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Abstract
ObjectivesThis study aims to inhibit antiphospholipid syndrome (APS) serum derived IgA anti-beta-2-glycoprotein I (aβ2GPI) binding using Domain I (DI).MethodsSerum from 13 APS patients was tested for IgA aβ2GPI and Anti-Domain I. Whole IgA was purified by peptide M affinity chromatography from positive serum samples. Serum was tested for IgA aβ2GPI binding in the presence and absence of either DI or of two biochemically modified variants containing either 20 kDa of poly(ethylene glycol) (PEG) or 40 kDa of PEG.ResultsSignificant inhibition with DI was possible with average inhibition of 23% (N = 13). Further inhibitions using 20 kDa PEG-DI and 40 kDa PEG-DI variants showed significant inhibition (p = 0.0001) with both the 40 kDa PEG-DI and 20 kDa PEG-DI variants showing increased inhibition compared with DI alone (p = 0.0001 and p = 0.001, n = 10).ConclusionsInhibition of IgA aβ2GPI by DI is possible and can be enhanced by biochemical modification in a subset of patients.
Highlights
Antiphospholipid syndrome (APS) is an autoimmune disorder defined by both laboratory criteria and clinical presentation
In this study we have shown that it is possible to inhibit the binding of both purified and serum IgA from APS patients from binding to b2GPI
The inhibitory effect seen with Domain I (DI) was enhanced by PEGylation
Summary
Antiphospholipid syndrome (APS) is an autoimmune disorder defined by both laboratory criteria and clinical presentation. Three serological criteria for APS are included: IgG and IgM anticardiolipin (aCL) and anti-beta-2-glycoprotein I (ab2GPI) ELISAs, and the lupus anticoagulant test. Whilst IgG and IgM antiphospholipid antibodies (aPL) are well recognized, the importance of IgA aPL is still controversial.[1,2]. IgA aPL has been evaluated in several studies and found even in patients negative for the classical diagnostic antibodies[2,3,4] but who have typical clinical features of APS (seronegative APS). Part of the controversy regarding IgA aCL and ab2GPI is due to the variable prevalence. Article reuse guidelines: sagepub.com/journals-permissions reported in cohorts.[5] Some groups found significant clinical associations with thrombosis and APS diagnosis,[2,6] whilst others did not.[7]
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