IGG2 SUBCLASS RESTRICTION OF ANTI-BETA(2) GLYCOPROTEIN-1 ANTIBODIES IN AUTOIMMUNE PATIENTS

The IgG subclass and light chain distribution of antiphospholipid anti bodies (aPL) occurring in autoimmune patients were determined by means of two radioimmunoassays using either cardiolipin-or beta(2) glycopro tein 1 (beta(2)GP1)-coated microtitre plates and mouse MoAbs. Of 50 se ra selected for positivity of anticardiolipin antibodies (ACA) of the IgG isotype, 32 (64%) possessed anti-beta(2)GP1 antibodies and their p resence was closely associated with clinical features of the antiphosp holipid syndrome. Good correlations were found between ACA and anti-be ta(2)GP1 antibodies when considering antibody level and patterns of li ght chain and IgG subclass, suggesting that, overall, the same antibod ies were being measured. Light chain analysis showed the polyclonal or igin of these antibodies and, in most sera, a trend towards use of lam bda, chain. Among sera positive for anti-beta(2)GP1 antibodies, IgG2 w as the major subclass reactive with beta(2)GP1 and cardiolipin (87% an d 74% of the IgG antibody activity, respectively). In contrast, in the group of 18 sera lacking anti-beta(2)GP1 antibodies, ACA were largely restricted to IgG3, with a lesser contribution by IgG1. A few selecte d sera from the anti-beta(2)GP1-positive group were shown to contain m ixtures of antibodies that required beta(2)GP1 (restricted to IgG2 pre sent in large amounts) and did not require this cofactor (restricted t o IgG3 and/or IgG1 present in low amounts) for their reactivity with c ardiolipin. There was no contribution of glycosylation to the epitopes recognized by anti-beta(2)GP1 antibodies, even though human anti-carb ohydrate antibodies are restricted to the IgG2 subclass. These finding s further emphasize the intra- and interindividual heterogeneity of aP L, and should help to discriminate clinically relevant specificies.