Prevalence of anti-endothelial cell antibodies in idiopathic pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare disease often resulting in right-sided heart failure and premature death [1]. PAH is idiopathic (IPAH), heritable, or related to conditions such as connective tissue diseases (CTD) [2]. IPAH prognosis remains poor despite improved patient survival with current treatment options. Therefore, elucidating the pathophysiology of IPAH is important for the discovery of novel therapeutic approaches. Inflammation and immune reactivity have been implicated in the pathophysiology of IPAH. In 2005, TAMBY et al. [3] described the presence of anti-endothelial cell antibodies (AECA) in IPAH, pointing at the involvement of humoral immunity. AECA are a heterogeneous family of auto-antibodies capable of reacting with different endothelial cell (EC) structures [4]. In PAH, pulmonary EC dysfunction is considered a key player in the initiation and progression of the disease [5]. Systemic sclerosis (SSc) is a paradigm of autoimmune PAH, as 10–15% of these patients develop PAH [6]. Interestingly, in SSc, immunoglobuliln (Ig)G AECA targeting cell-surface antigens have indeed been shown to induce EC dysfunction [7, 8]. Thus, IgG AECA-induced endothelial dysfunction may be the initiating event in IPAH. Whereas IgG auto-antibodies are considered pathogenic in various autoimmune diseases, IgM auto-antibodies have been proposed to be protective in these diseases [9].