The renin-angiotensin system (RAS) or the renin-angiotensin-aldosterone system (RAAS) is a hormone system that regulates blood pressure and water (fluid) balance. If the renin-angiotensin-aldosterone system is too active, the blood pressure becomes too high. The auto-immune activation of the immunsystem is mediated by the production of auto-antibodies.
Angiotensin Type 1 Receptor (AT1R) mediates most physiologic and pathophysiologic actions of its endogenous ligand: angiotensin II. Overactivity leads to vascular remodeling and hypertension. Autoantibodies to AT1R are associated with severe vascular rejection in scleroderma and in neurological diseases.
Prof. D. Dragun et al. have reported the presence of antibodies against AT1R in 16 renal allograft recipients who had severe vascular rejection and malignant hypertension but no donor HLA specific antibodies (HLA-DSA). New England Journal of Medicine (2005), 352, 558-569
Prof. N. Reinsmoen, Cedars-Sinai Medical Center, Los Angeles, and Prof. D. Dragun, Charite Medical School, Berlin, investigated the impact of the antibody to AT1R on clinical outcomes including antibody mediated rejection (AMR), with or without C4d deposition, in patients whose sera contained no donor human leukocyte antigen (HLA)-specific antibody (HLA-DSA).
A strong association was observed between the high binding affinity of the AT1R antibodies to AT1R and AMR in recipients whose sera contained no antibody to donor HLA or MICA. Assessing the AT1R antibody status along with the HLA-DSA provides additional information to determine the immunologic risk for recipients. Transplantation (2010), 90, 1473-1477
PD Dr. M. Barten and Prof. F. Mohr, Heart Center Leipzig, and Prof. D. Dragun, Charite Medical School, Berlin, showed that early and higher incidence of cardiac allograft vasculopathy (CAV) after heart transplantation is linked to angiotensin-receptor-I auto antibodies and endothelin-receptor-A auto antibodies. These results point out the necessity of monitoring HLA and non-HLA antibodies after HTx.
Prof. G. Riemekasten and Prof. D. Dragun, Charite Medical School, Berlin, investigated the involvement of the antibody to AT1R and ETAR in systemic sclerosis. Functional autoimmunity directed at AT1R and ETAR is common with SSc. AT1R and ETAR autoantibodies could contribute to disease pathogenesis and serve as biomarkers for risk assesment of disease progression.