No abstract

The objective of this study was to research the functionality of anti-endothelial cell antibodies (AECA) in pulmonary arterial hypertension (PAH) by assessing the effects of IgG from AECA-positive PAH patients on the induction of adhesion molecules on human umbilical vein endothelial cells (HUVECs) and on the production of pro-inflammatory cytokines and chemokines by HUVECs. To achieve this purified IgG from 28 PAH patients were included. IgG from systemic sclerosis (SSc) (n = 58) and systemic lupus erythematosus (SLE) (n = 16) patients without PAH were included as disease controls. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression on HUVECs, incubated with patient IgG, were quantified by flow cytometry. Production of interleukin (IL)-1β, -6, -8, and CC chemokine ligand 2 (CCL2) by HUVECs, incubated with patient IgG, were quantified by multiplex flow cytometry. Our results showed that IgG from AECA-positive PAH, SSc and SLE patients induced significantly higher expression of ICAM-1, VCAM-1, and E-selectin and production of IL-6, -8, and CCL2 compared to IgG from AECA-negative patients and IgG from healthy controls. Like in SLE and SSc, IgG from AECA-positive PAH patients can activate endothelial cells to a pro-adhesive and pro-inflammatory state. Therefore, IgG AECA could play a pathogenic role by inducing inflammatory injury of vascular endothelium which is considered a key player in the initiation and progression of PAH.

SummaryEndothelial cell (EC) apoptosis seems to play an important role in the pathophysiology of pulmonary arterial hypertension (PAH). We aimed to test the hypothesis that circulating anti-endothelial cell antibodies (AECA) of PAH patients induce EC apoptosis. Immunoglobulin (Ig)G was purified from sera of PAH patients (n = 26), patients with systemic lupus erythematosus (SLE) nephritis without PAH (n = 16), patients with systemic sclerosis (