Autoantibodies directed against the angiotensin II type 1 receptor and the endothelin-1 type A receptor in patients with systemic sclerosis

Objectives To evaluate the clinical applicability of autoantibodies (AAbs) measured by ELISA against the angiotensin II type 1 receptor (AT₁ R) and endothelin-1 type A receptor (ET_A R) in systemic sclerosis (SSc) patients. Methods Serum samples from n=279 SSc patients from the Leiden Systemic Sclerosis cohort, n=42 patients with primary Raynaud’s phenomenon, n=24 patients with rheumatoid arthritis and n=20 healthy controls were tested for anti-AT₁ R- and anti-ET_A R AAbs. Levels were compared between groups with Mann-Whitney U tests or Kruskal-Wallis tests. Risk ratios and Kaplan-Meier analyses were used to determine associations between AAbs and disease manifestations or all-cause mortality. Analyses were repeated in an independent cohort with n=310 SSc patients from the Radboud University Medical Center. Results AAbs against AT₁ R and ET_A R could be detected by ELISA in the sera of all groups tested. Levels were slightly higher in the SSc group compared with the pooled non-SSc group (p=0.043). No associations could be found between anti-AT₁ R AAbs or anti-ET_A R AAbs and disease manifestations or all-cause mortality. In the Radboud cohort, patients with diffuse cutaneous SSc (p=0.001) and interstitial lung disease (p=0.007) had higher median anti-ET_A R AAb levels. Patients who died during follow-up had lower levels of anti-AT₁ R- (p=0.005) and anti-ET_A R AAbs (p=0.020). Conclusions We confirm positive ELISAs for anti-AT₁ R AAbs and anti-ET_A R AAbs in the sera of several patient groups and healthy controls. Previously described associations with disease manifestations and all-cause mortality could not be confirmed in our cohorts. Based on the current study, the determination of these AAbs is of limited predictive value in clinical practice.