Polymorphism Of RAS In Patients With AT1-AA Mediated Steroid Refractory Acute Rejection

The steroid refractory acute rejection (SRAR) in renal transplantation is one of the major vital factors of the recipients. The main character of it is its acute course of disease with the low cure rate. The cause of the disease may be due to both of the immune mechanism and the nonimmune mechanism.Antibodies against HLA antigens cause refractory allograft rejection with vasculopathy in some, but not all, patients. Many aspects of T-cell-mediated responses in allograft rejection have been elucidated, yet humoral mechanisms are relatively unexplored. Vascular rejection that is refractory to intensified immunosuppression is the most important predictor of early and late graft loss. 1 The association of antidonor humoral reactivity against HLA antigens and vascular rejection has been established. Other targets of the allograft-directed host response remain elusive. However, alloantibodies against the polymorphic non-HLA system were found in serum obtained before transplantation from patients in whom refractory rejection developed after they received kidney transplants from HLA-identical siblings. Allograft endothelium may be a primary target of the cytopathic actions of non-HLA antibodies, triggering endothelial-cell activation or apoptosis. Identification of non-HLA antigens that are relevant to rejection might provide insight into underlying mechanisms, define risk-related phenotypes, and facilitate the development of specific therapies.We investigated the effects of gene polymorphisms of the four components of renin-angiotensin-aldosterone system (RAS) in renal transplant patients. Renal allograft recipients with SRAR had significantly higher frequencies of the DD genotype of ACE and CC genotype of AT1R than those without SRAR. The other genetic polymorphisms of the RAS were not associated with SRAR. Activating antibodies targeting the AT1 receptor were also detected in serum from all 14 SRAR victims with malignant hypertension and without anti-HLA antibodies, but in no other patients.The patients discussed here who were treated with losartan, protein A immunoabsorption, and intravenous immunoglobulin had amelioration of the antibody-mediated rejection process and remain free of rejection while receiving losartan. The treatment of removal these antibodies have been used in some desperate cases, with surprising success. However, their treatment was neither randomly assigned nor blinded, and the numbers of patients are too small to permit us to draw firm conclusions.This study proves that determination of polymorphism of the gene encoding components of RAS before transplantation may help identify patients who are at risk for SRAR. The detection of the antibodies of the HLA or AT1R may contribute to the prevention of SRAR. We speculate that detection of polymorphism of the gene encoding components of RAS and AT1-receptor antibodies in patients on a waiting list for a transplant might identify those at risk for refractory rejection.