Background/Purpose: The current APS Classification Criteria recommend testing for IgG and IgM antibodies for β₂glycoprotein I (β₂GPI), and do not differentiate between primary and secondary APS. This study was designed to investigate the clinical performance of different β₂GPI IgG, IgM and IgA antibody tests in a SLE with arterial and/or venous thrombosis.

Methods: IgG, IgM, and IgA anti-β₂GPI antibodies were determined in 200 patients from a lupus cohort with 3 ELISA (Bio-Rad, Corgenix and INOVA) and 1 fluoro-enzyme immunoassay commercial kits (Phadia), following the manufacturers’ instructions. Kits were provided at no cost by the manufacturers, and assays were performed at ARUP laboratories.  The degree of agreement between the different kits was quantified using a Kappa statistic.  Univariate and multivariate analyses were performed to assess the association between kit results and lifetime history of venous or arterial thrombosis. 

Results:

The pairwise agreement between the different kits was high for IgG and IgM with Kappa coefficients ranging from 0.64 to 0.98 and 0.74 to 0.93 respectively.  This measure was somewhat lower for IgA with Kappa coefficients ranging from 0.24 to 0.78. Twenty-seven (14%) had a history of venous thrombosis.  For all assays and all kits, those with a positive assay result were more likely to have a history of venous thrombosis than those with a negative assay result.  These differences reached statistical significance in univariate and multivariate analyses of IgG and IgA, adjusted for age, race, and anti-htn medications.  The observed differences were not statistically significant for IgM, in part due to the relatively small number of patients positive for IgM. Thirty-four patients (17 %) had a history of arterial thrombosis. There was not strong evidence of an association between the assay results and arterial thrombosis.

Table 1:  Proportion(%) with a history of Venous Thrombosis by antibody status.

¹ Fisher’s Exact Test

^2.Based on Logistic Regression, controlling for age and race, and anti-htn medications.

Table 2:  Proportion (%) with a history of Arterial Thrombosis by antibody status

¹ Fisher’s Exact Test

^2.Based on Logistic Regression, controlling for age, race, and anti-htn medications.

Conclusion:

Only IgG and IgA isotypes were associated with venous thrombosis in SLE, using the p-value adjusted for age and ethnicity. Although the IgA kits showed variable agreements, our data indicate that testing for β₂ GPI IgA isotype   may be of clinical relevance in the evaluation of venous thrombosis in APS associated with SLE.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/only-igg-and-iga-%ce%b22glycoprotein-i-antibody-isotypes-are-associated-with-venous-thrombosis-in-systemic-lupus-erythematosus/