Immune system may mount an attack in Parkinson’s disease | National Institutes of Health (NIH)

Immune system may mount an attack in Parkinson’s disease | National Institutes of Health (NIH): "A research team led by David Sulzer, Ph.D., professor of neurology at Columbia University in New York City and Alessandro Sette, Dr.Biol.Sci., professor of infectious diseases at the La Jolla Institute for Allergy and Immunology in California, examined the role of T cells in PD.

Drs. Sulzer and Sette, along with their colleagues, collected blood samples from 67 individuals with Parkinson’s disease and 36 healthy controls. Immune cells were extracted from the samples and mixed with portions of the alpha-synuclein protein, which accumulates in the brains of people with PD and can result in cell death.

They found that T cells from people with PD responded to the presence of alpha-synuclein to a much greater degree than those gathered from the control group.

In particular, two regions of alpha-synuclein evoked reactions from T cells: a section that often contains mutations linked with PD, and a portion undergoing a chemical change that can lead to accumulation of the protein in the brain.  "

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Nature plus nurture: the triggering of multiple sclerosis.

Recent clinical and experimental studies indicate that multiple sclerosis develops as consequence of a failed interplay between genetic ("nature") and environmental ("nurture") factors. A large number of risk genes favour an autoimmune response against the body's own brain matter. New experimental data indicate that the actual trigger of this attack is however provided by an interaction of brain-specific immune cells with components of the regular commensal gut flora, the intestinal microbiota. This concept opens the way for new therapeutic approaches involving modulation of the microbiota by dietary or antibiotic regimens."

Role of stereotaxically injected IgG from db/db mice in the phosphorylation of the microtubule-associated protein tau in hippocampus.

People with type 2 diabetes (T2DM) mellitus are high risk for dementia and Alzheimer's disease (AD) via several plausible pathways. However, the underlying mechanisms have been still unclear, and the relation of immune injury to the pathogenesis of T2DM-related AD is not yet completely understood. Our present study aimed to elucidate the possible role of immunoglobulin IgG in the immune process of AD associated with T2DM in db/db mice. Hippocampi of 20 db/db mice and 20 C57BL/6 mice were subjected to immunohistochemistry and immunofluorescence assays. The phosphorylations of tau, glycogen synthase kinase (GSK)-3β and AKT activity was examined by Western blot analysis. IgG purified from the sera of IgG deposit-positive db/db mice was stereotaxically injected into the hippocampi of another 12 db/db mice and 12 C57BL/6 mice. The phosphorylation of tau, Abeta, GSK-3β and AKT activity was analysed. Compared with the C57BL/6 control, 13 of the 20 db/db mice exhibited high levels of IgG deposits in the hippocampus. Treatment with IgG triggered tau hyperphosphorylations and Abeta deposition, which are likely major factors in AD. Meanwhile, IgG inhibited AKT phosphorylation and promoted GSK-3β activity. The IgG deposits observed in some db/db mice were possibly related to the impairment of T2DM-related AD development. Some autoimmune processes may be involved in AD in type 2 diabetes mellitus development at the level of the hippocampus.

The robust electrochemical detection of a Parkinson's disease marker in whole blood sera - Chemical Science (RSC Publishing)

Protein aggregation, leading to amyloid deposition in the brain, is implicated in the pathology of a number of increasingly prevalent neurodegeneration states such as Parkinson's disease (PD), Alzheimer's disease and prion diseases. The body's protective response to the formation of such deposits is to generate specific autoimmune antibodies. Alpha-synuclein, a natively unfolded protein relatively abundant in the brain, is the main constituent of Lewy body amyloid dispositions in PD. Previous assays determining content of alpha-synuclein in bodily fluids have proven to be largely inconclusive. Here we have taken a novel approach in utilising alpha-synuclein modified electrodes to sample the autoantibodies generated as the body responds to changes in its homeostasis. We show that these electroanalytical assays not only robustly distinguish between disease state and control individuals but also map out disease progression with unprecedented sensitivity and clarity. The impedimetric electrode surfaces are highly specific, reusable, exhibit a linear range from 0.5 to 10 nM and a detection limit of 55 ± 3 pM. We believe electroanalyses such as these, possible with less than 10 microlitres of fluid and a total assay time of only a few minutes, to be of value for early diagnosis of PD and possibly other alpha-synucleinopathies, and for monitoring disease progression and effects of possible disease modifying interventions.

A vaccine for heart disease? New discovery points up this possibility

Researchers at the La Jolla Institute for Allergy & Immunology have identified the specific type of immune cells (CD4 T cells) that orchestrate the inflammatory attack on the artery wall. Further, the researchers discovered that these immune cells behave as if they have previously seen the antigen that causes them to launch the attack. "The thing that excites me most about this finding is that these immune cells appear to have 'memory' of the molecule brought forth by the antigen-presenting cells," said Klaus Ley, M.D., a renowned expert in vascular immunology, who led the study in mouse models. "Immune memory is the underlying basis of successful vaccines. This means that conceptually it becomes possible to consider the development of a vaccine for heart disease."

