Peritoneal autoantibody landscape in endometriosis

Abstract

Women with endometriosis have a profound association with autoimmunity. An excess of autoantigens in the peritoneal cavity resulting from retrograde menstruation could lead to inflammation and pathologic autoimmunity. Using a native-conformation protein array, proteome-wide analysis of autoantibodies (AAbs) against 1623 proteins were profiled in peritoneal fluids (PF) of 25 women with endometriosis and 25 endometriosis-negative women. 46% of endometriotic women have five or more AAbs. Diverse cognate autoantigens were identified and corresponding AAbs against proteins involved in implantation, B-cell activation/development, and aberrant migration and mitogenicity. AAbs recognizing tumour suppressor protein p53 were the most frequent at 35% and were targeted against native and citrullinated p53 forms. Further, unsupervised hierarchical clustering and integrative pathway analysis, we observed clusters of endometriosis-associated infertile women with 60% positive for two or more AAbs which are involved in PDGF, TGF-β, RAC1/PAK1/p38/MMP2 signaling, LAT2/NTAL/LAB-mediated calcium mobilisation and integrin-mediated cell adhesion. Together, our data identifies peritoneal autoimmunity in a significant subset of women with endometriosis, with diverse impact on infertility and disease pathophysiology.