Proteomic Characterization of the Placental Proteome in Pregnant Systemic Lupus Erythematosus Patients

Abstract ID 97583 Poster Board 434 Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disease (AD) characterized by non-specific, whole-body manifestations. The disease demonstrates a clear sex bias, disproportionately affecting women of child-bearing age; in fact, SLE occurs at a rate of 9:1 in females compared to males. Consequently, understanding the intersection of pregnancy and SLE is pivotal to providing adequate care to this population. It is well understood that SLE patients are at higher risk for adverse pregnancy outcomes such as preterm birth and fetal loss. In fact, disease flares are common during pregnancy and the incidence of preeclampsia (PE) is increased, affecting up to 30% of patients. Consequently, prescription of medications is necessary to manage disease symptoms and mitigate maternal-fetal morbidity. Recent work in our laboratory demonstrated that SLE significantly affects drug transporter expression in the placenta, altering drug disposition. Characterization of placental damage in SLE pregnancies beyond transport proteins can therefore help inform care and improve patient outcomes. Objective and Hypothesis: Proteomics is a powerful tool that can uncover underlying mechanisms of disease and provide an unbiased picture of disease activity. However, no proteomic studies on placental tissue in SLE pregnancies have been performed. As such, we aimed to use the technique to holistically characterize the effects of this AD on the placenta. We hypothesize that SLE will have a marked effect on the placental proteome. Methods: Placenta from gestational age matched healthy and SLE patients (n = 6) were collected from the RWCIH biobank in accordance with the research ethics boards at the University of Toronto. Protein was extracted and subject to a previously described filter-aided sample preparation, digested, acidified and desalted. 1ng of peptide was loaded onto an Orbitrap HPLC-MS/MS in duplicate and run using a data dependent acquisition method. The raw files were uploaded to MaxQuant and outputs were processed using Perseus, G-profiler and Cytoscape for statistical analyses and data visualization. Results: SLE has a significant effect on the placental proteome, indicating altered organ function due to damage. Over 1500 proteins were identified, 216 of which were differentially expressed between control and SLE samples (p < 0.05, FDR = 0.05 [S = 0.1]). Differentially expressed proteins demonstrated similarities to those previously reported in SLE as changed, including endoglin (159% increase) and alpha-1-acid glycoprotein (63% increase), indicating a conserved effect of the disease on diverse organ systems. Functional enrichment analysis demonstrated that pathways including inflammation, apoptosis, oxidative stress, and angiogenesis were altered in the placenta of SLE patients. Interestingly, these processes are similarly enriched in PE patients, and are highly correlated to poor pregnancy outcomes. Conclusions: As the first study to use proteomics to investigate the direct placental implications of SLE, this work can act as an excellent starting point to improving maternal-fetal outcomes. Identification of changes in the expression of various proteins and their correlated biological roles can inform new potential therapeutic targets for these patients and adjustments to current treatment plans. This work was supported by an operating grant from the Canadian Institutes of Health Research (CIHR) awarded to Piquette-Miller [PJT-169195].