Clonal expansion of IgA-positive plasma cells and axon-reactive antibodies in MS lesions.
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.
Zhang
Yiping
Y
Department of Neurology, University of California, Irvine, 100 Irvine Hall, Irvine, CA 92697-4275, USA.
Da
Reng-Rong
RR
Hilgenberg
Lutz G
LG
Tourtellotte
Wallace W
WW
Sobel
Raymond A
RA
Smith
Martin A
MA
Olek
Michael
M
Nagra
Rashed
R
Sudhir
Gupta
G
van den Noort
Stanley
S
Qin
Yufen
Y
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
D000906:Antibodies; D007070:Immunoglobulin A; D007133:Immunoglobulin Joining Region; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D012333:RNA, Messenger