Immune System Diseases Commons^™

Objectivity, Practicality, And Significance Of Practice Guidelines For The Practicing Neurologists: What We Learnt From Consensus Criteria In Cidp, Myasthenia Gravis And Inflammatory Myopathies, Marinos C. Dalakas

Department of Neurology Faculty Papers

The value of practice guidelines in the three most common autoimmune neuromuscular disorders, namely Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Myasthenia Gravis (MG) and Autoimmune Inflammatory Myopathies (AIM), has been extensively debated regarding their usefulness in clinical practice, objectivity and universal value considering that guidelines are also established regionally in certain countries. This commentary highlights common concerns on how guidelines are presently generated, pointing out: (a) non-sufficient diversity among Task-Force members to identify and address not only routine clinical and electrophysiology issues but also immunology, imaging, pathology, biomarkers, epidemiology or treatment economics; (b) Task-Force being often comprised by the same or …

Case Report: Abrupt Psychosis Or Nmda Receptor Encephalitis?, Alexis Dunn, Neelesh Parikh, James Espinosa, Alan Lucerna

Rowan-Virtua Research Day

We report a case of a 46-year-old female who was initially committed to a psychiatric facility for new onset schizophrenia symptoms. She later had an extensive workup in the hospital due to leukocytosis and was believed to have NMDA Receptor Encephalitis as the cause for her new behavioral symptoms. This case report aims to educate EM (emergency medicine) physicians to keep a broad differential diagnosis on patients who present with new onset, unprovoked psychosis later in life.

Infiltrating Cd8+ T Cells Exacerbate Alzheimer’S Disease Pathology In A 3d Human Neuroimmune Axis Model, Jefin Jose, Devam Purohit

VCU's Medical Journal Club: The Work of Future Health Professionals

In this study, Jorfi et al. employed a neuroimmune axis model containing neurons, astrocytes, and microglia to examine the role of immune cells in Alzheimer's disease. Jorfi et al. found that T cells selectively infiltrated the BRAIN compartment of the neuroimmune axis model as compared to B cells and monocytes. Jorfi et al. further found that CD8+ T cells demonstrated heightened cytotoxicity in the Alzheimer's disease brain, illuminating the role of immune cells in neurodegeneration. Upon further examination, the CXCR3-CXCL10 signaling pathway was found to have an important role in inflammation.

A Genome-Wide In Vivo Crispr Screen Identifies Essential Regulators Of T Cell Migration To The Cns In A Multiple Sclerosis Model, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

Kendirli et al. (2023) used a CRISPR screen to determine the proteins involved in T cell migration into the CNS in multiple sclerosis. Overall, eighteen facilitators and five brakes to T cell infiltration into the CNS were identified. Kendirli et al. specifically identified ITGA4, FERMT3, and HSP90B1 to make up the adhesion module, CXCR3, GNAI2, and TBX21 to make up the chemotaxis module, and GRK2 and S1PR2 to make up the egress module. This study demonstrated the ability of a CRISPR screen to identify elements in a disease process and thus identify targets for future multiple sclerosis therapies.

Guillain-Barré Syndrome: Recognizing Variations In Clinical Presentations, Andrew Wang, Komal Luthra

Gulf Coast Division GME Research Day 2023

No abstract provided.

Multiple Sclerosis In A 32-Year-Old Female With History Of Prolactinoma, Aleeza Ali, Jesse Simon, Adekunle Bamgboye

East Florida Division GME Research Day 2023

Among disorders affecting the central nervous system (CNS), excluding trauma, multiple sclerosis (MS) is the most common cause of permanent disability in young adults. This condition is characterized by IgG autoantibody-mediated destruction of oligodendrocytes in the brain and spinal cord. Although the origin of MS is not fully understood, some suggest that prolactin may be involved in the development of the disease process evidenced by the fact that it predominately affects women of childbearing age, and the diverse role of prolactin (PRL) as a peptide hormone, cytokine, and immune modulator. Here we review the case of a 32-year-old female with …

Bulbar-Predominant Presentation Of Myasthenia Gravis: Poster Presentation, Duncan Mckinney, Rumana Khan, Edward Griffin

Capital Division GME Research Day 2023

No abstract provided.

Neurolupus In A Previously Healthy Young Caucasian Male, Kavanya Feustel, Joshua Ralston, Kelly Schulte, Jeffrey Ramsey, Deren Goker, Jacob Keeling, Dmitriy Scherbak

Continental, MidAmerica, & Mountain Divisions GME Research Day 2023

No abstract provided.