Do Bugs Control Our Fate? The Influence of the Microbiome on Autoimmunity.

Autoimmune disease has traditionally been thought to be due to the impact of environmental factors on genetically susceptible individuals causing immune dysregulation and loss of tolerance. However, recent literature has highlighted the importance of the microbiome, (a collective genome of microorganisms in a given niche) in immune homeostasis. Increasingly, it has been recognized that disruptions in the commensal microflora may lead to immune dysfunction and autoimmunity. This review summarizes recent studies investigating the interplay between the microbiome and immune-mediated organ-specific diseases. In particular, we review new findings on the role of the microbiome in inflammatory bowel disease, celiac disease, psoriasis, rheumatoid arthritis, type I diabetes, and multiple sclerosis.

NIH researchers implicate unique cell type in multiple sclerosis, August 1, 2012 News Release - National Institutes of Health (NIH)

Researchers at the National Institutes of Health have found evidence that a unique type of immune cell contributes to multiple sclerosis (MS). Their discovery helps define the effects of one of the newest drugs under investigation for treating MS — daclizumab — and could lead to a new class of drugs for treating MS and other autoimmune disorders.
In these disorders, the immune system turns against the body's own tissues. Ongoing clinical trials have shown that daclizumab appears to help quiet the autoimmune response in MS patients, but its precise effects on the legions of cells that make up the immune system are not fully understood.
The new study, published in Science Translational Medicine, shows that one effect of daclizumab is to thin the ranks of lymphoid tissue inducer (LTi) cells. These cells are known to promote the development of lymph nodes and related tissues during fetal life, but their role during adulthood has been unclear. The new study marks the first time that LTi cells have been implicated in any human autoimmune disorder.

Research team uncovers mechanism behind drugs that cause altered immunity

(Medical Xpress) -- An Australian research team has opened the door to understanding why certain drugs cause a so called altered immunity response when offered as treatment for certain specific ailments. In their paper published in the journal Nature, the team explains how they’ve uncovered the mechanism that causes an HIV treatment drug to lead to hypersensitivity syndrome.

Possible role of autoantibodies in Alzheimer’s

New research by scientists at the University of Medicine and Dentistry of New Jersey-School of Osteopathic Medicine (UMDNJ-SOM) demonstrates how dying or damaged brain cells release debris into the bloodstream and give rise to specific autoantibodies that appear to be reliable biomarkers for early diagnosis of Alzheimer's and other neurodegenerative diseases. The researchers also identify a key mechanism in the development of Alzheimer's that mirrors a process that is common in such autoimmune disorders as rheumatoid arthritis.

Scientists discover special class of natural fats stimulates immune cells to fight diseases

An international research team led by scientists from Singapore Immunology Network (SIgN) under the Agency of Science, Technology and Research (A*STAR) discovered that a special class of fatty molecules is essential for activating a unique group of early-responding immune cells. This study sheds light on how recognition of fatty molecules by immune cells could protect from infection, allergic reactions, autoimmune diseases and cancer. More importantly, it offers new opportunities to exploit the use of these stimulatory fatty molecules in therapeutic interventions, such as the development of new vaccines and drugs targetted for autoimmune diseases.

Study shows how the breakup of two proteins interferes with the immune system

Autoimmune diseases, such as Type I diabetes and rheumatoid arthritis, are caused by an immune system gone haywire, where the body's defense system assaults and destroys healthy tissues. A mutant form of a protein called LYP has been implicated in multiple autoimmune diseases, but the precise molecular pathway involved has been unknown. Now, in a paper published March 18 in Nature Chemical Biology, researchers at Sanford-Burnham Medical Research Institute show how the errant form of LYP can disrupt the immune system. In doing so, they also found a potential new therapy for autoimmune diseases—a chemical compound that appears to inhibit this mutant protein.

Autoimmune diseases the target of new research

PhD student Rhianna Lindop has developed a world-first technique in conjunction with Flinders proteomics experts Dr. Georgia Arentz and Dr. Tim Chataway to analyse a type of antibody that contributes to the disease progression of lupus and Sjogren’s syndrome, resulting in vital new information that could ultimately lead to targeted therapies.

Schizophrenia in patients with atopic disorders with particular emphasis on asthma: A Danish population-based study.

Autoimmune diseases and infections have been associated with an increased risk of schizophrenia that could be rooted in inflammatory mechanisms. However, other diseases characterized by a heightened immune response, such as atopic disorders, remain to be thoroughly investigated. The aim of this study was to investigate whether atopic disorders in the individual or in a first-degree relative affect the risk of developing schizophrenia. 

