan A. and Edith L. Wolff Distinguished Professor of Pathology and Immunology and Professor of Neurology, Neuroscience, and Neurosurgery at Washington University in St. Louis, School of Medicine. He is also an inaugural Director of Center for Brain immunology and Glia (BIG) at Washington University. Jony graduated from the Weizmann Institute of Science in Israel, where he was a Sir Charles Clore scholar and a recipient of distinguished prize for scientific achievements awarded by the Israeli Parliament, The Knesset. Kipnis lab focuses on the complex interactions between the immune system and the central nervous system (CNS). The goal is to elucidate the cellular and molecular mechanisms underlying these interactions in neurodegenerative, neurodevelopmental, and mental disorders as well as in physiology (including healthy aging). They showed that the brain function is dependent, in part, on the function and integrity of the immune system and that immune molecules (cytokines) can play neuromodulatory roles. The fascination with immunity and its role in neurophysiology is what brought the team to a breakthrough discovery of meningeal lymphatic vessels that drain the CNS into the peripheral lymph nodes and thus serve as a physical connection between the brain and the immune system. This finding challenged the prevailing dogma of CNS being an “immune privileged organ” and opened new avenues to mechanistically study the nature of neuroimmune interactions under physiological and pathological conditions. The implications of this work are broad and range from Autism to Alzheimer’s disease through neuroinflammatory conditions, such as Multiple Sclerosis. Among other awards, Dr. Kipnis is a recipient NIH Director’s Pioneer award for 2018 to explore in more depth neuro-immune interactions in healthy and diseased brain.
Sarah Ramey- Writer and Musician
Being seen heard and respected: the patient’s dilemma and the physicians challenge
Feb 9, 2022 - 10:30 am- 11:00 am
Dr. Yehuda Shoenfeld
Post COVID-19 Syndrome, Vaccine and Autoimmunity
Feb 9, 2022 - 11:00 am- 11:45 am
Covid-19 virus is an autoimmune virus and more notorious than EBV. It induces autoimmune diseases by hyper-stimulation combined in induction of autoimmune disease with molecular mimicry.
Post COVID-19 Syndrome (PCS) is a complex of various symptoms developing a month or more after the acute phase of the disease. The cases of PCS development among patients with asymptomatic/mild forms are frequently reported; however, the pathogenesis of PCS in this group of patients is still not completely clear.
The PCS develops on average in 30–60% of patients, mainly among women.
Fatigue, shortness of breath, cough, and anosmia were reported as the most common symptoms. The possible association between the described PCS symptoms and brain damage is noted. We assume the possibility of an alternative course of COVID-19, which develops in genetically predisposed individuals with a stronger immune response, in which it predominantly affects the cells of the nervous system, possibly with the presence of an autoimmune component, which might have similarity with chronic fatigue syndrome or autoimmune dysautonomia.
We will discuss all the autoimmune ramifications of the virus, the CFS / fibromyalgia / post Covid syndrome.
Dr. Calliope Dendrou
Cross-disease Genetic and Genomic Comparisons Reveal Mechanistic and Translational Insights
Feb 9, 2022 - 11:45 am- 12:30 pm
The investigation of genetic risk profiles across common diseases has the capacity to reveal a basis of shared etiopathology and thus the potential for the development of therapeutic strategies that may benefit multiple groups of patients. Systematically identifying genetic risk profiles, however, requires the availability of population-scale cohorts coupled with extensive clinical data, and the appropriate analytical tools. We have developed a disease-agnostic approach to cluster the genetic risk profiles for >3,000 genome-wide independent loci across >19,000 disease classification codes from half a million participants in the UK Biobank, representing a large and heterogeneous population. We identify 339 distinct disease association profiles and we demonstrate how specific associations can be followed up functionally, providing a rationale for drug repositioning.
We also demonstrate how in parallel with genetic risk profile identification, high-resolution genomic profiling technologies can help to elucidate cross-disease pathophysiology, with potential implications for future drug development and precision medicine approaches to improve patient healthcare provision.
Learning outcomes:
1) Comparing genetic associations across common diseases can be informative for identifying clusters of genetic risk the correspond to shared biological pathways
2) Follow-up functional investigations can help to assess the translational potential of genetically determined pathophysiological pathways
3) High-resolution genomic profiling methods can provide further insights into shared disease mechanisms that can be exploited therapeutically
Bio
Calli received her B.Sc. from Imperial College London in 2005 (Forbes Memorial Medal Winner for Excellence in Biology), focusing on Immunology and Genetics. To further develop her interdisciplinary interest she joined the Diabetes and Inflammation Laboratory (Cambridge Institute for Medical Research) to obtain a Ph.D. under the supervision of Profs Linda Wicker and John Todd, having been awarded a Wellcome Trust studentship in Infection and Immunity. This work culminated in a seminal study showing that the immunological consequences of genome-wide association data can be dissected to inform our understanding of disease mechanisms. After completing her degree in 2009 she joined the laboratory of Prof Lars Fugger as a postdoctoral researcher to investigate how the data explosion arising from advances in genomics can be converted into clinically relevant information - in particular through comparative analyses across different diseases. To date this has led to the first study demonstrating that elucidating the functional impact of disease-associated genetic variation can have important implications for predicting clinical outcome. Calli has also won the Thomas Willis Early Career Researcher Prize in 2013 and the Oxford Multiple Sclerosis Young Investigator Award in 2014.In 2017 Calli moved to the Henry Wellcome Building of Genomic Medicine to begin her career as a PI. The key research interests of her group are to better understand the architecture of genetic predisposition across different autoimmune and immune-mediated diseases, and to explore the functional relevance and potential clinical utility of such cross-comparisons.
There are approximately 20 million people in the United Stated and millions more worldwide suffering with a wide range of conditions for which the pathophysiology is at best poorly understood. These conditions include ME/CFS, Fibromyalgia, Chronic Lyme, post covid syndrome and a number of neuropsychiatric diseases. In addition, there are millions of children struggling with PANDAS and PANS. Common to all of these conditions is significant overlapping presentations. Pathophysiological common to all of these conditions is evidence of neuroinflammation and at least in a subset of all of these conditions there is evidence for an infectious etiology and immune dysregulation. This lecture will discuss the diagnostic criteria, demographics and overlapping presentations of these conditions. The economic costs and person burden of these conditions will also be discussed. The lecture will also briefly discussa proposed definition of autoimmune encephalopathy as distinct from encephalitis.
Autoimmune diseases are induced by hyper-stimulation of the immune system ("adjuvant" ASIA Syndrome) in genetically prone individuals, i.e. HLA-DRB1. We will describe several proofs of concepts to this hypothesis:
1) Check point inhibitor (CPI), which unleashes a hyper-stimulation of the immune system leads to an emergence of avalanche of autoimmune diseases. This occurs specifically in HLA-DRB1 individuals.
2) The silicone breast implants (SBI) are also associated with autoimmune autonomic nervous system in prone individuals with HLA-DRB1 bearer.
3) Moreover, induction of the B large cell lymphoma is specifically more frequent in HLA-DRB1 individuals.
These proofs of concept support the "ASIA" (Shoenfeld's) syndrome and the mosaic of factors involved in autoimmunity (combination of hyper-stimulation of the immune system in a genetically prone individuals).
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) is a form of basal ganglia encephalitis thought to result from infection by Group A Streptococcus (GAS) and subsequent generation of autoantibodies targeting neuronal epitopes. Previous studies in my laboratory have modeled this form of autoimmune encephalitis by intranasally infecting mice with GAS. This infection results in infiltration of lymphocytes from the nose into the brain, an increase in microglial activation in the brain parenchyma and blood-brain barrier (BBB) damage, allowing for the extravasation of antibodies into the brain. Mice deficient for a transcription factor critical for Th17 lymphocyte generation do not show these pathologies in the brain after recurrent GAS infections suggesting a critical role for Th17 lymphocytes in the CNS pathology. We have recently performed single-cell RNA sequencing to characterize changes in the expression profiles of endothelial cells and microglia in mice infected with GAS. These experiments have revealed a GAS-dependent downregulation of BBB-associated endothelial markers, a loss of expression of homeostatic microglial genes and an upregulation of "disease-associated" microglial genes, including a large number of inflammatory cytokines and chemokines. These inflammatory cytokines are very similar to the ones that we have identified in the sera from children suffering from PANDAS/PANS during the acute phase of the disease. Dr. Agalliu will discuss a potential novel mechanism by which T cells in combination with activated microglia can damage the blood-brain barrier in post-infectious basal ganglia encephalitis.
Covid-19 virus is an autoimmune virus and more notorious than EBV. It induces autoimmune diseases by hyper-stimulation combined in induction of autoimmune disease with molecular mimicry.
Post COVID-19 Syndrome (PCS) is a complex of various symptoms developing a month or more after the acute phase of the disease. The cases of PCS development among patients with asymptomatic/mild forms are frequently reported; however, the pathogenesis of PCS in this group of patients is still not completely clear. The PCS develops on average in 30–60% of patients, mainly among women. Fatigue, shortness of breath, cough, and anosmia were reported as the most common symptoms. The possible association between the described PCS symptoms and brain damage is noted. We assume the possibility of an alternative course of COVID-19, which develops in genetically predisposed individuals with a stronger immune response, in which it predominantly affects the cells of the nervous system, possibly with the presence of an autoimmune component, which might have similarity with chronic fatigue syndrome or autoimmune dysautonomia. We will discuss all the autoimmune ramifications of the virus, the CFS / fibromyalgia / post Covid syndrome.
