Anti-ET_AR and anti-AT₁R autoantibodies are elevated in patients with endstage cystic fibrosis

Autoantibodies against endothelin-1 type A receptor (ET_AR) are present in systemic sclerosis complicated by lung fibrosis and pulmonary hypertension. As increased serum levels and local overproduction of endothelin-1 in the airways are reported in cystic fibrosis (CF) patients, we reasoned that anti-ET_AR antibodies could be prevalent in endstage CF patients prior to lung transplantation (LTx). Also, ET_AR autoantibodies are frequently associated with autoantibodies against the angiotensin II type 1 receptor (AT₁R). We analyzed the presence of anti-ET_AR and anti-AT₁R autoantibodies in 43 LTx patients (chronic obstructive pulmonary disease (COPD), n=20; CF, n=13; interstitial lung disease (ILD), n=1). We observed overall higher anti-ET_AR and anti-AT₁R autoantibody titers in sera taken prior to LTx in the CF patient group as compared to COPD. No difference was found in autoantibody levels between patients with CF versus ILD. In sera taken post-LTx we found the same difference in anti-ET_AR and anti-AT₁R autoantibody titers between patients with CF versus COPD. No difference was found in antibody titers between sera taken prior to or 6months after LTx. There was no association between autoantibody levels and other relevant demographic parameters, and we found no association between autoantibody titers and the development of the bronchiolitis obliterans syndrome. Both autoantibody titers were strongly correlated. We hypothesize that due to prolonged exposure to bacterial infection, increased levels of AT₁R and ET_AR result in a deregulated immune response causing autoantibody formation. Further research is expedient to elucidate the occurrence of autoantibodies against ET_AR and AT₁R and their role in disease progression.