Targets of anti-endothelial cell antibodies in pulmonary hypertension and scleroderma

Abstract

Anti-endothelial cell antibodies (AECAs) have been identified in patients with systemic sclerosis (SSc) with and without pulmonary arterial hypertension (PAH) and in patients with idiopathic pulmonary arterial hypertension (iPAH). However, their target antigens remain poorly identified.Sera from 24 patients with SSc without PAH, 20 patients with SSc with PAH, 30 with iPAH and 12 healthy controls were collected. Target antigens were identified by two-dimensional electrophoresis and immunoblotting in protein extracts of human umbilical vein endothelial cells. Targeted antigens were identified by mass spectrometry.Serum immunoglobulin G from patients with SSc with or without PAH and patients with iPAH specifically recognised 110, 82 and 37 protein spots, respectively. Among others, target antigens of AECAs included lamin A/C, tubulin b-chain and vinculin. One-dimension immunoblotting experiments confirmed the identification of lamin A/C and tubulin b-chain.In conclusion, our results confirm the presence of AECA in patients with systemic sclerosis with and without pulmonary arterial hypertension and in those with idiopathic pulmonary arterial hypertension, and provide evidence for the identification of target antigens of these autoantibodies including lamin A/C and tubulin b-chain.

Pathogenesis of pulmonary arterial hypertension: lessons from cancer

“…Indeed, a delicate balance between immunity and tolerance exists and any disturbance may result in chronic inflammation or autoimmunity. Several types of autoantibodies directed against antinuclear antigens, endothelial cells and fibroblasts have been found in idiopathic and scleroderma-associated PAH [70][71][72][73]. These autoantibodies seem to play an important role for endothelial cell apoptosis and for the expression of cellular adhesion molecules [74][75][76], and we encourage further studies to characterise their pathogenic importance.…”

Immune Dysregulation and Endothelial Dysfunction in Pulmonary Arterial Hypertension

“…22,23 It is well known that PAH-SSc patients display circulating autoantibodies, but interestingly, it has been reported that a subset of patients with IPAH also display circulating immunoglobulin G-type autoantibodies directed against different components of the vascular wall, ECs, fibroblasts, and SMCs. [24][25][26][27] A recent study has confirmed the prevalence of anti-EC autoantibodies (AECAs) that recognize cell surface components in patients with IPAH (62% prevalence) or associated PAH (78% prevalence). 28 It is also estimated that 30% to 40% of patients with IPAH present antinuclear antibodies and that 10% to 15% of these patients have antiphospholipid antibodies.…”

“…63 Using a proteomic approach, Dib and coworkers 25 were recently able to identify target antigens for AECAs in IPAH, which include lamin A/C and tubulin β-chain, major components of the inner nuclear membrane and microtubules, respectively. These proteins identified as targets of AECAs are ubiquitous and play key roles in different cell types in that they are involved in cell metabolism, morphology, and protein folding, but the exact role of AECAs in patients with IPAH remains unclear.…”

Molecular pathogenesis of pulmonary arterial hypertension

“…Tertiary lymphoid tissue was described in patients with IPAH as evidence of altered immune regulation (106). Similarly, circulating autoantibodies are observed in patients with both autoimmune and idiopathic and other associated forms of pulmonary hypertension, but the role of these antibodies in the pathology is the subject of considerable investigation (107).…”