Measuring IgA Anti-β2-Glycoprotein I and IgG/IgA Anti-Domain I Antibodies Adds Value to Current Serological Assays for the Antiphospholipid Syndrome

Abstract

IntroductionCurrently available clinical assays to detect antiphospholipid antibodies (aPL) test for IgG and IgM antibodies to cardiolipin (aCL) and β2-glycoprotein I (aβ2GPI). It has been suggested that testing for IgA aPL and for antibodies to Domain I (DI), which carries the key antigenic epitopes of β2GPI, could add value to these current tests. We performed an observational, multicenter cohort study to evaluate the utility of IgG, IgM and IgA assays to each of CL, β2GPI and DI in APS.MethodsSerum from 230 patients with APS (n = 111), SLE but not APS (n = 119), and 200 healthy controls were tested for IgG, IgM and IgA aCL, aβ2GPI and aDI activity. Patients with APS were further classified into thrombotic or obstetric APS. Logistic regression and receiver operator characteristic analyses were employed to compare results from the nine different assays.ResultsAll assays displayed good specificity for APS; IgG aCL and IgG aβ2GPI assays however, had the highest sensitivity. Testing positive for IgA aβ2GPI resulted in a higher hazard ratio for APS compared to IgM aβ2GPI. Positive IgG, IgM or IgA aDI were all associated with APS, and in subjects positive for aCL and/or aβ2GPI, the presence of aDI raised the hazard ratio for APS by 3–5 fold. IgG aCL, aβ2GPI, aDI and IgA aDI were associated with thrombotic but not obstetric complications in patients with APS.ConclusionMeasuring IgG aDI and IgA aβ2GPI and aDI may be useful in the management of patients with APS, particularly thrombotic APS.

Incidence of thromboembolic events in asymptomatic carriers of IgA anti ß2 glycoprotein-I antibodies

“…[37, 38] Our work also contributes to solving the third problem: defining the significance of isolated positivity of IgA with aB2GPI in asymptomatic population.…”

Seronegative antiphospholipid syndrome: refining the value of “non-criteria” antibodies for diagnosis and clinical management

“…33 A second study evaluated, in addition to IgM and IgG, the positivity and predictivity of IgA aCL and IgA aβ2GPI in 430 patients: 111 with APS, 119 with SLE, and 200 healthy controls. 34 Positivity for IgA aCL was 38%; IgA aβ2GPI was 46% in patients with APS. All three antibody isotypes (IgM, IgG and IgA) were significantly associated with a diagnosis of APS, with high specificity but not good sensitivity, based on receiver operating characteristic (ROC) analysis.…”

Recent advances in understanding antiphospholipid syndrome

“…A recent study in aCL and/or aβ2GPI positive patients suggests that the added finding of anti-DI positivity makes it three to five times more likely to confirm APS. Positivity for IgG or IgA (but not IgM) anti-DI increased the strength of association between aCL/aβ2GPI and thrombotic manifestations in APS 19 .…”