The investigation of genetic risk profiles across common diseases has the capacity to reveal a basis of shared etiopathology and thus the potential for the development of therapeutic strategies that may benefit multiple groups of patients. Systematically identifying genetic risk profiles, however, requires the availability of population-scale cohorts coupled with extensive clinical data, and the appropriate analytical tools. We have developed a disease-agnostic approach to cluster the genetic risk profiles for >3,000 genome-wide independent loci across >19,000 disease classification codes from half a million participants in the UK Biobank, representing a large and heterogeneous population. We identify 339 distinct disease association profiles and we demonstrate how specific associations can be followed up functionally, providing a rationale for drug repositioning. We also demonstrate how in parallel with genetic risk profile identification, high-resolution genomic profiling technologies can help to elucidate cross-disease pathophysiology, with potential implications for future drug development and precision medicine approaches to improve patient healthcare provision.
Dr. Joseph Bellanti
Epigenetic Factors
Feb 9, 2022 - 1:15 pm- 2:00 pm
Epigenetics is defined as those changes in gene function that occur without modifications in the basic nucleotide sequence of the DNA molecule. The applications of epigenetics to improving human health, once thought a futuristic fantasy, have now become a reality. The mechanisms of epigenetics include DNA methylation, histone modification, and non-coding RNA (ncRNA)-associated gene silencing. Epigenetic editing has the advantage of modifying and presenting DNA sequences and other DNA-binding factors that influence DNA expression without the more complex and more difficult task of gene editing that involves changing the actual DNA sequence itself. Although these approaches have not been fully implemented widely, with the immunological and autoimmune diseases, there is great potential for this, given the extensive existing data linking alterations in epigenetic states, particularly DNA methylation, with virtually every autoimmune disorder. This presentation will review the importance and relationships of epigenetics to genetic controls of the immune system in health and in disease and will offer new diagnostic and therapeutic applications for the management of the autoimmune encephalopathy disorders.
Learning Objectives:
• To review the importance and relationships of genetics and epigenetics to an understanding of the immune system in health and in disease
• To discuss the principles and mechanisms of epigenetics that underlie the autoimmune disorders
• To offer suggested diagnostic and therapeutic applications for the management of the autoimmune encephalopathy disorders.
Bio:
Dr. Bellanti is Professor of Pediatrics and Microbiology and Immunology and Director of the International Center for Interdisciplinary Studies of Immunology (ICISI) at Georgetown University Medical Center. A native of Buffalo New York, he received his MD degree from the University of Buffalo, followed by residency training at the Children’s Hospital of Buffalo, post-doctoral training in developmental immunology at the University of Florida School of Medicine, Gainesville, Florida, and viral immunology at Walter Reed Army Institute of Research (WRAIR), Washington, DC. Following military service, he was recruited at Georgetown University School of medicine as Assistant Professor of Pediatrics and Microbiology.
Dr Bellanti’s career at Georgetown represents the “triple threat” academician, proficient in teaching, research, and patient care. His investigative efforts have focused on antimicrobial research, evaluation of new vaccine strategies and developmental immunology. This work resulted in a succession of seminal research contributions including the characterization of the IgM response of the newborn, the identification of the antiviral role of secretory IgA in respiratory secretions and the cellular immune responses to viral infections following immunization or natural infection.
Soon after arriving at Georgetown, he established and became the Director of ICISI in 1975. The unique interdisciplinary strengths of the Center led to the successful award of numerous federal and private research grants, including an NIH-supported postdoctoral training program that facilitated the training of over 250 national and international postdoctoral fellows. The alumni from this program now hold leadership positions at major academic and research institutions in the US and throughout the world.
Dr. Bellanti is the recipient of numerous awards and honors, including the prestigious E. Mead Johnson Award for Research in Pediatrics, for outstanding scientific contributions, the Humanitarian Award from the American College of Allergists for “excellence and service and teaching of clinical immunology”, the Distinguished Medical Alumnus Award from the State University of Buffalo, New York and the Founder’s Day Award of Georgetown University School of Medicine. He is also the recipient of Honoris Causa degrees from the University of Palermo, Italy, Georgetown University and recently, the CEA Universidad San Pablo, Madrid, Spain.
Dr. Bellanti has also held numerous leadership positions in national and international organizations including President, Society for Pediatric Research, President, American Board of Allergy and Immunology, President, INTERASMA, President, the American College of Allergy, Asthma and Immunology (ACAAI), President, the Association of Medical Laboratory Immunologists (AMLI), and President, the American Association of Certified Allergists (ACA). Other roles include Editor-in-Chief of several journals including Pediatric Research, Annals of Allergy, Asthma & Immunology, and Allergy and Asthma Proceedings. In each of these positions, Dr. Bellanti has served with distinction and has earned the respect and esteem of his colleagues nationally and internationally.
Dr. Bellanti has published over 500 scientific articles and abstracts, as well as numerous textbook chapters and his widely acclaimed textbook in immunology. “Immunology IV: Clinical Applications in Health and Disease” which has been recently been translated to a Spanish edition, “INMUNOLOGÍA IV: Aplicaciones Clínicas en Salud y Enfermedad”.
Dr. Javier Ochoa Repáraz
Gut Microbiome and Autoimmunity
Feb 9, 2022 - 2:00 pm - 2:45 pm
Multiple sclerosis (MS) is a devastating disease of the brain and spinal cord. Neurons of MS patients are attacked by immune cells resulting in variable symptoms and disease progression patterns. One key modulator of the immune system is the gut microbiome. Recent findings indicate the existence of bidirectional and multifactorial interaction between the microbiome and the host. This intricate relationship between gut microbes and the host could significantly impact the progression of the disease.
Learning Objectives:
-
To discuss these complex interactions between gut microbes, immune cells, and the CNS in the context of MS and animal models.
-
To review existing literature on the effects of microbiome alterations on the severity and progression of the disease.
-
To consider whether the gut microbiota can be used to find new therapeutics against the disease.
Bio:
Dr. Ochoa-Repáraz received his Ph.D. in Biological Sciences (Cellular and Molecular Biology Program) from the University of Navarra in Spain. He was trained as a postdoctoral scientist at Montana State University and Dartmouth College, exploring the impact of the gut mucosal immune responses to microbes on CNS inflammatory demyelination. At Dartmouth College, he studied mechanisms of immunomodulation induced by gut symbionts and polysaccharide A (PSA) produced by Bacteroides fragilis in the context of multiple sclerosis (MS) using animal models of the disease. He has industry experience working for a large pharmaceutical company as a scientific member of their MS platform. As a faculty at EWU, he continues working on the reciprocal interaction between the gut microbiome and disease, with a specific focus on immunomodulation mediated by gut microbes and microbiome-modifying treatments in CNS demyelinating inflammation
Dr. Bruce Patterson
Diagnosis and Mechanisms of Autoimmune Encephalopathy
Feb 9, 2022 - 2:45 pm - 3:30 pm
Cytokine/Chemokine profiles have been described in a number of immune and autoimmune disorders. With the current SARS-CoV-2 pandemic, we have described specific immune signatures in both acute and in long COVID. Of widespread interest, many post-infectious chronic immune disorders share many of the same symptoms including fatigue, post-exertional malaise, and muscle/joint pain. We investigated the immune profiles in long COVID, post-vaccination long COVID, ME-CFS and Post-lyme. We found similarities in immune markers yet subtle differences in these conditions using machine learning and AI. Here, we present our immune signatures as well as possible mechanisms underlying the immune abnormalities. Further, we will present successful treatment regimens that target the specific immune abnormalities.
Bio:
Dr. Patterson received his undergraduate training in molecular biology from the University of Michigan in Ann Arbor. He then went on to Northwestern University Medical School for training in medicine. During the early stages of the AIDS epidemic, Dr. Patterson began investigating cellular reservoirs of HIV-1 using molecular and in situ technology patented in his laboratory. Dr. Patterson went on to a residency in Pathology focusing on viral pathogenesis. While in his residency, Dr. Patterson determined that enough HIV virus was present in infected individuals to account for the massive destruction of the immune system. This paradigm altering work was published in Science in 1993. Dr. Patterson later was named Chief Resident of Pathology at Northwestern Memorial Hospital. Dr. Patterson has authored over 100 manuscripts and book chapters and he continues his work on HIV-1 pathogenesis and reservoirs at Stanford University School of Medicine. Dr. Patterson was the Medical Director of Diagnostic Virology at Stanford University Hospitals and Clinics.
