title: Production of human monoclonal antibodies to myeloperoxidase.
abstract: Two mouse-human heterohybridomas secreting human antibodies to myeloperoxidase (MPO) were derived from the peripheral blood of a patient who developed microscopic polyarteritis as the result of long-term treatment with hydralazine. Forty-five immunoglobulin-secreting lines were obtained from the fusion of patient lymphocytes with the CB-F7 heteromyeloma cell line. Of these, two antibodies, one IgG and one IgM, bound to myeloperoxidase in solid phase ELISA and gave a perinuclear staining pattern on ethanol-fixed human neutrophil cytospin preparations. The staining patterns were similar to those seen with serum from the patient. Antigen-inhibition studies revealed that the affinity of the IgG monoclonal antibody was 28 times higher (k = 1.4 x 10(-7)) than the IgM antibody (k = 5 x 10(-5)). Cross-inhibition studies further suggested that the two monoclonal antibodies recognized the same epitope on MPO. Of the other secreting cell lines, none produced antibody which reacted with the panel of autoantigens used for testing. Neither mononuclear antibody reacted with this panel indicating that they were not simply polyreactive natural autoantibodies. These are the first human monoclonal antibodies to native myeloperoxidase to be reported.
authors.affiliation: Department of Rheumatology Research, University College and Middlesex Hospital Medical School (UCMSM), London, U.K.
authors.forename: M R
authors.initials: MR
authors.lastname: Ehrenstein
authors.forename: B
authors.initials: B
authors.lastname: Leaker
authors.forename: D
authors.initials: D
authors.lastname: Isenberg
authors.forename: G
authors.initials: G
authors.lastname: Cambridge
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D001167:Arteritis / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis*; D005455:Fluorescent Antibody Technique; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D051379:Mice; D009195:Peroxidase / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009195:Peroxidase