Central Nervous System Immunoglobulin Synthesis in Neurological Disease

Walsh, Michael J.; Tourtellotte, Wallace W.; Potvin, Alfred R.

doi:10.1007/978-1-4615-9269-3_19

Cited by 6 publications

(1 citation statement)

References 119 publications

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“…The presence of FLC has been widely interpreted as disclosing intense stimulation by Ag or by mitogen fractions within the CNS compartment. The resulting hyperstimulation of B cells and their differentiated products leads to a desynchronization of light and heavy chains assembly and the release of light chains fragments into the extracellular brain space from where they diffuse into the CSF [182]. These components are observed upon IF and subsequent immunofixation and immunostaining, as bands which are more anodic than oligoclonal IgG bands [ [157].…”

Section: The Significance Of Different Ig Isotypes and Igg Subclassesmentioning

confidence: 99%

Oligoclonal bands and antibody responses in Multiple Sclerosis

Correale

Molinas²

2002

J Neurol

108

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Multiple Sclerosis (MS) is an inflammatory disease of the Central Nervous System with multifocal areas of demyelination. Although its etiology and pathogenesis remain controversial, several lines of evidence indicate that MS is mediated by a misdirected immune response against one or several myelin proteins. The involvement of diverse leukocyte subsets and their products in MS is still the subject of considerable debate. The emphasis on T cells has derived mainly from the detection of activated T cells in MS plaques and analogies with animal models of MS. Because of these observations cell-mediated immunity has dominated the research field of MS to this day. However, in recent years the role of B cells, plasma cells and immunoglobulins in MS have been re-examined, and current findings indicate that humoral immunity also plays a major role in disease pathogenesis. B cells and their products could exert several potential effects during the course of MS. Firstly, autoantibodies against specific myelin antigens could mediate damage to myelin membranes. Secondly, some studies suggest that natural autoantibodies could enhance remyelination. Thirdly, antibodies directed against myelin components can participate in anti-idiotypic networks, which may regulate the course of MS. Increased intrathecal immunoglobulin synthesis reflected by raised IgG indices and an oligoclonal pattern is the most common abnormality detected in MS patients. The introduction of more sensitive procedures for protein detection has allowed demonstrating oligoclonal bands (OCBs) in up to 95 % of patients with clinically definite MS. Although the presence of OCBs in CSF of MS patients is now well established as a sensitive laboratory test to support the clinical diagnosis, OCBs may be present in other disorders, including those not directly related to infection or abnormal immune response. Nevertheless, the pathogenesis of OCBs in MS is still obscure, and despite extensive research their antigenic target(s) have yet to be established. Therefore, a critical task is to identify the specificity of such target(s), thus providing significant clues about MS etiology. For this purpose, novel molecular immunologic strategies have been recently developed to offer alternative approaches to identify putative antigens recognized by antibodies present in MS patients. The elucidation of the mechanisms and target(s) responsible for the onset of MS has obvious implications for the further development of specific therapies.

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Section: The Significance Of Different Ig Isotypes and Igg Subclassesmentioning

confidence: 99%

Oligoclonal bands and antibody responses in Multiple Sclerosis

Correale

Molinas²

2002

J Neurol

108

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Studies on B-Lymphocyte Function in Multiple Sclerosis

1984

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Deficit Schizophrenia Is Characterized by Defects in IgM-Mediated Responses to Tryptophan Catabolites (TRYCATs): a Paradigm Shift Towards Defects in Natural Self-Regulatory Immune Responses Coupled with Mucosa-Derived TRYCAT Pathway Activation

et al. 2017

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Deficit schizophrenia is accompanied by mucosa-associated activation of the tryptophan catabolite (TRYCAT) pathway, as indicated by increased IgA responses to noxious (NOX) TRYCATs, but not regulatory or protective (PRO) TRYCATs, suggesting increased neurotoxic, excitotoxic, inflammatory, and oxidative potential. No previous studies examined IgM-mediated autoimmune responses to the TRYCAT pathway in deficit versus nondeficit schizophrenia. We measured IgM responses to NOX TRYCATs, namely, quinolinic acid (QA), 3-OH-kynurenine (3HK), picolinic acid (PA), and xanthurenic (XA) acid, and PRO TRYCATs, including kynurenic acid (KA) and anthranilic acid (AA), in 40 healthy controls and 40 deficit and 40 nondeficit schizophrenic patients. We computed the IgM responses to NOX (QA + PA + 3HK + XA)/PRO (AA + KA) ratio and ∆ differences in IgA - IgM TRYCAT values and NOX/PRO ratio. Deficit schizophrenia is characterized by significantly attenuated IgM responses to all TRYCATs and NOX/PRO ratio and highly increased ∆IgA - IgM NOX/PRO ratio as compared to nondeficit schizophrenia and healthy controls. The negative symptoms of schizophrenia are significantly and positively associated with increased IgM responses directed against the KA/3HK ratio and ∆IgA - IgM NOX/PRO ratio. The findings support the view that deficit schizophrenia is a distinct subtype of schizophrenia that may be significantly discriminated from nondeficit schizophrenia. Deficit schizophrenia is accompanied by a highly specific defect in IgM isotype-mediated regulatory responses directed to the TRYCAT pathway. Lowered IgM regulatory responses together with mucosa-derived activation of the TRYCAT pathway may contribute to neuroprogression, negative symptoms, and deficit schizophrenia. All in all, a highly specific defect in the compensatory (anti-)inflammatory reflex system (CIRS), namely, natural IgM-mediated regulatory responses, may underpin deficit schizophrenia.

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Central Nervous System Immunoglobulin Synthesis in Neurological Disease

Cited by 6 publications

References 119 publications

Oligoclonal bands and antibody responses in Multiple Sclerosis

Oligoclonal bands and antibody responses in Multiple Sclerosis

Studies on B-Lymphocyte Function in Multiple Sclerosis

Deficit Schizophrenia Is Characterized by Defects in IgM-Mediated Responses to Tryptophan Catabolites (TRYCATs): a Paradigm Shift Towards Defects in Natural Self-Regulatory Immune Responses Coupled with Mucosa-Derived TRYCAT Pathway Activation

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