title: Identification and characterization of antimitochondrial autoantibodies in sera of patients with monoclonal gammopathies.
abstract: Monoclonal gammopathies (MG) are defined by the accumulation of monoclonal immunoglobulins, a result of monoclonal B lymphocytes or plasma cell proliferative disorder. Only rarely do these antibodies cause an overt disease by binding to a specific autoantigen (e.g., factor VIII). In the present study, sera from 100 patients with MG were screened for the presence of antibodies against the mitochondrial pyruvate dehydrogenase complex (PDH) -- autoantibodies that are the hallmark primary biliary cirrhosis (PBC). Anti-PDH antibodies were found in 6 patients, all asymptomatic. Using ELISA and immunoblotting methods, it was found that the titre of the anti-PDH antibodies was relatively low (average OD +/- SD: 0.744 +/- 0.529; PBC patients: 1.225 +/- 0.291; P = 0.02). In each patient the autoantibodies were of both kappa and lambda chains, suggesting that they are of polyclonal origin and implying that in MG there is a significant production of polyclonal autoantibodies, in addition to monoclonal proliferation. Furthermore, in 5 of the 6 patients (83%) the anti-PDH antibodies did not recognize the E2 component of PDH (which is the major autoantigen in PBC) an did not inhibit the activity of PDH (which was inhibited by PBC autoantibodies). This is in concert with the fact that none of the patients developed liver disease and emphasizes the specificity of the anti-PDH autoantibodies associated with PBC.
authors.affiliation: Department of Medicine B, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Gilbrud
authors.forename: P
authors.initials: P
authors.lastname: Weiss
authors.forename: R
authors.initials: R
authors.lastname: Bakimer
authors.forename: Y
authors.initials: Y
authors.lastname: Shoenfeld
mesh_terms: D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000032:analysis / Q000097:blood*; D002384:Catalysis; D000939:Epitopes / Q000097:blood; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000097:blood; D007146:Immunoglobulin lambda-Chains / Q000097:blood; D008928:Mitochondria / Q000737:chemistry / Q000276:immunology*; D010265:Paraproteinemias / Q000097:blood / Q000276:immunology*; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors / Q000097:blood / Q000276:immunology
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D011768:Pyruvate Dehydrogenase Complex