title: Analysis of immunoglobulin variable region genes of a human IgM anti-myeloperoxidase antibody derived from a patient with vasculitis.
abstract: 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.
authors.affiliation: Department of Medicine, Institute of Urology, Middlesex Hospital, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Longhurst
authors.forename: M R
authors.initials: MR
authors.lastname: Ehrenstein
authors.forename: B
authors.initials: B
authors.lastname: Leaker
authors.forename: F K
authors.initials: FK
authors.lastname: Stevenson
authors.forename: M
authors.initials: M
authors.lastname: Spellerberg
authors.forename: C
authors.initials: C
authors.lastname: Chapman
authors.forename: D
authors.initials: D
authors.lastname: Latchmen
authors.forename: D A
authors.initials: DA
authors.lastname: Isenberg
authors.forename: G
authors.initials: G
authors.lastname: Cambridge
mesh_terms: 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*
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D009195:Peroxidase