title: Clonal expansion of IgA-positive plasma cells and axon-reactive antibodies in MS lesions.
abstract: 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.
authors.affiliation: Department of Neurology, University of California, Irvine, 100 Irvine Hall, Irvine, CA 92697-4275, USA.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Zhang
authors.forename: Reng-Rong
authors.initials: RR
authors.lastname: Da
authors.forename: Lutz G
authors.initials: LG
authors.lastname: Hilgenberg
authors.forename: Wallace W
authors.initials: WW
authors.lastname: Tourtellotte
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Sobel
authors.forename: Martin A
authors.initials: MA
authors.lastname: Smith
authors.forename: Michael
authors.initials: M
authors.lastname: Olek
authors.forename: Rashed
authors.initials: R
authors.lastname: Nagra
authors.forename: Gupta
authors.initials: G
authors.lastname: Sudhir
authors.forename: Stanley
authors.initials: S
authors.lastname: van den Noort
authors.forename: Yufen
authors.initials: Y
authors.lastname: Qin
mesh_terms: D000906:Antibodies / Q000494:pharmacology*; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D001402:B-Lymphocytes / Q000378:metabolism; D015152:Blotting, Northern / Q000379:methods; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005803:Genes, Immunoglobulin / Q000502:physiology; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics / Q000378:metabolism*; D007133:Immunoglobulin Joining Region / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D004676:Myelin Basic Protein / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D010950:Plasma Cells / Q000276:immunology*; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016622:Silver Staining / Q000379:methods
chemical_list: D000906:Antibodies; D007070:Immunoglobulin A; D007133:Immunoglobulin Joining Region; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D012333:RNA, Messenger