3:30 pm – 3:45 pm: Patients vignettes
Dr.Kim Lewis
Developing Treatments for Lyme Disease
Feb 9, 2022 - 3:45 pm - 4:30 pm
Lyme disease affects an estimated 500,000 people in the US alone, and there are approximately 2, 000,000 individuals with Chronic Lyme disease. Acute Lyme disease caused by the spirochete B. burgdorferi is treated with broad-spectrum antibiotics such as doxycycline, but about 10% of patients go on to develop a chronic disease with autoimmune disease-like symptoms overlapping with Long Covid. We find that patients with Lyme disease have an aberrant microbiome. Our animal experiments suggest that B. burgdorferi affects the gut microbiome, and in combination with broad-spectrum antibiotics that further damage the microbiome, results in a change in the immune system that leads to symptoms of a chronic disease. We are pursuing two lines of developing therapeutic interventions – a microbiome therapeutic, and a selective antibiotic to treat acute Lyme disease. We identified hygromycin A as a selective antibiotic acting against B. burgdorferi in a mouse model of infection without harming the microbiome. We expect hygromycin A to treat acute Lyme disease, preventing the development of chronic illness.
Learning Objectives:
-
Learn about the progression from acute to chronic Lyme disease
-
Learn about potential therapeutic interventions
-
Learn about the mechanism of action and properties of hygromycin A
Bio:
Kim Lewis is a University Distinguished Professor and Director, Antimicrobial Discovery Center at Northeastern University in Boston, a Fellow of the American Society of Microbiology, and a Fellow of the American Association for the Advancement of Science. He obtained his Ph.D. in Biochemistry from Moscow University, and has been on the Faculty of MIT, University of Maryland, and Tufts University prior to coming to Northeastern. Dr. Lewis is a recipient of the NIH Director’s Transformative Award and is a Clarivate highly cited researcher. He works on mechanisms of antibiotic tolerance and antibiotic discovery.
Dr. Brian Fallon
Neuropsychiatric Lyme Disease, Immune Markers and the Vagus Nerve
Feb 9, 2022 - 4:30 pm - 5:15 pm
Lyme disease can have many neuropsychiatric features, some common such as cognitive problems (brain fog, word retrieval problems, short-term memory loss), mood changes (anxiety, depression, irritability), sensory hyperarousal, and prominent fatigue, and others less common such as sensory hyperarousal (light, sound), psychosis, mania, and suicidal behaviors. This talk will present epidemiologic results from our recently published nationwide population-based cohort study examining mental disorders and suicide after Lyme disease. Immunologic findings of relevance to Lyme disease and depression will be reviewed. Finally, recent research on the benefits and risks of vagal nerve stimulation for the relief of depression, pain, and fatigue will be presented, with a special focus on its potential relevance to infection-triggered long-hauler syndromes.
Learning Objectives:
-
To describe the breadth of neuropsychiatric manifestations of Lyme disease
-
To describe immunologic findings in Lyme and depression
-
To describe the benefits and risks of vagal nerve stimulation in human disease
Bio:
Brian Fallon, MD, MPH directs the Lyme & Tick-borne Diseases Research Center at Columbia University Irving Medical Center and the Center for Neuroinflammatory and Somatic Disorders at the New York State Psychiatric Institute in New York City. As professor of clinical psychiatry, he has focused his research on Lyme disease and on clinical trials, particularly on how to help patients with persistent symptoms. His book co-authored with Dr. Jennifer Sotsky, “Conquering Lyme Disease: Science bridges the Great Divide”, was published by Columbia University Press in 2018.
Epigenetics is defined as those changes in gene function that occur without modifications in the basic nucleotide sequence of the DNA molecule. The applications of epigenetics to improving human health, once thought a futuristic fantasy, have now become a reality. The mechanisms of epigenetics include DNA methylation, histone modification, and non-coding RNA (ncRNA)-associated gene silencing. Epigenetic editing has the advantage of modifying and presenting DNA sequences and other DNA-binding factors that influence DNA expression without the more complex and more difficult task of gene editing that involves changing the actual DNA sequence itself. Although these approaches have not been fully implemented widely, with the immunological and autoimmune diseases, there is great potential for this, given the extensive existing data linking alterations in epigenetic states, particularly DNA methylation, with virtually every autoimmune disorder. This presentation will review the importance and relationships of epigenetics to genetic controls of the immune system in health and in disease and will offer new diagnostic and therapeutic applications for the management of the autoimmune encephalopathy disorders.
Cytokine/Chemokine profiles have been described in a number of immune and autoimmune disorders. With the current SARS-CoV-2 pandemic, we have described specific immune signatures in both acute and in long COVID. Of widespread interest, many post-infectious chronic immune disorders share many of the same symptoms including fatigue, post-exertional malaise, and muscle/joint pain. We investigated the immune profiles in long COVID, post-vaccination long COVID, ME-CFS and Post-lyme. We found similarities in immune markers yet subtle differences in these conditions using machine learning and AI. Here, we present our immune signatures as well as possible mechanisms underlying the immune abnormalities. Further, we will present successful treatment regimens that target the specific immune abnormalities.
Lyme disease affects an estimated 500,000 people in the US alone, and there are approximately 2, 000,000 individuals with Chronic Lyme disease. Acute Lyme disease caused by the spirochete B. burgdorferi is treated with broad-spectrum antibiotics such as doxycycline, but about 10% of patients go on to develop a chronic disease with autoimmune disease-like symptoms overlapping with Long Covid. We find that patients with Lyme disease have an aberrant microbiome. Our animal experiments suggest that B. burgdorferi affects the gut microbiome, and in combination with broad-spectrum antibiotics that further damage the microbiome, results in a change in the immune system that leads to symptoms of a chronic disease. We are pursuing two lines of developing therapeutic interventions – a microbiome therapeutic, and a selective antibiotic to treat acute Lyme disease. We identified hygromycin A as a selective antibiotic acting against B. burgdorferi in a mouse model of infection without harming the microbiome. We expect hygromycin A to treat acute Lyme disease, preventing the development of chronic illness.
Lyme disease can have many neuropsychiatric features, some common such as cognitive problems (brain fog, word retrieval problems, short-term memory loss), mood changes (anxiety, depression, irritability), sensory hyperarousal, and prominent fatigue, and others less common such as sensory hyperarousal (light, sound), psychosis, mania, and suicidal behaviors. This talk will present epidemiologic results from our recently published nationwide population-based cohort study examining mental disorders and suicide after Lyme disease.Immunologic findings of relevance to Lyme disease and depression will be reviewed.Finally, recent research on the benefits and risks of vagal nerve stimulation for the relief of depression, pain, and fatigue will be presented, with a special focus on its potential relevance to infection-triggered long-hauler syndromes.
Dr. Gary Kaplan & Organizing Committee
Welcome Notes
Feb 11, 2022 – 8:00 am – 8:15 am
8: 15 am- 8:30am: Patients vignettes
Professors Round Table: Dr. Brian Fallon, Dr. Robert Bransfield, and Dr. Craig Shimasaki
Moderator: Dr. Katz
Infections vs. Autoimmunity
Feb 11, 2022 – 8:30 am – 9:15 am
Dr. Robert Bransfield-
The Impact of Childhood Adverse Events, Chronic PTSD And the Risk of Developing Autoimmune Disease
Feb 10, 2022 - 9:15 am – 10:00 am
Childhood adverse events and chronic Posttraumatic Stress Disorder (PTSD) results in chronic stress that is associated with compromised immunocompetency that may be associated with persistent inflammation, autoimmunity and a failure of adaptive immunity. Chronic infectious encephalopathies can result in temporal lobe inflammation associated with intrusive symptoms. Intrusive symptoms are a core component of PTSD pathophysiology and result in hyperarousal, avoidance and emotional numbing. Intrusive symptoms can be associated with a high level of distress, and sometimes suicide and aggressive behavior. Having a complex, invisible illness, such as Autoimmune Encephalopathy Secondary to Infectious Disease (AEIE) can be quite traumatic, especially when oneself, family, friends, medical providers, and insurance companies have difficulty comprehending and accepting this causal association. Therefore there is a reciprocal causal relationship between PTSD and AEIE. It is important to recognize this pathophysiology in patients and to consider treatment options. Treatments directed towards reducing intrusive symptoms include topiramate, prazosin, cyproheptadine, and anti-obsessive medications.
Learning Objectives:
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To review the pathophysiology of the reciprocal association between AEIE and Intrusive Symptoms and Posttraumatic Stress Disorder.
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To review the assessment of patients with AEIE and intrusive symptoms and Posttraumatic Stress Disorder.
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To review the treatment options for Posttraumatic Stress Disorder associated with AEIE.
Bio:
Dr. Robert C. Bransfield, MD, DLFAPA is a graduate of Rutgers College and the George Washington University School of Medicine. He completed his psychiatric residency training at Sheppard and Enoch Pratt Hospital, is board certified by the American Board of Psychiatry and Neurology in Psychiatry and is a Distinguished Life Fellow of the American Psychiatric Association. Dr. Bransfield’s primary activity is an office based private practice of psychiatry. In addition, Dr Bransfield is the Past President of ILADS, the International Lyme and Associated Diseases Educational Foundation and the New Jersey Psychiatric Association. He has held a number of administrative positions with organizations involved with health, mental health and community related activities. He is a Clinical Associate Professor of Psychiatry at Rutgers—Robert Wood Johnson Medical School. Dr Bransfield has authored and co-authored a number of publications in peer-reviewed literature, other medical publications and books; has been active in political advocacy on an international, national, state and local level
Dr. Susan Swedo
PANS/PANDAS- Post-infectious Basal Ganglia Encephalopathies
Feb 10, 2022 - 10:00 am – 10:45 am
The unique clinical characteristics of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS) were first identified more than three decades ago in a cohort of young children with unusually abrupt onset of obsessive-compulsive disorder (OCD) and tics following Group A streptococcal (GAS) infections. PANDAS was postulated to occur when the molecular mimicry of infecting GAS bacteria provokes production of antibodies that misrecognize basal ganglia antigens as foreign and incite a neuroinflammatory response manifesting as a constellation of neurologic, emotional, behavioral, and cognitive symptoms. Additional factors, such as T-cell activation, have also been shown to play a role, documenting that PANDAS is indeed an “Autoimmune Encephalopathy Secondary to Infectious Disease”. In addition to presenting a summary of the PANDAS research database, the presentation will provide an overview of the clinical presentation, diagnostic evaluation, treatment and management of PANDAS and PANS (Pediatric Acute-onset Neuropsychiatric Syndrome – clinically comparable to PANDAS but lacking a GAS infection trigger).
