Intrathecal Immunoglobulin A Synthesis in Multiple Sclerosis: From Biological Aspects to Clinical Relevance

Intrathecal immunoglobulin A (IgA) synthesis in multiple sclerosis (MS) has long earned little attention, despite a potential significance in disease pathogenesis and prognosis. The presence of IgA-positive plasma cells in MS lesions and along damaged axons suggests a role in disease pathogenesis. A...

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Main Authors: Dariia Kliushnikova, Ferdinand Otto, Georg Pilz, Peter Wipfler, Andrea Harrer
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/1/108
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author Dariia Kliushnikova
Ferdinand Otto
Georg Pilz
Peter Wipfler
Andrea Harrer
author_facet Dariia Kliushnikova
Ferdinand Otto
Georg Pilz
Peter Wipfler
Andrea Harrer
author_sort Dariia Kliushnikova
collection DOAJ
description Intrathecal immunoglobulin A (IgA) synthesis in multiple sclerosis (MS) has long earned little attention, despite a potential significance in disease pathogenesis and prognosis. The presence of IgA-positive plasma cells in MS lesions and along damaged axons suggests a role in disease pathogenesis. Available clinical evidence about a potential positive or negative prognostic role is scarce and inconclusive. Recent observations, however, highlight the migration of immune regulatory IgA-producing plasma cells from the gut to the central nervous system (CNS) in experimental autoimmune encephalitis models. A connection between intrathecal IgA synthesis and the gut–brain axis in MS was further corroborated by the discovery of gut microbiota-specific IgA+ B cells in human CNS during relapse. In this review, we summarize current evidence on the occurrence and immunopathology of intrathecal IgA synthesis in MS, explore its biological implications, and address methodological challenges regarding the detection of IgA as a major limitation and possible source of inconsistencies in clinical studies. By synthesizing these diverse lines of evidence, we highlight the importance of further research and the need for standardized detection methods to clarify the role of IgA in MS pathogenesis, disease progression, and as potential biomarker.
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spelling doaj-art-7d9948ee02b442ae994831d534d8d9172025-01-24T13:25:13ZengMDPI AGBiomolecules2218-273X2025-01-0115110810.3390/biom15010108Intrathecal Immunoglobulin A Synthesis in Multiple Sclerosis: From Biological Aspects to Clinical RelevanceDariia Kliushnikova0Ferdinand Otto1Georg Pilz2Peter Wipfler3Andrea Harrer4Department of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, 5020 Salzburg, AustriaIntrathecal immunoglobulin A (IgA) synthesis in multiple sclerosis (MS) has long earned little attention, despite a potential significance in disease pathogenesis and prognosis. The presence of IgA-positive plasma cells in MS lesions and along damaged axons suggests a role in disease pathogenesis. Available clinical evidence about a potential positive or negative prognostic role is scarce and inconclusive. Recent observations, however, highlight the migration of immune regulatory IgA-producing plasma cells from the gut to the central nervous system (CNS) in experimental autoimmune encephalitis models. A connection between intrathecal IgA synthesis and the gut–brain axis in MS was further corroborated by the discovery of gut microbiota-specific IgA+ B cells in human CNS during relapse. In this review, we summarize current evidence on the occurrence and immunopathology of intrathecal IgA synthesis in MS, explore its biological implications, and address methodological challenges regarding the detection of IgA as a major limitation and possible source of inconsistencies in clinical studies. By synthesizing these diverse lines of evidence, we highlight the importance of further research and the need for standardized detection methods to clarify the role of IgA in MS pathogenesis, disease progression, and as potential biomarker.https://www.mdpi.com/2218-273X/15/1/108IgAmultiple sclerosiscerebrospinal fluidprognosisintrathecal immunoglobulin synthesis
spellingShingle Dariia Kliushnikova
Ferdinand Otto
Georg Pilz
Peter Wipfler
Andrea Harrer
Intrathecal Immunoglobulin A Synthesis in Multiple Sclerosis: From Biological Aspects to Clinical Relevance
Biomolecules
IgA
multiple sclerosis
cerebrospinal fluid
prognosis
intrathecal immunoglobulin synthesis
title Intrathecal Immunoglobulin A Synthesis in Multiple Sclerosis: From Biological Aspects to Clinical Relevance
title_full Intrathecal Immunoglobulin A Synthesis in Multiple Sclerosis: From Biological Aspects to Clinical Relevance
title_fullStr Intrathecal Immunoglobulin A Synthesis in Multiple Sclerosis: From Biological Aspects to Clinical Relevance
title_full_unstemmed Intrathecal Immunoglobulin A Synthesis in Multiple Sclerosis: From Biological Aspects to Clinical Relevance
title_short Intrathecal Immunoglobulin A Synthesis in Multiple Sclerosis: From Biological Aspects to Clinical Relevance
title_sort intrathecal immunoglobulin a synthesis in multiple sclerosis from biological aspects to clinical relevance
topic IgA
multiple sclerosis
cerebrospinal fluid
prognosis
intrathecal immunoglobulin synthesis
url https://www.mdpi.com/2218-273X/15/1/108
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AT georgpilz intrathecalimmunoglobulinasynthesisinmultiplesclerosisfrombiologicalaspectstoclinicalrelevance
AT peterwipfler intrathecalimmunoglobulinasynthesisinmultiplesclerosisfrombiologicalaspectstoclinicalrelevance
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