Glial Cell-Specific Contribution Of Pkr-Like Er Kinase (Perk) In Neuroinflammation And Behavior, Anirudhya Lahiri

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neurological disorders such as multiple sclerosis (MS) are a major public health concern in the US, with no available therapeutic cure. Chronic neuroinflammation and aberrant proteostasis in the central nervous system (CNS) are the major hallmarks of neurological diseases. Endoplasmic Reticulum (ER) is a major cellular organelle involved in protein synthesis, folding and maturation of various secretory and transmembrane proteins. Pathophysiological stressors such as trauma and infection result in misfolded protein accumulation in the endoplasmic reticulum (ER) lumen, which results in ER stress. To regain proteostasis (protein homeostasis), cells activate the unfolded protein response (UPR). UPR is an evolutionarily conserved …

Myasthenia Gravis, Rebecca Wheeler

Nursing Student Class Projects (Formerly MSN)

Myasthenia gravis (MG), a neuromuscular and autoimmune disorder, is not completely understood by clinicians and scientists. The primary cause is thought to be anti-Acetylcholine receptor antibodies that attack the neuromuscular junction, causing destruction of post-synaptic junctional folds and blockade of the receptor. This causes frequent weakness and fatigability of voluntary muscles, making activities of daily living difficult for those living with MG. Although it is not an incredibly prevalent disease, the incidence is increasing in the United States due to better testing and diagnosis. Treatments are available, including cholinesterase inhibitors that raise the concentration of Acetylcholine at the neuromuscular junction …

Identification Of Therapeutic Targets For Th17 Cell-Mediated Diseases, Jin Wang

Theses and Dissertations (ETD)

Hypersensitivity and autoimmune diseases are complex synergistic effect of environmental, genetic and other factors. T helper 17 (Th17) cells play a critical role in the immune pathology. Th17 cells are a group of specialized CD4+ T cells with potential pro-inflammatory function which are different from other T cells such as T helper 1 (Th1) cells or T helper 2 (Th2) cells. Th17 cell development and differentiation processes are strictly regulated through complex pathways. Th17 cells are characterized by secreting cytokines such as IL-17 and IL-22. Studies have shown that Th17 cells and IL-17 have been implicated in the pathogenesis of …

Ameliorative Effects Of Minor Cannabinoids Over Hiv-1 Tat-Mediated Visceral Pain, Charlie Worth

Honors Theses

As the total number of people living with HIV continues to rise across the world, an effective HIV treatment is still sought after. While modern-day advanced therapies exist for mitigating much of the negative effects of HIV, the virus remains evasive and problematic in the central nervous system. Thus, even with treatment, many people living with HIV continue to suffer from a plethora of symptoms. However, a large proportion of HIV-positive patients claim to feel a reduction in those persevering symptoms after cannabis usage. This anecdotal evidence has sparked interest in the efficacy of cannabis constituents for HIV therapy. This …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Plethora Of Cranial Nerve Palsies: A Problematic Presentation Of Myasthenia Gravis, Nichole Birdsong, Sean Gibbs, Jerry Banks

South Atlantic Division GME Research Day 2022

No abstract provided.

Multiple Sclerosis And Its Symptom Management Through Supplementation And Dietary Planning, Lindsey J. Davis

Selected Honors Theses

Multiple Sclerosis (MS) is an autoimmune, neuroinflammatory disorder that is characterized by the breakdown of myelinated axons in the Central and Peripheral Nervous Systems. It is a potentially debilitating autoimmune disease that affects almost 1 million people in the United States, and nearly 2.5 million people worldwide. The precise etiology of MS is still being researched, but much progress has been made towards understanding the molecular mechanisms and impactful ways to treat this disease. While there is still no cure, new treatment plans are constantly being orchestrated in effort to alleviate the burden that MS carries. Combination treatment plans have …

Plasma Proteins That May Cause Parkinson’S Disease And Multiple Sclerosis: A Mendelian Randomization Study, Brigid A. Staley

Dissertations and Theses

Multiple sclerosis (MS) and Parkinson’s disease (PD) are progressively disabling neurologic disorders that profoundly affect quality of life and shorten life expectancy. There is no cure for either disease, and current treatments only alleviate symptoms and may cause serious side effects. The causes of MS and PD are not well understood. Previous epidemiologic studies have documented numerous environmental risk factors for both diseases. However, these studies are inherently prone to bias from confounding which may generate spurious results. The lack of unbiased evidence on environmental causes of MS and PD has been a critical barrier to fully understanding their pathophysiology. …

Organic Compound Farnesol Reduces Disease Severity And Onset In Mouse Model Of Multiple Sclerosis, Lacey B. Sell

EWU Masters Thesis Collection

No abstract provided.

