IgG2 subclass restriction of anti-β2 glycoprotein 1 antibodies in autoimmune patients

Abstract

SUMMARY The IgG subclass and light chain distribution of antiphospholipid antibodies (aPL) occurring in autoimmune patients were determined by means of two radioimmunoassays using either cardiolipinor β2 glycoprotein 1 (β2GP1)-coated microtitre plates and mouse MoAbs. Of 50 sera selected for positivity of anticardiolipin antibodies (ACA) of the IgG isotype, 32 (64%) possessed anti-β2GPl antibodies and their presence was closely associated with clinical features of the antiphospholipid syndrome. Good correlations were found between ACA and anti-β2GP1 antibodies when considering antibody level and patterns of light chain and IgG subclass, suggesting that, overall, the same antibodies were being measured. Light chain analysis showed the polyclonal origin of these antibodies and, in most sera, a trend towards use of λ chain. Among sera positive for anti-β2GP1 antibodies, IgG2 was the major subclass reactive with β2GP1 and cardiolipin (87% and 74β2 of the IgG antibody activity, respectively). In contrast, in the group of 18 sera lacking anti-β2GP1 antibodies, ACA were largely restricted to lgG3, with a lesser contribution by IgGl. A few selected sera from the anti-β2GP1-positive group were shown to contain mixtures of antibodies that required β2GP1 (restricted to IgG2 present in large amounts) and did not require this cofactor (restricted to IgG3 and/or IgG1 present in low amounts) for their reactivity with cardiolipin. There was no contribution of glycosylation to the epitopes recognized by anti-β2GP1 antibodies, even though human anti-carbohydrate antibodies are restricted to the IgG2 subclass. These findings further emphasize the intra- and interindividual heterogeneity of aPL, and should help to discriminate clinically relevant specificies.