Antibodies against AT1-receptor in transplantation (diagnostics, treatment, clinical relevance)

The influence of ATR-1-autoantibodies on antibody mediated rejection (AMR) is still discussed controversially. Here we demonstrate some aspects as to diagnostics, treatment, clinical relevance and graft outcome.

A total of 27 transplant recipients (6 heart, 16 kidney, 3 lung and 2 multi-organ) suffering from AMR and a control group without transplant (8 pre-Tx, 1 pregnancy and 16 autoimmune and haematological diseases) were studied. In total, 290 IA eluates and the corresponding patient serum samples before and after immunoadsorption (IA) were analysed.

ATR-1-and ETR-auto-antibodies (aAB) were found only in 4.5% of sera previous to IA treatment by using ELISA, but could be detected in 42% of IA eluates. AB with very high titres (>1:8 to 1:256) in the eluate were found more frequently in heart than in kidney recipients. These strong aAB are clinically relevant and cause dysfunction or loss of the grafts. A quick and reliable diagnosis of the aAB is essential for successful application of the therapeutic possibilities, like removal of the pathogenic autoantibodies or the blockage of their actions.

The use of eluates for antibody detection was more sensitive and more reliable than patient serum. Yet, the test results are only meaningful when AB titres are measured, as this allows for a quick statement about the actual antibody elimination. The removal of pathogenic aAB via IA is better than medication-based treatment.