ANALYSIS OF IMMUNOGLOBULIN VARIABLE REGION GENES OF A HUMAN-IGM ANTIMYELOPEROXIDASE ANTIBODY DERIVED FROM A PATIENT WITH VASCULITIS

Circulating antibodies to myeloperoxidase (MPO) are associated primari ly with pauci-immune glomerulonephritis and systemic vasculitis. Anti- MPO antibodies belong to a group of autoantibodies, anti-neutrophil cy toplasmic antibodies, that may play a pathogenic role in vasculitis. W e have generated a human monoclonal anti-MPO antibody (E3-MPO) using p eripheral blood lymphocytes from a patient with microscopic polyarteri tis. Variable region gene analysis of E3-MPO showed that the VH region had 90% homology with the germ line gene V(H)4-21. E3-MPO was also sh own to carry the 9G4 idiotope, which so far has been associated only w ith 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 patie nt 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.