Learning Objectives:
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Identify the clinical presentation of PANS/PANDAS
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Describe timely and appropriate strategies for evaluation of acute-onset symptomatology
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Utilize on-line resources to develop plans for acute and long-term management of PANS/PANDAS cases
Bio:
Dr. Swedo received her B.A. degree from Augustana College in 1977 and her M.D. from Southern Illinois University in 1980. Shortly after completing a residency in pediatrics at Northwestern University in Chicago, Illinois, Dr. Swedo was named Chief of the Division of Adolescent Medicine at the University. The following year, she moved to Washington D.C. and became a senior staff fellow in the Child Psychiatry Branch, NIMH. Dr. Swedo was granted tenure in 1992, became Head of the Section on Behavioral Pediatrics in 1994, and Chief of the Pediatrics and Developmental Neuropsychiatry Branch in 1998. She also served as the Acting Scientific Director for NIMH from 1995 through 1998. Dr. Swedo recently received the Joel Elkes International Research Award from the American College of Neuropsychopharmacology. Her laboratory studies childhood-onset obsessive compulsive disorder and related disorders, including Tourette syndrome and Sydenham chorea.
10:45 am- 11:00 am: Patients vignettes
Dr. Yehuda Shoenfeld-
Helminthes Based Derivative to Treat Autoimmunity: TPC a Bi-functional Immunomodulatory Future
Feb 10, 2022 – 11:00 am – 11:45 am
Where there are helminthes , autoimmunity is rare. The aim of the helminthes is to protect themselves via immunomodulation of the host immune network. We have constructed a bi-functional compound consists of phosporylcholine-tuftsin (TPC). The aim was to prove its immunomodulatory function in murine models of autoimmune diseases and in ex-vivo human models. We introduced TPC to murine models of autoimmune diseases such as lupus NZBxW/F1 mice, collagen-induced-arthritis (CIA), dextransulfatsodiumsalt (DSS) induced colitis, experimental-autoimmune-encephalomyelitis (EAE) and showed its cytokines production and Tregulatory profile. Ex-vivo using human peripheral-mononuclear-cells (PBMCs) or biopsies from patients with giant-cell-arteritis (GCA) and lupus were analyzed for cytokines production.
TPC attenuated the clinical score of murine autoimmune models of lupus CIA, DSS-induced-colitis and EAE . TPC decreased significantly the secretion of inflammatory cytokines (TNFIL-1, IL-6, IFN and enhanced production of anti-inflammatory IL-10, expanded T and B regulatory cells. Likewise, TPC had an equal effect as methylprednisolone in a mouse model of lupus, inhibiting disease development in established lupus. Furthermore, The immunomodulatory activity of TPC was proven also ex-vivo in lupus and GCA reducing the inflammatory cytokines production by patients PBMCs and in biopsies from GCA.
The bi-functional immunomodulatory activity of TPC was attributed to: a) The PC part which inhibited significantly TLR4 expression by HEKTM-mTLR4 cells, through NFkB expression; b) TPC shifts macrophage cells from pro-inflammatory macrophages M1 to anti-inflammatory M2-secreting IL-10 and induce Tregs through the neuropilin-1. Our data propose the potential novel therapy to treat autoimmune condition.
Dr. Ru-Rong Ji
Central Immune Dysregulation in Chronic Pain Syndromes
Feb 10, 2022 – 11:45 am – 12:30 pm
Chronic pain affects 30% Americans and occurs after arthritis, nerve injury, and infections.
Chronic pain is induced and maintained by neural plasticity in the CNS (central sensitization). Accumulating evidence suggests that neuroinflammation drives chronic and widespread pain. A characteristic feature of neuroinflammation is the activation of glial cells, such as microglia and astrocytes, in the spinal cord and brain, leading to the release of proinflammatory cytokines and chemokines. Glia-produced cytokines and chemokines are powerful neuromodulators and play a sufficient role in inducing pain-like symptoms such as hyperalgesia and allodynia. Specialized pro-resolving mediators (SPMs), such as resolvins and protectins, produced during the resolution phase of inflammation, are potent inhibitors of pain. SPMs control pain via neuro-immune modulation.
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Attendees will learn that neuroinflammation in the CNS drives chronic and widespread pain through neuro-immune interactions.
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Chronic pain could be a result of “gliopathy”, i.e. dysregulation of glial cells.
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Activation of glial cells such as microglia and astrocytes results in the development of chronic pain through inflammatory cytokines and chemokines.
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Specialized pro-resolving mediators (SPMs) are potent inhibitors of pain through neuro-immune modulation.
Bio:
Ru-Rong Ji, PhD, is the chief of pain research within Duke Anesthesiology, co-director of the Center for Translational Pain Medicine, and a professor of anesthesiology and neurobiology. As director of the Sensory Plasticity and Pain Research Laboratory at Duke, his research focuses on molecular and cellular mechanisms of chronic pain, such as inflammatory pain, neuropathic pain, and cancer pain. He is internationally-recognized for his contributions to demonstrating critical roles of MAP kinase signaling pathways and glial cells in the pathogenesis of chronic pain. His recent work has demonstrated powerful antinociceptive actions of pro-resolution lipid mediators (e.g., resolvins). Ji lectures internationally and reviews papers for numerous international journals. He also serves on National Institutes of Health review panels and the editorial boards of Pain, Neuroscience, and Neuroscience Bulletin. He previously was an associate professor at Brigham and Women’s Hospital, Harvard Medical School, before joining the Duke faculty in 2012. He earned a PhD in neurobiology at Shanghai Institute of Physiology and completed postdoctoral training at Peking (Beijing) University Medical School, Karolinska Institute, and Johns Hopkins University School of Medicine.
Childhood adverse events and chronic Posttraumatic Stress Disorder (PTSD) results in chronic stress that is associated with compromised immunocompetency that may be associated with persistent inflammation, autoimmunity and a failure of adaptive immunity. Chronic infectious encephalopathies can result in temporal lobe inflammation associated with intrusive symptoms. Intrusive symptoms are a core component of PTSD pathophysiology and result in hyperarousal, avoidance and emotional numbing. Intrusive symptoms can be associated with a high level of distress, and sometimes suicide and aggressive behavior. Having a complex, invisible illness, such as Autoimmune Encephalopathy Secondary to Infectious Disease (AEIE) can be quite traumatic, especially when oneself, family, friends, medical providers, and insurance companies have difficulty comprehending and accepting this causal association. Therefore there is a reciprocal causal relationship between PTSD and AEIE. It is important to recognize this pathophysiology in patients and to consider treatment options. Treatments directed towards reducing intrusive symptoms include topiramate, prazosin, cyproheptadine, and anti-obsessive medications.
The unique clinical characteristics of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS) were first identified more than three decades ago in a cohort of young children with unusually abrupt onset of obsessive-compulsive disorder (OCD) and tics following Group A streptococcal (GAS) infections. PANDAS was postulated to occur when the molecular mimicry of infecting GAS bacteria provokes production of antibodies that misrecognize basal ganglia antigens as foreign and incite a neuroinflammatory response manifesting as a constellation of neurologic, emotional, behavioral, and cognitive symptoms.Additional factors, such as T-cell activation, have also been shown to play a role, documenting that PANDAS is indeed an “Autoimmune Encephalopathy Secondary to Infectious Disease”.In addition to presenting a summary of the PANDAS research database, the presentation will provide an overview of the clinical presentation, diagnostic evaluation, treatment and management of PANDAS and PANS (Pediatric Acute-onset Neuropsychiatric Syndrome – clinically comparable to PANDAS but lacking a GAS infection trigger).
Chronic pain affects 30% Americans and occurs after arthritis, nerve injury, and infections.
Chronic pain is induced and maintained by neural plasticity in the CNS (central sensitization). Accumulating evidence suggests that neuroinflammation drives chronic and widespread pain. A characteristic feature of neuroinflammation is the activation of glial cells, such as microglia and astrocytes, in the spinal cord and brain, leading to the release of proinflammatory cytokines and chemokines. Glia-produced cytokines and chemokines are powerful neuromodulators and play sufficient role in inducing pain-like symptoms such as hyperalgesia and allodynia. Specialized pro-resolving mediators (SPMs), such as resolvins and protectins, produced during the resolution phase of inflammation, are potent inhibitors of pain. SPMs control pain via neuro-immune modulation.
