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Analysis of immunoglobulin variable region genes of a human IgM anti‐myeloperoxidase antibody derived from a patient with vasculitis
Author(s) -
LONGHURST C.,
EHRENSTEIN M. R.,
LEAKER B.,
STEVENSON F. K.,
SPELLERBERG M.,
CHAPMAN C.,
LATCHMEN D.,
ISENBERG D. A.,
CAMBRIDGE G.
Publication year - 1996
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1996.463529.x
Subject(s) - myeloperoxidase , antibody , vasculitis , autoantibody , proteinase 3 , immunology , idiotopes , systemic vasculitis , monoclonal antibody , idiotype , biology , microbiology and biotechnology , medicine , pathology , inflammation , disease
Circulating antibodies to myeloperoxidase (MPO) are associated primarily with pauci‐immune glomerulonephritis and systemic vasculitis. Anti‐MPO antibodies belong to a group of autoantibodies, anti‐neutrophil cytoplasmic antibodies, that may play a pathogenic role in vasculitis. We have generated a human monoclonal anti‐MPO antibody (E3‐MPO) using peripheral blood lymphocytes from a patient with microscopic polyarteritis. Variable region gene analysis of E3‐MPO showed that the V H region had 90% homology with the germ line gene V H 4‐21. E3‐MPO was also shown to carry the 9G4 idiotope, which so far has been associated only with human antibodies that utilize the V H 4‐21 gene. The 9G4 idiotope was also expressed on anti‐MPO antibodies in sera from the donor patient and from 4/7 additional patients with active, untreated vasculitis. The nucleotide sequences of both the variable heavy and light chains of E3‐MPO showed evidence of an antigen‐driven response.