Gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome

Abstract

Antiphospholipid antibodies (aPL) cause vascular thrombosis (VT) and/or pregnancy morbidity (PM). Differential mechanisms however, underlying the pathogenesis of these different manifestations of antiphospholipid syndrome (APS) are not fully understood. Therefore, we compared the effects of aPL from patients with thrombotic or obstetric APS on monocytes to identify different molecular pathways involved in the pathogenesis of APS subtypes. VT or PM IgG induced similar numbers of differentially expressed (DE) genes in monocytes. However, gene ontology (GO) analysis of DE genes revealed disease-specific genome signatures. Compared to PM, VT-IgG showed specific up regulation of genes associated with cell response to stress, regulation of MAPK signalling pathway and cell communication. In contrast, PM-IgG regulated genes involved in cell adhesion, extracellular matrix and embryonic and skeletal development. A novel gene expression analysis based on differential variability (DV) was also applied. This analysis identified similar GO categories compared to DE analysis but also uncovered novel pathways modulated solely by PM or VT-IgG. Gene expression analysis distinguished a differential effect of VT or PM-IgG upon monocytes supporting the hypothesis that they trigger distinctive physiological mechanisms. This finding contributes to our understanding of the pathology of APS and may lead to the development of different targeted therapies for VT or PM APS.

Cluster analysis for the identification of clinical phenotypes among antiphospholipid antibody-positive patients from the APS ACTION Registry

“…We found that regardless of any underlying autoimmune diseases, all non-criteria manifestations were gathered in one cluster, suggesting that patients with these manifestations could share a common phenotype, supporting the hypothesis of a common underlying pathologic mechanism. Together with previous data, 25 our results contribute to the understanding of the heterogeneity of clinical phenotypes of APS patients.…”

Blood Cell-Bound C4d as a Marker of Complement Activation in Patients With the Antiphospholipid Syndrome

“…APS patients fulfilled the revised Sapporo criteria (32). The characterization of vascular and obstetric APS was carried out as previously reported (33). Primary ITP was diagnosed according to the International Working Group criteria (34).…”

Estrés oxidativo en células endoteliales inducido por el suero de mujeres con diferentes manifestaciones clínicas del síndrome antifosfolípido

“…Actualmente, se sabe que los anticuerpos antifosfolípidos actúan mediante la formación de un complejo antígeno-anticuerpo en la superficie de diferentes células, el cual podría inducir la activación de diferentes vías de señalización, factores de transcripción, expresión de moléculas de adhesión y expresión de proteínas procoagulantes. Estos eventos en conjunto llevan a un estado trombogénico y proinflamatorio, como se ha demostrado en los estudios in vitro, utilizando células endoteliales, monocitos y plaquetas (4)(5)(6). También, se ha demostrado que los anticuerpos antifosfolípidos inducen efectos en las células trofoblásticas y, como consecuencia, alteran el desarrollo placentario.…”