Dr.Otávio Cabral Marques
Systems Immunology of COVID-19: Shedding New Light on Unanswered Questions
Feb 10, 2022 – 1:15 pm – 2:00 pm
We aimed to employ an integrative systems immunology approach to gain novel insights into the immunopathology of the coronavirus disease 2019 (COVID-19). For instance, we investigated why the COVID-19 fatality rate varies by sex and age as well as we assessed autoantibody network signatures that are associated with SARS-CoV-2 infections. Our work suggests specific immune-regulatory pathways associated with sex and age of patients infected with SARS-CoV-2 and provides a possible link between the inverse modulation of cytokine/chemokine and neutrophil transcriptional signatures. This point out the existence of specific immune-regulatory pathways underlying the sexual dimorphism of COVID-19 morbidity and mortality. Furthermore, our data also indicate that autoantibodies targeting G protein-coupled receptors (GPCRs), renin-angiotensin system (RAS)-related molecules, and autoantibodies linked to classic autoimmune diseases associate with clinical outcomes of COVID-19 patients. These molecules represent potential new clinically relevant biomarkers that predict COVID-19 severity. There is an increasing disruption of autoantibody network signatures moving from patients with mild, to moderate and finally severe disease. This suggests a gradual loss of autoantibody homeostasis that accompanies the progression of COVID-19 triggered by the SARS-CoV-2-induced immune dysregulation. Taken together, work opens new avenues to improve diagnostic and therapeutic options of COVID-19 patients, providing new insights for a better clinical management of these individuals.
Bio:
Otávio Cabral-Marques is an Associated Scientist at the Department of Immunology/Institute of Biomedical Sciences and the Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, both at the University of São Paulo. Biologist (2001-2005), He obtained his MSc (2006-2008) and PhD (2008-2012) degrees from the Institute of Biomedical Sciences - University of São Paulo (USP), performing his Sandwich PhD (Dec, 2010 - May, 2011) at the University of Washington/Seattle Children's Research Institute, USA. Otávio performed his Post-doctorate in Brazil (USP: 2012 - 2015) and Germany (University of Lubeck, Oct, 2015 - April, 2018; University of Freiburg: Apr, 2015 - Nov, 2019). Otavio is the Brazilian Junior Ambassador of the Universal Scientific Education and Research Network (USERN).
Dr. Mark Opp
Sleep, Host Defense, Chronic Viral Infections and Fatigue
Feb 10, 2022 – 2:00 pm – 2:45 pm
“Sickness behavior” is an adaptive response of the host organism to infection. Invasion by a pathogen elicits complex responses by the host organism’s immune system. These immune responses actively alter physiology and behavior in a manner that collectively functions to inhibit replication of the pathogen, clear the pathogen from the host, and return the organism to health.
Much is now known of the mechanisms underlying sickness behavior. Cytokines are key components of the innate immune system that function as critical intracellular messengers. Cytokines and their receptors are present in normal, healthy brain, in the absence of immune challenge. In brain, cytokines contribute to the regulation/modulation of multiple physiological processes and behaviors, including but not limited to: arousal state; thermoregulation; appetite and feeding; sexual behavior; social exploration; and mood. Each of these aforementioned behaviors and physiological processes are altered during sickness behavior and represent dimensions of fatigue. Among the many cytokines, chemokines and growth factors that have been implicated in the regulation/modulation of sleep and sickness behavior, interleukin (IL)-1, IL-6, and tumor necrosis factor-α _(TNF) are the most widely studied.
Pre-clinical models can be used to mechanistically study fatigue. One advantage of pre-clinical models is that fatigue may be operationally defined and in relatively simple terms. For example, definitions of fatigue in rodents distinguish between obligatory behaviors, such as feeding and drinking that are essential for survival, and facultative behaviors, such as wheel running, which are voluntary and not essential for survival. One pre-clinical model that meets these criteria is infection of mice with murine gamma-herpesvirus 68 (γHV68). There are two phases to infection with γHV68: acute, active infection in the lung, and chronic, latent infection in the spleen, lymph nodes and bone marrow. The impact of infection of mice with γHV68 on physiology and behavior differs between the acute infectious period in the lung and chronic infection in the spleen. This model has functional utility for the study of chronic viral infections as contributors to the etiology of fatigue.
Learning Objectives: At the conclusion of this talk, attendees should …
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Recognize that there are bidirectional links between sleep and host defense.
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Identify characteristics of model systems that are useful in studies of fatigue.
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Describe the role of chronic viral infections in the etiology of fatigue.
Bio:
Dr. Opp is Professor of physiology and Director of the Sleep and Inflammation Laboratory in the Department of Integrative Physiology at the University of Colorado Boulder (UCB). He received his PhD in Zoology from Washington State University 1987, and after post-doctoral training at the University of Tennessee Memphis, he obtained an Assistant Professor faculty appointment in the Department of Psychiatry & Behavioral Sciences at the University of Texas Medical Branch, Galveston, TX. He was appointed Professor in the Department of Anesthesiology at the University of Michigan, Ann Arbor, MI; served as Vice Chair for Basic Research and Director of Grants Administration in the Department of Anesthesiology & Pain Medicine at the University of Washington, Seattle, WA; and just completed a term as Chair of the Department of Integrative Physiology at UCB. Dr. Opp’s research programs aim to elucidate sleep-immune interactions, specifically the role of chronic insufficient sleep in inflammatory disease. Current projects use mouse models to determine mechanisms by which sleep disruption contributes to sequelae of traumatic brain injury, Alzheimer’s disease pathogenesis, and to the etiology of musculoskeletal pain. Dr. Opp has been continuously funded by NIH for more than 30 years; has published more than 120 peer-reviewed primary data papers; and has mentored numerous undergraduate and graduate students, post-doctoral fellows, interns and residents. Dr. Opp’s contributions to the field include serving as president of the Sleep Research Society and president of the PsychoNeuroImmunology Research Society. In addition, he was the founding chair of the first Gordon Conference of Sleep Regulation and Function, and the founding editor-in-chief of the Elsevier journal Neurobiology of Sleep and Circadian Rhythms.
Dr. Hakima Amri
Using Phylogenetics to Map Disease Heterogeneity and Treatment Outcome
Feb 10, 2022 – 2:45 pm – 3:30 pm
The approach to diagnosing and treating patients is based on physician evaluation of the clinical presentation and the associated symptoms. However, the picture thus obtained is often incomplete for effective treatment as the pathophysiology of complex diseases involves a complex interplay of mechanisms at the cellular and molecular levels. This inherent complexity is compounded by heterogeneity within and between patients and their molecular diversity, which is influenced by intrinsic and extrinsic factors.
In recent years we have seen significant biomedical advancements in identifying genetic, epigenetic, and metabolic contributors to disease processes, but powerful tools that can provide a blueprint for a comprehensive assessment of disease manifestation in individual patients and for prediction of disease outcomes as well as responses to treatment are needed. A major shortcoming of current efforts to develop such sophisticated analytical tools is the absence of methods for stratification of patients according to their susceptibility to developing disease, their sensitivity to internal or external insults, their tolerability of various therapies, and their differential response to treatment. We have developed a method using the evolution-based approach of phylogenetics to analyze high-throughput data allowing stratification of patients based on their shared derived molecular traits, and then grouping them in their respective phyletic clades (or populations). We selected cancer, a highly complex inflammatory disease, to illustrate the proof-of-concept using omics data.
Knowing the phyletic clade of the patient will provide physicians with an informed basis for developing a more efficacious treatment plan, prescribing target-directed drugs or other therapies, and supervising the course of treatment by monitoring the patient’s progress on a dynamic evolutionary tree. This approach applies personalized medicine with systems biology-based precision.
Bio:
Hakima Amri is Professor of Biochemistry and Physiology at Georgetown University in the Department of Biochemistry and Cellular and Molecular Biology. She completed her undergraduate education in Developmental Biology at the University of Constantine, Algeria and her graduate studies at Pierre and Marie Curie-Sorbonne University, in Paris, France. There, she earned a Master’s of Science degree in Reproductive Biology and a Ph.D. in Steroid Biochemistry. After moving to the United States, she joined the Georgetown University Faculty where she co-founded the Integrative Medicine educational initiative. Dr. Amri’s research focuses on understanding the action mechanism of disease processes using comprehensive systems biology approaches. She investigates changes of biomarkers profiles from healthy to disease states and identifies bio-signatures using big data. Her research is enhanced by a novel analytical approach she recently developed in collaboration with her colleagues. This novel method translates omics data– from genomics, proteomics and metabolomics high throughput analysis into molecular signatures that are presented in a multidimensional, dynamic model highly suited for precision medicine. Dr. Amri is currently engaged in converting this method into a cost effective and noninvasive diagnostic tool. Her work is supported by a patent granted by the United States Patents Office. As the lead inventor of the technology and a co-founder of the newly launched Start Up, Valor Diagnostics, Dr. Amri serves as the Chief Science Officer
3:30pm – 3:45pm: Patients vignettes
Dr. Harald Heidecke
Antibodies against G-Protein-Coupled-Receptors in acute and long COVID-19
Feb 10, 2022 – 3:45 pm – 4:30 pmMyalgic Encephalomyelitis or Chronic Fatigue Syndrome (CFS/ME) is a complex and severely disabling disease with a prevalence of 0.3% and no approved treatment
and therefore a very high medical need. Following an infectious onset patients suffer from severe central and muscle fatigue, chronic pain, cognitive impairment, and
immune and autonomic dysfunction. We founddescribed for the first time elevated ß2 adrenergic receptor (ß2AdR) and M3 acetylcholine receptor antibodies in a
subset of CFS/ME patients.
