Circulating immune-complexes of IgG/IgM bound to B2-glycoprotein-I associated with complement consumption and thrombocytopenia in antiphospholipid syndrome

Abstract

BackgroundAntiphospholipid syndrome (APS) is a multisystemic autoimmune disorder characterized by thrombotic events and/or gestational morbidity in patients with antiphospholipid antibodies (aPL). In a previous single center study, APS-related clinical manifestations that were not included in the classification criteria (livedo reticularis, thrombocytopenia, leukopenia) were associated with the presence of circulating immune-complexes (CIC) formed by beta-2-glycoprotein-I (B2GP1) and anti-B2GP1 antibodies (B2-CIC). We have performed a multicenter study on APS features associated with the presence of B2-CIC.MethodsA multicenter, cross-sectional and observational study was conducted on 303 patients recruited from six European hospitals who fulfilled APS classification criteria: 165 patients had primary APS and 138 APS associated with other systemic autoimmune diseases (mainly systemic lupus erythematosus, N=112). Prevalence of B2-CIC (IgG/IgM isotypes) and its association with clinical manifestations and biomarkers related to the disease activity were evaluated.ResultsB2-CIC prevalence in APS patients was 39.3%. B2-CIC-positive patients with thrombotic APS presented a higher incidence of thrombocytopenia (OR: 2.32, p=0.007), heart valve thickening and dysfunction (OR: 9.06, p=0.015) and triple aPL positivity (OR: 1.83, p=0.027), as well as lower levels of C3, C4 and platelets (p-values: <0.001, <0.001 and 0.001) compared to B2-CIC-negative patients. B2-CIC of IgM isotype were significantly more prevalent in gestational than thrombotic APS.ConclusionsPatients with thrombotic events and positive for B2-CIC had lower platelet count and complement levels than those who were negative, suggesting a greater degree of platelet activation.

Differences in Antiphospholipid Antibody Profile between Patients with Obstetric and Thrombotic Antiphospholipid Syndrome

“…This observation associated with the finding that whereas thrombotic APS displayed more IgG aPL reactivities than obstetric APS, IgM aPL reactivities were more prevalent in OAPS. The idea that IgM isotypes are more prevalent in gestational than thrombotic APS, and vice versa, was also observed recently in a study describing the prevalence of circulating β2GPI-aβ2GPI immune complexes [ 36 ].…”

ARID5B‐mediated LINC01128 epigenetically activated pyroptosis and apoptosis by promoting the formation of the BTF3/STAT3 complex in β2GPI/anti‐β2GPI‐treated monocytes

“…In line with this, our data showed that patients with PAPS with triple positivity had fewer PLT compared to that in non‐triple‐positive patients. Complement levels are associated with the disease activity of APS 63,64 . Studies have shown that the levels of C3 and C4 are decreased in patients with APS with thrombotic events, 63 and the reduced complement levels are associated with the increased risk of APOs 64 .…”

The role of monocytes in thrombotic diseases: a review

“…The proteome of monocytes treated with thrombotic APS IgG was further described using label-free proteomics. Among the 12 most reliable proteins associated with the cytoskeleton, immune response, and coagulation function, POTEE and b-actin-like protein 3 overlapped with 2D DiGE, Abnormalities in the regulation of these proinflammatory and procoagulant proteins could serve as targets for subsequent treatment and contribute to a deeper understanding of the diversity of APS pathogenesis (186). Urine proteomics has recently been reported as a noninvasive method to distinguish primary thrombotic APS from primary obstetric APS.…”