Beta-2-Glycoprotein I-Domain 1 Antibody (IgG)

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial, venous, or microvascular thrombosis, pregnancy morbidity, or nonthrombotic manifestations in patients with persistent antiphospholipid antibodies (aPL).

In 2023, the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) published an update to the classification of APS.¹ The new criteria include 1 positive aPL test within 3 years of identifying an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into 6 clinical domains and 2 laboratory domains (Table). Patients accumulating at least 3 points each from the clinical and laboratory domains are classified as having APS.

Compared to the 2006 revised Sapporo classification criteria,² the 2023 ACR/EULAR APS classification had an improved specificity of 99% versus 86% but a reduced sensitivity of 84% versus 99%, respectively.

Beta-2-glycoprotein I (also known as β₂-glycoprotein I)-domain 1 IgG antibodies are a special subset of beta-2-glycoprotein I IgG antibodies. Beta-2-glycoprotein I antibodies have been reported to bind to epitopes located primarily on domains 1, 4, and 5 of the beta-2-glycoprotein I molecule.³ The main beta-2-glycoprotein I epitope specifically associated with APS has been reported to be a cryptic and conformation-dependent structure that involves different regions of domain 1.⁴ Results are reported in chemiluminescence units (CU).

The assay is intended for the detection of IgG antibodies to domain 1 of β₂-glycoprotein I in serum or plasma and is provided as a stand-alone test or a reflex test when beta-2-glycoprotein I IgG antibodies are detected (at additional charge). The presence of beta-2-glycoprotein I-domain 1 autoantibodies is used in conjunction with clinical and other laboratory findings as an aid in the diagnosis of APS. The assay is not intended to replace assays for antibodies against the whole beta-2-glycoprotein I molecule.⁵

A positive beta-2-glycoprotein I-domain 1 IgG antibody test result may be helpful in identifying patients at increased risk for arterial and venous thrombosis and pregnancy morbidity.⁶ Furthermore, patients who have “triple positivity” of criteria antibodies, defined as positivity for lupus anticoagulant, cardiolipin, and beta-2-glycoprotein I antibodies (associated with increased thrombosis risk), are at further risk of thrombosis when beta-2-glycoprotein I-domain 1 IgG antibodies are present.^{7, 8}

Lastly, patients who are positive for both phosphatidylserine/prothrombin antibodies (also useful for thrombosis risk stratification, see FAQ 262: Phosphatidylserine-Prothrombin Antibodies, IgG, IgM  and beta-2-glycoprotein I-domain 1 IgG antibodies have even higher risk for thrombosis than those with positivity for either antibody alone.^9-11

The designated IgG cutoff of ≤19 CU is an optimal cutoff for sensitivity and specificity for APS based on the test manufacturer’s studies. This cutoff may represent the 99th percentile of the normal population, depending on the characteristics of the normal population studied.⁵

No. Beta-2-glycoprotein I-domain 1 IgG antibody testing is performed using a chemiluminescence immunoassay, and anticoagulants do not interfere with testing. Therefore, beta-2-glycoprotein I-domain 1 IgG antibody test results are not affected by anticoagulants such as vitamin K antagonists (eg warfarin), heparins (low molecular weight and unfractionated), direct thrombin inhibitors (eg, dabigatran), or anti-Xa medications (eg, rivaroxaban, apixaban, edoxaban). In contrast, as noted above, anticoagulants may affect the results of lupus anticoagulant testing (depending on the level of and type of anticoagulant).¹²