A subset of long COVID patients suffers from debilitating fatigue and exertion intolerance referred to as Post COVID Syndrome (PCS) of whom a subset fulfills diagnostic
criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Our data indicate that the relationship between autoantibodies targeting GPCRs and RAS-related molecules associates with the clinical severity of COVID-19, suggesting
novel molecular pathways for therapeutic interventions.
Bio:
Dr. Harald Heidecke, PhD, studied Chemistry at the Julius-Maximilians University Würzburg and Pharmacy at the Free University Berlin. He wrote his PhD thesis in pharmaceutical biochemistry at the Free University Berlin. In 1998 he founded the CellTrend GmbH and is this then the owner and chief executive officer (CEO) of CellTrend. The main focus of CellTrend is the determination of antibodies against G-Protein-Coupled-Receptors (GPCR). CellTrend has a Quality managment system. CellTrend is strictly adhere to the rules of Good Manufacture Practice (GMP, FDA).
Dr. Craig Shimasaki
Molecular Mimicry and Infections: A Biological Mechanism for Autoimmune Encephalitis, Antineuronal Antibodies, and Neuronal Cell Stimulation Associated with Neurologic Lyme, PANS/PANDAS and Long-COVID
Feb 10, 2022 – 4:30 pm – 5:15 pm
Neuropsychiatric disorders are complex, and their symptoms can result from diverse etiologies such as genetic, trauma, metabolic, environmental and others. There is a growing body of evidence that portions of neuropsychiatric disorders arise from autoimmune dysfunction. Neuropsychiatric disorders that arise from autoimmune and/or neuroinflammatory conditions of the brain and central nervous system include N-methyl-D-aspartate receptor (NMDAR), glutamic acid decarboxylase 65 (GAD65), dopamine-2 receptor (D2R) and others. These have been shown to result from autoantibodies directed against various biological targets such as extracellular antigens, neuronal cell surface proteins and ion channels, resulting in neuropsychiatric symptoms such as obsessive-compulsive disorders (OCD), anxiety, repetitive behaviors, psychosis, delusions, sleep disturbances and many others.
The immune system protects us from invading organisms, but through dysfunction it also contributes to chronicity of disease that can result in neuropsychiatric disorders in patients infected by Lyme, strep, babesia and other microbes such as SARS-CoV-2. The objective of this presentation is to provide a basic understanding of molecular mimicry and why certain infectious organisms tend are repeatedly identified in patients with autoimmune encephalopathy, secondary to these infections. We will review the biological mechanism of molecular mimicry and its connection to autoimmune dysfunction, producing autoantibodies directed against self-proteins, resulting in many of the symptoms described. A brief overview of several infection-triggered neuropsychiatric disorders will serve as a medical model for these conditions. Data will be presented from published case studies examining autoantibodies and their correlation with various neuropsychiatric disorders, as well as an overview of current research that may lead to more effective targeted therapies for immune-mediated neuropsychiatric disorders.
Learning Objectives:
At the conclusion of this presentation, the participant will be able to:
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Explain the basic concepts of molecular mimicry and the process that leads to cross-reactive autoimmune antibodies directed against targets in the brain.
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Describe why certain infectious organisms are repeatedly identified in patients suffering from autoimmune encephalopathies, secondary to infectious disease.
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Assess the appropriate application and use of anti-neuronal antibody testing in the diagnosis and treatment of patients presenting with symptoms of autoimmune encephalopathy, secondary to infectious disease.
Bio:
Craig Shimasaki is co-founder and CEO of Moleculera labs, a neuroimmunology precision medicine company focused on identifying underlying roots of neurologic, psychiatric, and behavioral disorders triggered by an autoimmune response. The company’s research and clinical testing is focused on the molecular mimicry of common infections, and how they trigger autoimmune antibodies resulting in chronic and debilitating disorders of the brain, heart and immune system. The company’s blood testing panel is based on research from Dr. Madeleine Cunningham’s laboratory at the University of Oklahoma Health Sciences Center. Research has led to the identification of autoantibodies against targets associated with post-infectious neuropsychiatric sequalae such as dopamine D1, dopamine D2 receptors, autoantibodies directed against lysoganglioside GM1 and tubulin, as well as neuronal cell stimulatory activity of calcium-dependent calmodulin kinase II (CaMKII) simulating brain neurotransmitters.
Shimasaki received his BS in Biochemistry from University of California at Davis, his PhD in Molecular Biology from the University of Tulsa, and his MBA from Northwestern University, Kellogg School of Business. He an Adjunct Professor at the University of Oklahoma. His passion is to help translate scientific and medical discoveries into acutely needed products so that more patients can live healthier lives.
We aimed to employ an integrative systems immunology approach to gain novel insights into the immunopathology of the coronavirus disease 2019 (COVID-19). For instance, we investigated why the COVID-19 fatality rate varies by sex and age as well as we assessed autoantibody network signatures that are associated with SARS-CoV-2 infections. Our work suggests specific immune-regulatory pathways associated with sex and age of patients infected with SARS-CoV-2 and provides a possible link between the inverse modulation of cytokine/chemokine and neutrophil transcriptional signatures. This point out the existence of specific immune-regulatory pathways underlying the sexual dimorphism of COVID-19 morbidity and mortality. Furthermore, our data also indicate that autoantibodies targeting G protein-coupled receptors (GPCRs), renin-angiotensin system (RAS)-related molecules, and autoantibodies linked to classic autoimmune diseases associate with clinical outcomes of COVID-19 patients. These molecules represent potential new clinically relevant biomarkers that predict COVID-19 severity. There is an increasing disruption of autoantibody network signatures moving from patients with mild, to moderate and finally severe disease. This suggests a gradual loss of autoantibody homeostasis that accompanies the progression of COVID-19 triggered by the SARS-CoV-2-induced immune dysregulation. Taken together, work opens new avenues to improve diagnostic and therapeutic options of COVID-19 patients, providing new insights for a better clinical management of these individuals.
“Sickness behavior” is an adaptive response of the host organism to infection. Invasion by a pathogen elicits complex responses by the host organism’s immune system. These immune responses actively alter physiology and behavior in a manner that collectively functions to inhibit replication of the pathogen, clear the pathogen from the host, and return the organism to health.
Much is now known of the mechanisms underlying sickness behavior. Cytokines are key components of the innate immune system that function as critical intracellular messengers. Cytokines and their receptors are present in normal, healthy brain, in the absence of immune challenge. In brain, cytokines contribute to the regulation/modulation of multiple physiological processes and behaviors, including but not limited to: arousal state; thermoregulation; appetite and feeding; sexual behavior; social exploration; and mood. Each of these aforementioned behaviors and physiological processes are altered during sickness behavior and represent dimensions of fatigue. Among the many cytokines, chemokines and growth factors that have been implicated in the regulation/modulation of sleep and sickness behavior, interleukin (IL)-1, IL-6, and tumor necrosis factor-α _(TNF) are the most widely studied.
Pre-clinical models can be used to mechanistically study fatigue. One advantage of pre-clinical models is that fatigue may be operationally defined and in relatively simple terms. For example, definitions of fatigue in rodents distinguish between obligatory behaviors, such as feeding and drinking that are essential for survival, and facultative behaviors, such as wheel running, which are voluntary and not essential for survival. One pre-clinical model that meets these criteria is infection of mice with murine gamma-herpesvirus 68 (γHV68). There are two phases to infection with γHV68: acute, active infection in the lung, and chronic, latent infection in the spleen, lymph nodes and bone marrow. The impact of infection of mice with γHV68 on physiology and behavior differs between the acute infectious period in the lung and chronic infection in the spleen. This model has functional utility for the study of chronic viral infections as contributors to the etiology of fatigue.
The approach to diagnosing and treating patients is based on physician evaluation of the clinical presentation and the associated symptoms. However, the picture thus obtained is often incomplete for effective treatment as the pathophysiology of complex diseases involves a complex interplay of mechanisms at the cellular and molecular levels. This inherent complexity is compounded by heterogeneity within and between patients and their molecular diversity, which is influenced by intrinsic and extrinsic factors.
In recent years we have seen significant biomedical advancements in identifying genetic, epigenetic, and metabolic contributors to disease processes, but powerful tools that can provide a blueprint for a comprehensive assessment of disease manifestation in individual patients and for prediction of disease outcomes as well as responses to treatment are needed. A major shortcoming of current efforts to develop such sophisticated analytical tools is the absence of methods for stratification of patients according to their susceptibility to developing disease, their sensitivity to internal or external insults, their tolerability of various therapies, and their differential response to treatment. We have developed a method using the evolution-based approach of phylogenetics to analyze high-throughput data allowing stratification of patients based on their shared derived molecular traits, and then grouping them in their respective phyletic clades (or populations). We selected cancer, a highly complex inflammatory disease, to illustrate the proof-of-concept using omics data.
