Aab targeting GPCRs have been characterized in several rheumatic diseases. In particular, anti-GPCR aab have been deeply investigated in patients with Systemic sclerosis (SSc), which is an autoimmune disease mainly characterized features by the development of autoimmunity, vasculopathy and tissue fibrosis. The renin-angiotensin and endothelin systems have been implicated in vasculopathy and fibrosis. Riemenkasten et al. identified the association of anti- AT1R and anti-ETAR aab with clinical symptoms of SSc (32). They investigated serum samples from SSc patients from three independent cohorts (n=478) and compared them with healthy controls (n=372) and control diseases (n=311). Antibodies against AT1R and ETAR were elevated in patients suffering from SSc. Higher levels of anti-AT1R and anti-ETAR aab were associated with different severe disease manifestations and predicted SSc-related mortality. Anti-AT1R and anti-ETAR aab contribute to disease pathogenesis and therefore they should be used as biomarkers for the risk assessment of disease progression.

Avouac et al. showed that in patients with SSc (n=90) anti-ETAR aab are strong predictors for digital ulcers in a five year follow-up (43).

In addition, Becker et al. investigated patients with SSc related pulmonary arterial hypertension (PAH, n=81) and connective tissue disease-associated PAH (n=110) compared with other forms of pulmonary hypertension (n=106), (44). The predicted outcomes for PAH, associated with SSc, was worse than for the other forms of PAH. Anti-AT1R and anti-ETAR aab are more frequent in SSc related PAH and in connective tissue disease related PAH compared to other forms of pulmonary hypertension. Anti-AT1R and anti-ETAR aab serve as predictors and prognostic biomarkers in SSc related PAH.

Kill postulates that Angiotensin and endothelin-receptor activation via anti-AT1R and anti- ETARaab mediate pathogenic effects, indicating their contribution to pathogenesis of SSc (45, 46).


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  4. A Kill, C Tabeling, R Undeutsch, AA Kühl, J Günther, M Radic, MO Becker, H Heidecke, M Worm, M Witzenrath, GR Burmester, D Dragun, G Riemekasten. Autoantibodies to angiotensin and endothelin receptors in systemic sclerosis induce cellular and systemic events associated with disease pathogenesis. Arthritis Res Ther. 16(1), R29 (2014)
  5. J Günther, A Kill, MO Becker, H Heidecke, J Rademacher, E Siegert, M Radić, GR Burmester, D Dragun, G Riemekasten. An­giotensin receptor type 1 and endothelin receptor type A on immune cells mediate migration and the expression of IL-8 and CCL18 when stimulated by autoantibodies from systemic sclerosis patients. Arthritis Res Ther. 16(2), R65 (2014)