Guillain Barre Syndrome In A Patient With Sickle Cell Anemia, Kunjan Udani Md, Pooja Patel, Dveet Patel, Hajra Awwab, Nino Balanchivadze

Internal Medicine

No abstract provided.

Ticked Off: How Expansion Of City Boundaries Affects Rates Of Lyme Disease In The United States, Daphne Fauber

The Journal of Purdue Undergraduate Research

No abstract provided.

An Integrative Approach To Mindfulness-Based Symptom Management For Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Lisa Barer

Mindfulness Studies Theses

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic health condition; its etiology is poorly understood, and treatment options are limited to management of symptoms. Current recommended treatment options are controversial, and evidence of effectiveness is limited. This paper proposes a novel model for symptom management of ME/CFS using mindfulness-based interventions, cognitive behavioural therapy (CBT), and relaxation techniques. A comprehensive review of available evidence is used to support this approach. The idea is that, working synergistically, these three approaches, grounded by mindfulness-based principles, can address many of the symptoms of the illness and help patients better cope and manage their day-to-day …

Male Determining Gene Nix May Bring An End To Transmission Of Diseases Through Mosquitoes, Mohammed Mahdi

Thinking Matters Symposium Archive

Female mosquitoes take blood from humans to gain protein needed to produce eggs, and in the process they can transmit viruses, such as Zika, Dengue, and chikungunya, or parasites, such as malaria. Male mosquitoes do not transmit diseases. This literature review will examine what is known about how sex is determined in mosquitoes and how this can be used to manipulate the females that spread diseases to humans. Using CRISPR Cas9, the lab of Zhijian Tu removed the Nix gene from mosquito embryos; all of these were feminized. Ectopic overexpression of Nix gene product in mosquito embryos caused even genetically …

Assistive Utensil: A Spork For Hand Tremors And Spatial Awareness, Ana Font Hernandez, Jacob Kabariti, Troy Taylor

Publications and Research

In this poster, we present a 3D printed solution for hand tremors and special awareness. Our spork is an assistive device designed and 3D printed for patients suffering from scleroderma, systemic sclerosis, Parkinson's, multiple sclerosis, drug withdrawal, etc. The scale-based handle will act as a counterweight to offset the contents on the other end and reduce shakiness. The larger grip allows an easy and comfortable hold. The product will be 3D printed for a customizable fit and at an affordable price. Lastly, the product will include a haptic feedback sensor to assist the visually impaired in locating food contents on …

Antibodies To Heterogenous Nuclear Ribonucleoprotein A1 Penetrate Neurons Leading To Multiple Downstream Effects Resulting In Neurodegeneration, Joshua Nathan Douglas

Theses and Dissertations (ETD)

Multiple sclerosis (MS) is the most common demyelinating disorder of the central nervous system. MS is believed to occur in genetically susceptible individuals due to an unknown environmental stimulus. MS patients produce autoantibodies to heterogenous nuclear ribonuclearprotein A1 (hnRNP A1), an RNA binding protein (RBP) highly expressed in neurons. hnRNP A1 functions in pre-mRNA splicing, mRNA trafficking, and translation. Furthermore, the anti-hnRNP A1 antibodies are specific to a N-terminal region termed ‘M9’ which serves as a nuclear export sequence/nuclear localization sequence (NES/NLS) responsible for nuclear/cytoplasmic transport of the protein. In this manuscript we will provide data revealing that anti-hnRNP A1 …

Cyclophosphamide For Suspected Primary Angiitis Of The Central Nervous System In A Patient With Human Immunodeficiency Virus: A Case Report, Martha M. Rumore, Samantha Su, Jake Pellinen

Touro College of Pharmacy (New York) Publications and Research

Introduction: Central nervous system (CNS) vasculitis is rare, including in human immunodeficiency virus (HIV), occurring in less than 1% of patients. Systemic vasculitis affecting the CNS is termed secondary CNS vasculitis, whereas primary CNS vasculitis, referred to as primary angiitis of the CNS (PACNS) refers to an extremely rare disease specifically confined to the CNS. Only some cases of PACNS in HIV patients have been reported in literature.

