Clonal expansion of IgA-positive plasma cells and axon-reactive antibodies in MS lesions
| Autor: | Raymond A. Sobel, Yufen Qin, Stanley van den Noort, Martin A. Smith, Lutz G.W. Hilgenberg, Gupta Sudhir, Wallace W. Tourtellotte, Reng-Rong Da, Rashed M. Nagra, Yiping Zhang, Michael J. Olek |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Immunoglobulin A
Central Nervous System Male Pathology medicine.medical_specialty Silver Staining Multiple Sclerosis Immunology DNA Mutational Analysis Plasma Cells Antibodies Neurofilament Proteins Parenchyma medicine Immunology and Allergy Humans RNA Messenger Axon Perivascular space B-Lymphocytes biology Genes Immunoglobulin Reverse Transcriptase Polymerase Chain Reaction Multiple sclerosis Myelin Basic Protein Middle Aged medicine.disease Blotting Northern Immunohistochemistry Axons Myelin basic protein medicine.anatomical_structure Neurology Postmortem Changes biology.protein Immunoglobulin Joining Region Female Neurology (clinical) Antibody Infiltration (medical) |
| Zdroj: | Journal of neuroimmunology. 167(1-2) |
| ISSN: | 0165-5728 |
| Popis: | Immunoglobulin A (IgA), the predominant immunoglobulin class in mucosal secretions, has been found in the cerebrospinal fluid of patients with multiple sclerosis (MS). In this study we examined the infiltration of clonally expanded IgA plasma cells in lesions of MS brains. Sequences of complementarity-determining region 3 of IgA variable heavy chain (V(H)) genes demonstrated the clonal expansion of IgA-bearing plasma cells in MS lesions. Somatic mutations and ongoing intra-clonal mutations occurred in their V(H) genes. Immunohistochemical study demonstrated infiltration of dimer and polymer IgA1- and A2-positive plasma cells in perivascular spaces, in the parenchyma of MS lesions, and in the adjacent white matter. Double immunofluorescence staining showed binding of IgA antibody on axons and walls of microvessels in the areas of chronic active and inactive demyelination. Bielshowsky's silver impregnation revealed axonal damage in these areas. These findings suggest that IgA in the CNS are localized on axons in lesions and may contribute to axonal damage in MS. |
| Databáze: | OpenAIRE |
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