Renal Transplantation

Abstract

It has been known for many years that patients with well-matched kidney transplants, even those who are matched at HLA-A, -B, and -DR, do not have indefinite allograft survival, and some kidneys fail as a result of rejection. In an attempt to understand the mechanism for rejection with graft loss in the face of excellent HLA matching, Zou et al. took pretransplantation sera from 1910 kidney transplant recipients and tested these sera for antibodies to MHC class I–related chain A (MICA) antigens. These antigens are expressed on the surface of epithelial cells, endothelial cells, fibroblasts, and monocytes. The MICA antigens are ligands of an activating receptor on natural killer cells and CD8+ T lymphocytes. Genes for these antigens are located close to the HLA-A and -B loci. ### Findings. Antibodies against these MICA antigens were detected in 11.4% of the 1910 patients. More important, the presence of these antibodies was associated with inferior graft survival compared with transplant centers without such antibodies (88 versus 93%; P = 0.01). In patients with good HLA matching (zero or one antigen mismatch of HLA-A plus HLA-B plus HLA-DR), sensitization to MICA was associated with even worse graft survival (83 versus 95% in individuals without such antibodies; P = 0.002). ### Commentary. This study provides a mechanism by which some allografts can be rejected, despite excellent matching and without anti-HLA antibodies. An editorial accompanying this article suggested that anti-MICA antibodies might be surrogate markers for a fundamental mechanism that mediates graft rejection, specifically, natural killer cell alloreactivity, which is due to these antigens’ binding to an activating ligand (1). It is possible that exploring this further may lead to better screening and cross-matching and further understanding of the role that these antigens may play in development of chronic allograft nephropathy.