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Arthritis Rheum. 2013 Dec;65(12):3186-93. doi: 10.1002/art.38131.

Value of isolated IgA anti-β2 -glycoprotein I positivity in the diagnosis of the antiphospholipid syndrome.

Author information

1
University of Texas Medical Branch, Galveston.

Abstract

OBJECTIVE:

To examine the prevalence of isolated IgA anti-β2 -glycoprotein I (anti-β2 GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of β2 GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-β2 GPI in a mouse model of thrombosis.

METHODS:

Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n = 558), patients with SLE from the Hopkins Lupus Cohort (n = 215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n = 5,098) were evaluated. IgA anti-β2 GPI titers and binding to domain IV/V of β2 GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-β2 GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity.

RESULTS:

A total of 198 patients were found to be positive for IgA anti-β2 GPI isotype, and 57 patients were positive exclusively for IgA anti-β2 GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-β2 GPI-positive serum samples reacted with domain IV/V of anti-β2 GPI, and 77% of those had clinical features of APS. Isolated IgA anti-β2 GPI positivity was associated with an increased risk of arterial thrombosis (P < 0.001), venous thrombosis (P = 0.015), and all thrombosis (P < 0.001). The association between isolated IgA anti-β2 GPI and arterial thrombosis (P = 0.0003) and all thrombosis (P = 0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-β2 GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls.

CONCLUSION:

Isolated IgA anti-β2 GPI-positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid tests are negative and APS is suspected is recommended. IgA anti-β2 GPI antibodies directed to domain IV/V of β2 GPI represent an important subgroup of clinically relevant antiphospholipids.

PMID:
23983008
PMCID:
PMC4048705
DOI:
10.1002/art.38131
[Indexed for MEDLINE]
Free PMC Article

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