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Anti-Endothelial Cell Antibodies in Pulmonary Arterial Hypertension

DL Cioffi

Karen Fagan


R Morrow

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Conference: 2012 International PHA Conference and Scientific Sessions

Release Date: 06.22.2012

Presentation Type: Abstracts

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease that results in right heart failure. PAH pathology is unclear, but endothelial activation and immune responses contribute to vascular remodeling. Anti-endothelial cell antibodies (AECA) are found in many autoimmune disorders, including both idiopathic and connective tissue disease-associated PAH. In autoimmune vasculitides, AECA activate endothelial cells through increased reactive oxygen species (ROS) production. While the effects of AECA on endothelial cells have been studied in some diseases, the effects of AECA from PAH on pulmonary endothelial cells are unknown. We sought to determine whether AECA bind and increase ROS in pulmonary endothelial cells.

METHODS: To assess antibody binding, Western blots were performed using membrane fractions of human pulmonary and systemic endothelial cells. Blots were treated with serum from PAH patients or healthy controls. IgG was purified from both healthy controls and PAH patients. Confocal fluorescence microscopy was used to visualize IgG binding to fixed cells. Fluorescence microscopy was used to assess the effects of AECA on ROS production in live cells treated with IgG from PAH patients or healthy controls.

RESULTS: While some bands were found in both PAH and healthy subjects, a band of 37 kD was seen in pulmonary microvascular endothelial cells when blots were treated with PAH serum. Confocal microscopy showed that IgG from PAH patients binds to fixed human endothelial cells. Cells treated with IgG from healthy controls showed no increase in ROS, while PAH IgG elicited an increase.

CONCLUSIONS: These data suggest that some AECA from PAH bind to pulmonary endothelial cells and may lead to ROS generation.