Knowing the phyletic clade of the patient will provide physicians with an informed basis for developing a more efficacious treatment plan, prescribing target-directed drugs or other therapies, and supervising the course of treatment by monitoring the patient’s progress on a dynamic evolutionary tree. This approach applies personalized medicine with systems biology-based precision.
Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (CFS/ME) is a complex and severely disabling disease with a prevalence of 0.3% and no approved treatment and therefore a very high medical need. Following an infectious onset patients suffer from severe central and muscle fatigue, chronic pain, cognitive impairment, and immune and autonomic dysfunction. We found and described for the first time elevated ß2 adrenergic receptor (ß2AdR) and M3 acetylcholine receptor antibodies in a subset of CFS/ME patients.
A subset of long COVID patients suffers from debilitating fatigue and exertion intolerance referred to as Post- COVID Syndrome (PCS) of whom a subset fulfills diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Our data indicate that the relationship between autoantibodies targeting GPCRs and RAS-related molecules are associated with the clinical severity of COVID-19, suggesting novel molecular pathways for therapeutic interventions.
Neuropsychiatric disorders are complex, and their symptoms can result from diverse etiologies such as genetic, trauma, metabolic, environmental and others. There is a growing body of evidence that portions of neuropsychiatric disorders arise from autoimmune dysfunction. Neuropsychiatric disorders that arise from autoimmune and/or neuroinflammatory conditions of the brain and central nervous system include N-methyl-D-aspartate receptor (NMDAR), glutamic acid decarboxylase 65 (GAD65), dopamine-2 receptor (D2R) and others. These have been shown to result from autoantibodies directed against various biological targets such as extracellular antigens, neuronal cell surface proteins and ion channels, resulting in neuropsychiatric symptoms such as obsessive-compulsive disorders (OCD), anxiety, repetitive behaviors, psychosis, delusions, sleep disturbances and many others.
The immune system protects us from invading organisms, but through dysfunction it also contributes to chronicity of disease that can result in neuropsychiatric disorders in patients infected by Lyme, strep, babesia and other microbes such as SARS-CoV-2. The objective of this presentation is to provide a basic understanding of molecular mimicry and why certain infectious organisms tend to be repeatedly identified in patients with autoimmune encephalopathy, secondary to these infections. We will review the biological mechanism of molecular mimicry and its connection to autoimmune dysfunction, producing autoantibodies directed against self-proteins, resulting in many of the symptoms described. A brief overview of several infection-triggered neuropsychiatric disorders will serve as a medical model for these conditions. Data will be presented from published case studies examining autoantibodies and their correlation with various neuropsychiatric disorders, as well as an overview of current research that may lead to more effective targeted therapies for immune-mediated neuropsychiatric disorders.
Dr. Gary Kaplan & Organizing Committee
Welcome Notes
Feb 11, 2022 – 8:00 am – 8:15 am
8: 15 am- 8:30am: Patients vignettes
Professors Round Table: Dr. Kim Lewis, Dr. Joseph Bellanti, and Dr. Bruce Patterson
Moderator: Dr. Kaplan
Feb 11, 2022 – 8:30 am – 9:15 am
Dr. Robert Bransfield -
Treatments for Sleep Disorders and Psychological Manifestations of Autoimmune Encephalopathy Secondary to Infectious Disease
Feb 11, 2022 – 9:15 am – 10:00 am
Sleep disorders acquired as a result of autoimmune encephalopathy (AEID) secondary to infectious disease are quite significant and include insomnia (early, mid, late), non-restorative sleep, restless leg, paroxysmal nocturnal leg movements, sleep apnea (obstructive and central), nightmares, circadian rhythm shift and narcolepsy (with sleep attacks, cataplexy, sleep paralysis and hypnagogic hallucinations). Poor sleep quality is associated with impaired immunocompetence and contributes to disease progression. Identifying, categorizing and treating the sleep disorders associated with AEID is a critical component of treatment and improves immunocompetence.
Psychiatric manifestations acquired as a result of AEID are also quite significant. The causal association between Late Stage Lyme Disease and Post-Acute COVID-19 Sequelae has been well studied and are quite representative of the symptoms seen in chronic immune mediated psychiatric symptoms. Common symptoms include impaired attention span, brain fog, unfocused concentration, joint symptoms, depression, anxiety disorders, decreased frustration tolerance, working memory impairments, decreased functional capacity, short-term memory impairments, difficulty prioritizing multiple tasks, fatigue, non-restorative sleep, multitasking difficulties, sudden mood swings, hypersomnia, mental apathy, insomnia, tingling, word finding difficulties, name retrieval, headaches, sound hypersensitivity, paresis, anhedonia, depersonalization, cold intolerance, body temperature fluctuations, light sensitivity, sensory overload, and dysfluent speech. Treating these symptoms facilitates recovery.
Learning Objectives:
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To recognize and understand the pathophysiology that occurs when AEID results in sleep disorders and psychiatric symptoms that lead to disease progression.
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To be able to assess and diagnose sleep disorders and psychiatric symptoms associated with AEID.
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To understand the treatment options and treatment strategies that are available to treat sleep disorders and psychiatric symptoms seen in patients with AEID.
Dr. Amiram Katz
Treatment for Autoimmune Encephalopathy Secondary to Infectious Disease - Lessons Learned from Lyme Disease
Feb 11, 2022 – 10:00 am – 10:45 am
It is estimated that about 10-20% of patients who contract Lyme disease will develop a chronic illness of autoimmune nature, some with symptoms consistent with AEIE. This can happen even if the infection is treated appropriately and in a timely manner. We named the neuropsychiatric condition that develops after Lyme disease - ANDAL (Autoimmune Neuropsychiatric Disorder Associated with Lyme disease).
Demonstrating antibodies targeting different cerebral antigens confirms the autoimmune nature of this condition and supports immuno-modulatory treatment approaches.
Discontinuing all anti-microbial agents and initiating weekly Intramuscular Benzathine Penicillin-G, 600,000 -1,200,000 Million units, can results in dramatic improvement within a few weeks of treatment in some patients.
If there are prominent neuropathic symptoms or if there is no response to Benzathine Penicillin -G, immunoglobulins, intravenously or subcutaneously are prescribed. Other immune modulatory approaches as well as correcting cytokines imbalance will be discussed.
Learning Objectives:
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To recognize ANDAL (autoimmune neuropsychiatric disorder associated with Lyme Disease)
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To learn how Low Dose Penicillin can alleviate most ANDAL symptoms in some patients
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Immunoglobulins are the safest immune modulatory treatment for AEIE especially when the eradication of the underlying infection is not certain
Bio:
Amiram Katz, a Board-Certified Neurologist, practices at MedAhead Inc. where he sees patients with protracted tick-borne diseases among other neurologically compromised patients. He was recently recognized by Marquis Who’s & Who Top Doctors for dedication, achievements, and leadership in neurology. Dr. Katz attended the Sackler School of Medicine at Tel Aviv University, where he earned an MD in 1976 with Magna Cum Laude. He went on to complete a residency in Internal Medicine at Sheba Medical Center in 1980, a residency in Neurology at Tel Aviv Medical Center in 1984, a fellowship in medical hypnosis at the University of Haifa in 1985, a fellowship in Clinical Neurophysiology at the Cleveland Clinic in 1988 and a fellowship in Clinical Epilepsy at the Yale School of Medicine in 1989. Dr. Katz additionally holds numerous certifications in his field, including an Israeli specialist’s Certificate in Neurology, which he earned in 1985 and American Board certification of Psychiatry and Neurology he earned in 1992. He was certified as a Diving Medical Officer in 1976 and a Medical Officer with the Israeli Academy of Military Medicine. He is in solo practice with MedAhead, Inc., in Orange, Connecticut since 2004. Dr. Katz has been the president of this company since 1995 and has also been a consulting neurologist and Assistant Clinical Professor of Neurology at Yale University School of Medicine from 1993 to 2013. He was a partner in Neurology Associates of Norwalk PC, from 1993 to 2002. During those years he served as the Medical Director of the Epilepsy Foundation of Connecticut. From 1993 to 2002, Dr. Katz was the Director of the Epilepsy Center, Co-Director of Diving Medicine and Associate Director of Sleep Medicine – all at Norwalk Hospital. From 1996 to 1998, he served as the medical director of Telemedicine Consultants America, LLC. In recognition of his accomplishments in his field, Dr. Katz has been the recipient of numerous awards and honors. He won the Merritt Putnam Fellowship of the American Foundation in Epilepsy in 1988, the William Gowers Epilepsy Fellowship of Abbott Pharmaceuticals in 1989 and the Hans Berger Epilepsy Fellowship of the American EEG Society in 1990. From 2002 to 2014, he was listed among the Top Doctors in the New York Metro Area with Castle Connolly, and in 2010 and 2013 he was named Most Compassionate Doctor by Patients’ Choice. In 2008, 2010, and 2012, he was awarded Best Doctor by Patients’ Choice, among myriad further accolades. In 2016 he opened a new Company, DK Electronics, LLC, to promote an FDA approved medical device he invented – FlowKeepers® – that helps prevent Deep Vein Thrombosis (DVT). In the past 5 years Dr, Katz ran an IRB approved clinical trial examining the safety and efficacy of intra thecal Immunoglobulin administration to patients with Alzheimer’s disease. A treatment that shows promise in a variety of neuroinflammatory conditions. In the coming years, he intends to experience continued growth and success with his medical device, his research and clinical trials.
