Abstract 16764: Locally Produced SAMHD1 Immune Complexes Are Associated With the Development of Idiopathic Pulmonary Arterial Hypertension

Introduction: Autoimmunity has been related to the pathophysiology of idiopathic pulmonary arterial hypertension (IPAH). We previously reported 35 IPAH-related antigens identified in immune complexes (ICs) in lungs from IPAH patients. Among these antigens, we validated increased ICs containing SAMHD1, an HIV1 restriction factor, in IPAH vs. donor control lungs. Hypotheses: We hypothesized that 1) viruses and/or inflammatory stimuli increase SAMHD1, which is released in exosomes and induces local production of antibodies, 2) SAMHD1 ICs are observed in experimental inflammatory pulmonary hypertension (PH) induced by monocrotaline (MCT) in rats. Methods: The viral signature of IPAH vs. control lung tissue was determined by high-throughput sequencing and validated by qPCR. Localization of SAMHD1 or SAMHD1 antibodies was determined by immunohistochemistry. Protein expression was analyzed by western blot in lung tissue and in pulmonary arterial endothelial cells (PAEC) stimulated with TNFα. Experimental PH was ...