Autoimmunity and pulmonary hypertension: a perspective

Abstract

The association between autoimmunity and pulmonary arterial hypertension (PAH) has been appreciated for .40 yrs, but how autoimmune injury might contribute to the pathogenesis of this disease has only been examined in a case-specific manner.It is becoming increasingly clear that a variety of diverse clinical diseases, ranging from viral infections to connective tissue disorders, can culminate in pulmonary vascular pathology that is indistinguishable. Is there a hitherto unappreciated biology that unites these seemingly unrelated conditions?The answer to this question may come from the increasing body of evidence concerned with the central importance of regulatory T-cells in preventing inappropriate B-cell activity. Two striking similarities between conditions associated with severe angioproliferative pulmonary hypertension are a defect in the CD4 T-cell compartment and auto-antibody production. Pathogenic autoantibodies targeting endothelial cells are capable of inducing vascular endothelial apoptosis and may initiate the development of PAH.The present review will focus on what is known about autoimmune phenomena in pulmonary arterial hypertension patients, in order to better consider whether an early loss of self-tolerance followed by autoimmune injury could influence the early development of severe angioproliferative pulmonary hypertension.

Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

“…Antibodies have also been reported in SSc-PAH, including fibrin-bound tissue plasminogen activator in patients with limited cutaneous SSc, and in patients with IPAH with HLA-DQ7 antigen (32), and anti-topoisomerase IIa antibodies, particularly in association with HLA-B35 antigen (33). Anti-EC antibodies can activate EC, induce the expression of adhesion molecules, and trigger apoptosis (34). In vitro, autoantibodies from patients with connective tissue diseases (anti-U1-ribonucleoprotein and anti-ds-DNA) can up-regulate adhesion molecules and histocompatibility complex class II molecules on human pulmonary arterial EC (35), suggesting that inflammation could lead to pulmonary proliferative vasculopathy.…”

Systemic Sclerosis-associated Pulmonary Arterial Hypertension

“…19 In SSc-PAH, autoimmune dysregulation may also be preponderant. 20 For example, a study by Riemekasten et al 21 showed that angiotensin II type-1 receptor antibodies and endothelin-1 receptor type A antibodies were present in most patients with SSc. In vitro, these antibodies upregulated infl ammatory mediators and increased cytotoxicity, suggesting a signifi cant role in vascular remodeling.…”

STILL out of Breath?

“…The inflammatory process thus induced with the release of cytokines and growth factors by these cells may contribute to the vascular remodeling seen in these patients. Furthermore, some reports advocate a role of autoimmunity in the pathologic genesis of PAH [32]. Cases of regression of PAH with treatment of the underlying inflammatory process gives more weight to this argument.…”