Dr. Bruce Patterson
Treatment for Various Disease Entities
Feb 11, 2022 - 10:45 am - 11:30 am
Cytokine/Chemokine profiles have been described in a number of immune and autoimmune disorders. With the current SARS-CoV-2 pandemic, we have described specific immune signatures in both acute and in long COVID. Of widespread interest, many post-infectious chronic immune disorders share many of the same symptoms including fatigue, post-exertional malaise, and muscle/joint pain. We investigated the immune profiles in long COVID, post-vaccination long COVID, ME-CFS and Post-lyme. We found similarities in immune markers yet subtle differences in these conditions using machine learning and AI. Here, we present our immune signatures as well as possible mechanisms underlying the immune abnormalities. Further, we will present successful treatment regimens that target the specific immune abnormalities.
11:30 am- 12:15pm : Closing notes
Sleep disorders acquired as a result of autoimmune encephalopathy (AEID) secondary to infectious disease are quite significant and include insomnia (early, mid, late), non-restorative sleep, restless leg, paroxysmal nocturnal leg movements, sleep apnea (obstructive and central), nightmares, circadian rhythm shift and narcolepsy (with sleep attacks, cataplexy, sleep paralysis and hypnagogic hallucinations). Poor sleep quality is associated with impaired immunocompetence and contributes to disease progression. Identifying, categorizing and treating the sleep disorders associated with AEID is a critical component of treatment and improves immunocompetence.
Psychiatric manifestations acquired as a result of AEID are also quite significant. The causal association between Late Stage Lyme Disease and Post-Acute COVID-19 Sequelae has been well studied and are quite representative of the symptoms seen in chronic immune mediated psychiatric symptoms. Common symptoms include impaired attention span, brain fog, unfocused concentration, joint symptoms, depression, anxiety disorders, decreased frustration tolerance, working memory impairments, decreased functional capacity, short-term memory impairments, difficulty prioritizing multiple tasks, fatigue, non-restorative sleep, multitasking difficulties, sudden mood swings, hypersomnia, mental apathy, insomnia, tingling, word finding difficulties, name retrieval, headaches, sound hypersensitivity, paresis, anhedonia, depersonalization, cold intolerance, body temperature fluctuations, light sensitivity, sensory overload, and dysfluent speech. Treating these symptoms facilitates recovery.
It is estimated that about 10-20% of patients who contract Lyme disease will develop a chronic illness of autoimmune nature, some with symptoms consistent with AEIE. This can happen even if the infection is treated appropriately and in a timely manner. We named the neuropsychiatric condition that develops after Lyme disease - ANDAL (Autoimmune Neuropsychiatric Disorder Associated with Lyme disease).
Demonstrating antibodies targeting different cerebral antigens confirms the autoimmune nature of this condition and supports immuno-modulatory treatment approaches.
Discontinuing all anti-microbial agents and initiating weekly Intramuscular Benzathine Penicillin-G, 600,000 -1,200,000 Million units, can result in dramatic improvement within a few weeks of treatment in some patients. If there are prominent neuropathic symptoms or if there is no response to Benzathine Penicillin -G, immunoglobulins, intravenously or subcutaneously are prescribed. Other immune modulatory approaches as well as correcting cytokines imbalance will be discussed.
Cytokine/Chemokine profiles have been described in a number of immune and autoimmune disorders. With the current SARS-CoV-2 pandemic, we have described specific immune signatures in both acute and in long COVID. Of widespread interest, many post-infectious chronic immune disorders share many of the same symptoms including fatigue, post-exertional malaise, and muscle/joint pain. We investigated the immune profiles in long COVID, post-vaccination long COVID, ME-CFS and Post-lyme. We found similarities in immune markers yet subtle differences in these conditions using machine learning and AI. Here, we present our immune signatures as well as possible mechanisms underlying the immune abnormalities. Further, we will present successful treatment regimens that target the specific immune abnormalities.
Amiram Katz
MD, DABPN
Gary Kaplan
DO, DABFP, DABPM, FAAMA Medical Director at the Kaplan Center for Integrative Medicine . Clinical Associate Professor, Georgetown University School of Medicine
Joseph Bellanti
MD, Professor of Pediatrics and Microbiology-Immunology (Emeritus) Director, International Center for Interdisciplinary Studies of Immunology (ICISI) Georgetown University Medical Center
Brian Fallon
MD, MPH Professor of Clinical Psychiatry, Columbia University
Bruce Patterson
MD, CEO IncellDX
Calliope Dendrou
PhD, Dendrou Group Wellcome Centre of Human Genetics, Nuffield Department of Medicine, University of Oxford
Craig Shimasaki
PhD, MBA Co-founder & CEO Moleculera Labs, Inc.
Craig Shimasaki is co-founder and CEO of Moleculera labs, a neuroimmunology precision medicine company focused on identifying underlying roots of neurologic, psychiatric, and behavioral disorders triggered by an autoimmune response. The company’s research and clinical testing is focused on the molecular mimicry of common infections, and how they trigger autoimmune antibodies resulting in chronic and debilitating disorders of the brain, heart and immune system. The company’s blood testing panel is based on research from Dr. Madeleine Cunningham’s laboratory at the University of Oklahoma Health Sciences Center. Research has led to the identification of autoantibodies against targets associated with post-infectious neuropsychiatric sequalae such as dopamine D1, dopamine D2 receptors, autoantibodies directed against lysoganglioside GM1 and tubulin, as well as neuronal cell stimulatory activity of calcium-dependent calmodulin kinase II (CaMKII) simulating brain neurotransmitters.
Dr. Shimasaki received his BS in Biochemistry from University of California at Davis, his PhD in Molecular Biology from the University of Tulsa, and his MBA from Northwestern University, Kellogg School of Business. He an Adjunct Professor at the University of Oklahoma. His passion is to help translate scientific and medical discoveries into acutely needed products so that more patients can live healthier lives.
Dritan Agalliu
Associate Professor of Pathology and Cell Biology (Neurology). Columbia University Irving Medical Center
Research in Dr. Agalliu’s laboratory is focused on understanding the cellular and molecular mechanisms that regulate formation of the blood-brain barrier in the central nervous system ( CNS) and the mechanisms of neurovascular barrier breakdown in a variety of CNS diseases such as stroke and autoimmune diseases having symptoms that include blood-brain barrier failure, using a variety of genetic, molecular, cellular and imaging approaches. We have developed novel mouse strains that allow us to visualize changes in structural components of the blood-brain barrier, namely tight junctions and caveolae, in living animals for several CNS diseases (e.g. stroke and multiple sclerosis) in order to understand the cellular mechanisms underlying barrier impairment in these neurological disorders. In addition, we are investigating the role of Wnt/β-catenin signaling in development of the CNS vasculature and formation of the blood-brain barrier, and we are exploring the role of this pathway in repairing the barrier in diseases where its function is compromised (e.g. stroke and autoimmune disorders). Finally, we are investigating the mechanisms of immune cells entry into the CNS in a novel animal model for a neuropsychiatric disorder caused by multiple Streptococcus pyogenes infections, in order to understand how immune cells induce neurovascular, synaptic and behavioral deficits in the brain.
Hakima Amri
Professor, Physiology and Biochemistry Director, Integrative Medicine and Health Sciences Graduate Program Department of Biochemistry and Cellular & Molecular Biology Division of Integrative Physiology Georgetown University Medical Center
Harald Heidecke
PhD, CEO CellTrend GmbH
Javier Ochoa-Reparaz
Ph. D: Associate Professor at Eastern Washington University
Kim Lewis
Professor, Director Antimicrobial Discovery Center Northeastern University
Mark Opp
Professor, Department of Integrative Physiology, University of Colorado Boulder
Otávio Cabral Marques
MSc, PhD Associated Scientist , Laboratory of Integrative Immunology, Institute of Biomedical Sciences Universidade de Sāo Paulo
Otávio Cabral-Marques is an Associated Scientist at the Department of Immunology/Institute of Biomedical Sciences and the Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, both at the University of São Paulo. Biologist (2001-2005), He obtained his MSc (2006-2008) and PhD (2008-2012) degrees from the Institute of Biomedical Sciences - University of São Paulo (USP), performing his Sandwich PhD (Dec, 2010 - May, 2011) at the University of Washington/Seattle Children's Research Institute, USA. Otávio performed his Post-doctorate in Brazil (USP: 2012 - 2015) and Germany (University of Lubeck, Oct, 2015 - April, 2018; University of Freiburg: Apr, 2015 - Nov, 2019). Otavio is the Brazilian Junior Ambassador of the Universal Scientific Education and Research Network (USERN).
Robert Bransfield
MD, DLFAPA
Ru Rong Ji
PhD, PI Professor in Anesthesiology Distinguished Distinguished Professor of Anesthesiology, in the School of Medicine Professor in Neurobiology Professor in Cell Biology
Sarah Ramey
Writer and Musician
Susan Swedo
MD, NIH Science Emerita. Chief Science Officer of PANDAS Physicians Network
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