SPECIES-SPECIFICITY OF ANTI-BETA(2) GLYCOPROTEIN-I AUTOANTIBODIES ANDITS RELEVANCE TO ANTICARDIOLIPIN ANTIBODY QUANTITATION

Some patients suspected of having antiphospholipid antibody syndrome ( APS) were found to be positive for anti-beta(2) glycoprotein I (beta(2 )GPI) antibodies despite negative results for antibodies to cardiolipi n (ACA). Since the major source of beta(2)GPI in the ACA assay is anim al (usually bovine) serum, we studied the influence on ACA quantitatio n of the species specificity of anti-beta(2)GPI antibodies from patien ts with various autoimmune disorders, mostly systemic lupus erythemato sus and primary APS. Ninety-seven sera were selected based on IgG (n = 76) or IgM (n = 64) positivity by ELISA using gamma-irradiated plates coated with human or bovine purified beta(2)GPI. A higher proportion of IgM (43.7%) than IgG (7.9%) reacted to human, but not bovine, beta( 2)GPI. Furthermore, from the samples reactive to both proteins, the ra tio of antibody level against bovine to that against human beta(2)GPI was 1.08 +/- 0.58 for IgG and 0.58 +/- 0.3 for IgM (p <10(-5)). IgG an d IgM ACA were detected in 78 and 40 sera, respectively; concordance b etween the two ELISAs for ACA and anti-beta(2)GPI antibodies was 94% f or IgG and 75% for IgM. Out of 28 IgM showing recognition restricted t o human beta(2)GPI, 21 were missed by the ACA assay, possibly because of lower concentrations of beta(2)GPI in those patients' sera. The ant ibody reactivity pattern towards human and bovine beta(2)GPI of indivi dual sera showed no variation with time and was related to the relativ e antibody avidity for each protein. A murine anti-human beta(2)GPI mo noclonal antibody, 9G1; that cross-reacts with bovine beta(2)GPI, comp eted to a large extent with the patients' anti-beta(2)GPI antibody bin ding sites whatever isotype involved or protein recognized. Therefore, anti-beta(2)GPI antibodies of IgM isotype display a marked preference for human compared to bovine beta(2)GPI responsible for frequent inco nsistencies in the ACA assay.