Case Report: We report a case of a 46-year-old female with HIV who developed probable primary CNS vasculitis, which was treated with intravenous cyclophosphamide and glucocorticoids for both induction and …

Utility And Origin Of Blood-Based Autoantibodies For Early Detection And Diagnosis Of Neurodegenerative Diseases, Cassandra Demarshall

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies are self-reactive antibodies that have been widely implicated as causal agents of autoimmune diseases. They are found in the blood of all human sera, regardless of age, gender, or the presence or absence of disease. While the underlying reason for their ubiquity remains unknown, it has been hypothesized that they participate in the clearance of blood-borne cell and tissue debris generated in both healthy and diseased individuals on a daily basis. Although much evidence supports this debris clearance role, recent studies also suggest a causal role for autoantibodies in disease. My thesis work has focused on this "cause and/or …

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …

An Epitope From Acanthamoeba Castellanii That Cross-React With Proteolipid Protein 139-151-Reactive T Cells Induces Autoimmune Encephalomyelitis In Sjl Mice, Chandirasegaran Massilamany, David Steffan, Jay Reddy

Jay Reddy Publications

We report here that an epitope (aa, 83-95) derived from Acanthamoeba castellanii (ACA) induces clinical signs of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice reminiscent of the disease induced with myelin proteolipid protein (PLP) 139-151. By using IA^s/tetramers, we demonstrate that both ACA 83-95 and PLP 139-151 generate antigen-specific cross-reactive CD4 T cells and the T cells secrete identical patterns of cytokines and induce EAE with a similar severity. These results may provide insights into the pathogenesis of multiple sclerosis and ACA-induced granulomatous encephalitis.

Distinct Functions Of Autoreactive Memory And Effector Cd4+ T Cells In Experimental Autoimmune Encephalomyelitis, Wassim Elyaman, Pia Kivisäkk, Jay Reddy, Tanuja Chitnis, Khadir Raddassi, Jaime Imitola, Elizabeth Bradshaw, Vijay K. Kuchroo, Hideo Yagita, Mohamed H. Sayegh, Samia J. Khoury

Jay Reddy Publications

The persistence of human autoimmune diseases is thought to be mediated predominantly by memory T cells. We investigated the phenotype and migration of memory versus effector T cells in vivo in experimental autoimmune encephalomyelitis (EAE). We found that memory CD4⁺ T cells up-regulated the activation marker CD44 as well as CXCR3 and ICOS, proliferated more and produced more interferon-γ and less interleukin-17 compared to effector T cells. Moreover, adoptive transfer of memory T cells into T cell receptor (TCR)αβ^-/- recipients induced more severe disease than did effector CD4⁺ T cells with marked central nervous system inflammation and …

Peptide 15-Mers Of Defined Sequence That Substitute For Random Amino Acid Copolymers In Amelioration Of Experimental Autoimmune Encephalomyelitis, Joel N.H. Stern, Zsolt Illés, Jay Reddy, Derin B. Keskin, Masha Fridkis-Hareli, Vijay K. Kuchroo, Jack L. Strominger

Jay Reddy Publications

Myelin basic protein (MBP) is a major candidate autoantigen in multiple sclerosis (MS). Its immunodominant epitope, MBP 85–99, forms a complex with human leukocyte antigen (HLA)-DR2 with which multiple sclerosis is genetically associated. Copolymer 1 (Copaxone), a random amino acid copolymer [poly (Y,E,A,K)n] as well as two modified synthetic copolymers [poly (F,Y,A,K)n and poly (V,W,A,K)n] also form complexes with HLA-DR2 (DRA DRB1*1501) and compete with MBP 85–99 for binding. Moreover, two high-affinity synthetic peptide 15-mers that could inhibit binding even more effectively were previously designed. Here, we show that further-modified peptide 15-mers inhibited even more strongly (in order J5 > J3 …

Modified Amino Acid Copolymers Suppress Myelin Basic Protein 85–99-Induced Encephalomyelitis In Humanized Mice Through Different Effects On T Cells, Zsolt Illés, Joel N.H. Stern, Jay Reddy, Hanspeter Waldner, Marcin P. Mycko, Celia F. Brosnan, Stephan Ellmerich, Daniel M. Altmann, Laura Santambrogio, Jack L. Strominger, Vijay K. Kuchroo

Jay Reddy Publications

A humanized mouse bearing the HLA-DR2 (DRA/DRB1*1501) pro- tein associated with multiple sclerosis (MS) and the myelin basic protein (MBP) 85–99-specific HLA-DR2-restricted T cell receptor from an MS patient has been used to examine the effectiveness of modified amino acid copolymers poly(F,Y,A,K)n and poly- (V,W,A,K)n in therapy of MBP 85–99-induced experimental auto-immune encephalomyelitis (EAE) in comparison to Copolymer 1 [Copaxone, poly(Y,E,A,K)n]. The copolymers were designed to optimize binding to HLA-DR2. Vaccination, prevention, and treatment of MBP-induced EAE in the humanized mice with copolymers FYAK and VWAK ameliorated EAE more effectively than Copolymer 1, reduced the number of pathological lesions, and …