Analysis of immunoglobulin variable region genes of a human IgM anti-myeloperoxidase antibody derived from a patient with vasculitis.
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 VH region had 90% homology with the germ line gene VH4-21. E3-MPO was also shown to carry the 9G4 idiotope, which so far has been associated only with human antibodies that utilize the VH4-21 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.
Longhurst
C
C
Department of Medicine, Institute of Urology, Middlesex Hospital, London, UK.
Ehrenstein
M R
MR
Leaker
B
B
Stevenson
F K
FK
Spellerberg
M
M
Chapman
C
C
Latchmen
D
D
Isenberg
D A
DA
Cambridge
G
G
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics*; D001323:Autoantibodies / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000032:analysis; D007075:Immunoglobulin M / Q000737:chemistry / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009195:Peroxidase / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D009195:Peroxidase