β₂-Glycoprotein 1 Antibodies, IgA, IgG, IgM

Recently, an international consensus group of experts in the diagnosis and management of antiphospholipid syndrome (APS) concluded that β₂-GP1 IgG and IgM antibodies should be included as diagnostic criteria for APS.² This group determined that the presence of one or both of these antibodies is an independent risk factor for thrombosis and pregnancy complications.³

A common aspect to all assays for anticardiolipin antibodies (ACA) is the requirement that the assay system include a source of plasma proteins.³ It has been determined that, in many patients, β₂-glycoprotein 1 (β₂-GP1) is the plasma factor required for ACA binding.^3,4 Solid-phase enzyme immunoassays that detect antibodies that bind to β₂-GP1 in the absence of phospholipid are now part of the diagnostic arsenal for APS. β₂-GP1-dependent binding is frequently detected in patients with clinical symptoms of APS.³ All three isotypes of anti-β₂-GP1 (IgG, IgM, and IgA) have been associated with thrombosis.^3,5,6 ACA that do not require β₂-GP1 are usually transient and not clinically significant. Studies have shown that ACA associated with infections tend to not be β₂-GP1-dependent.⁴ This supports the conclusion that anti-β₂-GP1 assays may be more specific for APS than ACA.^4,7,8 While the majority of patients with LA will also test positive for ACA and β₂-GP1 antibodies, approximately 30% of patients tested will have discordant results.^9,10 Approximately 20% of patients who test negative for ACA will test positive for β₂-GP1.⁹ Anti-β₂-GP1 testing can be useful in the evaluation of patients with positive ACA results and a clinical picture that is not consistent with APS.^3,4,8 A negative anti-β₂-GP1 result in this context would not support a diagnosis of APS. Anti-β₂-GP1 testing can also support the diagnosis of APS in patients with a strong clinical picture for APS with negative LA and ACA results.⁸