METHOD:

We linked two nationwide population-based registers: the Danish Psychiatric Central Register and the National Hospital Register. Two longitudinal designs were used: a cohort study and a case/sibling study. Rate ratios (RRs) and accompanying 95% confidence intervals (CIs) were obtained. 

RESULTS:

Hospital contact with any atopic disorder increased the RR of schizophrenia by 1.45 (95% CI=1.31-1.90). The increased risk was mainly driven by asthma: 1.59 (95% CI=1.31-1.90); this was confirmed when cases were compared with siblings instead of the background population. Hospital contact with other included atopic disorders (atopic dermatitis, urticaria and allergic rhinitis) increased the risk of schizophrenia significantly only if they were combined into one group. Hospital contact with asthma in a first-degree relative did not significantly increase the risk of schizophrenia. 

CONCLUSION:

This study indicates the existence of an association between atopic disorders in general and asthma in particular and the risk of developing schizophrenia. The study adds to a growing body of literature suggesting the possible involvement of immune processes in the pathophysiology of schizophrenia.Copyright © 2012 Elsevier B.V. All rights reserved.

Researcher steps closer to understand autoimmune diseases

Understanding why immune cells, called T-cells, attack the body is vital in the war against autoimmune diseases like diabetes. University of Alberta researcher Troy Baldwin is a step closer to understanding why the body's T-cells sometimes attack healthy cells causing autoimmune diseases.

Glutamic Acid decarboxylase autoantibody syndrome presenting as schizophrenia.

INTRODUCTION:

: Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme converting glutamate into γ-aminobutyric acid. Impaired GAD function can alter motor, cognitive, and behavioral function. Anti-GAD antibodies (GADAbs) can cause several neurological disorders. However, the association between anti-GADAbs and pure psychosis, without seizures or focal neurological deficits, is not well defined.

CASE REPORT:

: A 19-year-old woman with recent-onset psychotic disorder was diagnosed with schizophrenia. Brain magnetic resonance imaging and cerebrospinal fluid analysis were normal. Serum anti-GADAb titers were elevated. Brain biopsy showed subcortical gliosis and microglia-macrophage infiltration. The clinical syndrome improved with immune therapy.

CONCLUSIONS:

: Severe psychosis and mild cognitive decline without other neurological features, meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision diagnostic criteria for schizophrenia, can result from brain inflammation associated with elevated serum anti-GADAbs.

Sensing self and non-self: New research into immune tolerance

At the most basic level, the immune system must distinguish self from non-self, that is, it must discriminate between the molecular signatures of invading pathogens (non-self antigens) and cellular constituents that usually pose no risk to health (self-antigens).

Why Bad Immunity Genes Survive - US National Science Foundation (NSF)

Biologists have found new evidence of why mice, people and other vertebrate animals carry thousands of varieties of genes to make immune-system proteins named MHCs--even though some of those genes make vertebrate animals susceptible to infections and to autoimmune diseases.

Microbiota in autoimmunity and tolerance.

The composition of a host's intestinal microbiota directs the type of mucosal and systemic immune responses by affecting the proportion and number of functionally distinct T cell subsets. In particular, the microbiota composition affects the differentiation of intestinal Th17 cells and Foxp3(+) regulatory T cells, both of which play critical roles in maintaining mucosal barrier functions and in controlling immunological homeostasis. In this review, we discuss the recent advances in our understanding of how the intestinal microbiota affects T cell differentiation and host susceptibility to autoimmune disease.

Antiviral CD8(+) T cells cause an experimental autoimmune encephalomyelitis-like disease in naive mice.

Major histocompatibility complex class I-restricted CD8(+) cytotoxic T lymphocytes are involved in the pathogenesis of multiple sclerosis (MS) and both autoimmune, experimental autoimmune encephalomyelitis, and viral, Theiler's murine encephalomyelitis virus (TMEV) infection, animal models of MS. Following TMEV infection, certain T cell hybridomas, generated from cloned TMEV-induced CD8(+) T cells, were able to produce clinical signs of disease (flaccid hind limb paralysis) upon adoptive transfer into naive mice. Dual T cell receptors (TCR) are present on the surface of these cells as both Vβ3 and Vβ6 were detected by polymerase chain reaction (PCR) screening and flow cytometry and multiple Vα mRNAs were detected by PCR screening. This is the first demonstration of antiviral CD8(+) T cells having more than one TCR initiating an autoimmune disease in the natural host of the virus. We hypothesize that this is a potential mechanism for virus-induced autoimmune disease initiated by CD8(+) T cells.

Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination.

Commensal gut flora-in the absence of pathogenic agents-is essential in triggering immune processes, leading to a relapsing-remitting autoimmune disease driven by myelin-specific CD4(+) T cells.

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• Mutation drives viral sensors to initiate autoimmune disease (polygenicpathways.blogspot.com)