Immunoglobulin G anti-endothelial cell antibodies: Inducers of endothelial cell apoptosis in pulmonary arterial hypertension?

S. J. Arends*, J. G.M.C. Damoiseaux, A. M. Duijvestijn, L. Debrus-Palmans, M. Vroomen, K. A. Boomars, H. P. Brunner-La Rocca, C. P.M. Reutelingsperger, J. W. Cohen Tervaert, P. Van Paassen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

26 Citations (Scopus)

Abstract

Endothelial 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 (SSc) without PAH (n=58) and healthy controls (n=14). Human umbilical vein endothelial cells (HUVECs) were incubated with patient or healthy control IgG for 24h. Thereafter, apoptosis was quantified by annexin A5 binding and hypoploid cell enumeration by flow cytometry. Furthermore, real-time cell electronic sensing (RT-CES™) technology was used to monitor the effects of purified IgG from patient and healthy control IgG on HUVECs. As demonstrated previously, IgG of AECA-positive SLE nephritis patients (n=7) induced a higher percentage of apoptosis of HUVECs compared to IgG of AECA-negative SLE nephritis patients and healthy controls. Furthermore, IgG of AECA-positive SLE nephritis patients induced a marked decrease in cell index as assessed by RT-CES™ technology. IgG of AECA-positive PAH patients (n=12) and SSc patients (n=13) did not alter the percentage of HUVEC apoptosis or cell index compared to IgG of AECA-negative PAH and SSc patients and healthy controls. AECA-positive PAH patients, in contrast to SLE nephritis patients, do not have circulating IgG AECA that enhances apoptosis of HUVECsin vitro. Further studies should focus on other mechanisms by which AECA may enhance EC apoptosis in PAH, such as antibody-dependent cell-mediated cytotoxicity.

Original languageEnglish
Pages (from-to)433-440
Number of pages8
JournalClinical and Experimental Immunology
Volume174
Issue number3
DOIs
Publication statusPublished - Dec 2013
Externally publishedYes

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