Antiphospholipid antibodies: discovery, definitions, detection and disease

Antiphospholipid antibodies (aPL) are immunoglobulins of IgG, IgM and IgA isotypes that target phospholipid (PL) and/or PL-binding plasma proteins. Detection of aPL in the laboratory is done currently by both immunoassays and functional coagulation tests. Convention defines aPL specificity in immunoassays according to the particular PL substrate present, for example aPS represents antiphosphatidylserine antibodies. This may be technically incorrect inasmuch as a particular PL may be responsible for binding and highly concentrating a specific plasma protein, the latter then becomes the target for the aPL. The binding of beta(2)GP-I (apolipoprotein H) to the negatively charged PL, cardiolipin (CL) provides a good example of this circumstance. In contrast, aPL which specifically prolong coagulation times in in vitro are called lupus anticoagulants (LA). The precise PL target(s) of the aPL responsible for LA activities are unknown and often debated. The persistent finding of aPL in patients in association with abnormal blood clotting and a myriad of neurological, obstetrical and rheumatic disorders often compounded by autoimmune diseases has led to an established clinical diagnosis termed antiphospholipid syndrome (APS). The common denominator for these APS patients is the presence of circulating aPL on two or more occasions and the observation of events attributable to abnormal or accelerated blood clotting somewhere in vivo. The purpose of this review is to collect, collate, and consolidate information concerning aPL.