Antiphospholipid Antibody Panel

Lupus anticoagulant comprises immunoglobulins that bind phospholipid-dependent coagulation reactions in vitro, paradoxically prolonging clotting times in laboratory tests whilst promoting thrombosis in vivo. Despite its name, lupus anticoagulant is neither specific to systemic lupus erythematosus nor an anticoagulant clinically. Detection relies on functional clotting assays — dilute Russell viper venom time or activated partial thromboplastin time — that demonstrate prolongation not corrected by mixing with normal plasma but corrected or attenuated by excess phospholipid, a pattern that distinguishes antibody from factor deficiency.

Lupus anticoagulant is the antiphospholipid antibody most strongly associated with thrombosis and pregnancy morbidity. Its presence defines laboratory criteria for antiphospholipid syndrome when detected on two occasions at least twelve weeks apart alongside clinical events, and it carries greater thrombotic risk than anticardiolipin or anti-β2-glycoprotein-I antibodies alone.

Anticardiolipin antibodies recognise complexes of cardiolipin — a negatively charged phospholipid — and the plasma protein β2-glycoprotein-I. The IgG isotype is measured by enzyme-linked immunosorbent assay, and titre is reported in GPL units (IgG phospholipid units), a semi-quantitative convention standardised to international reference sera. Low-positive titres are common and often transient; moderate-to-high persistent titres correlate better with thrombotic and obstetric risk.

Moderate-to-high titre IgG anticardiolipin, confirmed on repeat testing twelve weeks apart, forms part of the laboratory criteria for antiphospholipid syndrome. The antibody can appear transiently after infection or be seen in autoimmune disease without thrombosis, so clinical context and persistence are essential to interpretation.

The IgM isotype of anticardiolipin antibodies is measured in parallel with IgG, reported in MPL units (IgM phospholipid units). IgM antibodies can be induced by infection and are often transient, so their clinical significance is lower than that of IgG unless titres are high and persistent.

IgM anticardiolipin at moderate-to-high titre, confirmed on repeat, may contribute to antiphospholipid syndrome diagnosis but is weighted less heavily than IgG or lupus anticoagulant. Isolated IgM positivity without IgG or LA is more likely to be transient or non-pathogenic.

β2-Glycoprotein-I is the principal protein cofactor for antiphospholipid antibodies. Antibodies directed against β2GPI itself, rather than the cardiolipin-β2GPI complex, are detected by ELISA and reported in standardised IgG units. These antibodies recognise epitopes on domain I of the protein and are thought to be the pathogenic species driving thrombosis and pregnancy loss.

Anti-β2GPI IgG at moderate-to-high titre is part of the laboratory criteria for antiphospholipid syndrome when confirmed on repeat and is independently associated with thrombosis and adverse pregnancy outcomes. Some evidence suggests anti-β2GPI IgG may be more specific for true APS than anticardiolipin alone.

The IgM isotype of anti-β2-glycoprotein-I antibodies is measured alongside IgG. As with anticardiolipin IgM, the clinical significance of isolated IgM anti-β2GPI is uncertain, and transient positivity after infection is well documented.

IgM anti-β2GPI may support the diagnosis of antiphospholipid syndrome when titres are high and persistent, but isolated IgM positivity is less clearly pathogenic and should prompt repeat testing and clinical correlation.