How do antiphospholipid antibodies bind β2‐glycoprotein I?

The debate as to the nature and sites of the major epitopes on β2GPI is likely to continue. Since aPL are heterogeneous, it is not surprising that different results have been obtained by different groups, and it is likely that different antibodies recognize epitopes on different domains. The balance of the most persuasive evidence from crystallography, clinical studies, and studies of domain-deleted mutants of β2GPI points to the existence of a major noncryptic epitope on domain I. This epitope may represent the best target for a drug designed to inhibit the aPL-β2GPI interaction which would thus ameliorate APS.