Will MICA glitter for recipients of kidney transplants?

Renal transplantation as the treatment of choice for end-stage renal failure is associated with excellent short-term results. The 1-year patientsurvival rate is 96%, and the 1-year allograft-survival rate is more than 90%. Although the 5-year patient-survival rate after renal transplantation remains at about 90%, there is a steady attrition of allografts because of long-term rejection, which limits the 5-year allograft-survival rate to about 80%.1 In the more than half century since the first clinical renal transplantations in the early 1950s, the procedure has become standard practice. There has been steady progress in allograft survival since the development of proper HLA matching and sufficient immunosuppressive therapy.2 One or more mismatches in HLA-A, HLA-B, and HLA-DR antigens still reduce allograft survival significantly. A variety of “minor antigens,” a term that lumps together several diverse antigens besides the HLA antigens, also play a role in allograft failure, independent of HLA. Among such antigens, the ABO blood-group antigens are the most important, and generally the antigens in the transplanted kidney should match those in the recipient, as in red-cell transfusion3; this has led to longer waiting lists for prospective recipients of blood group O. ABO antigens are expressed on most cell membranes and in kidney tissue. These antigens occur in soluble form in plasma. The urea transporter expressing the Kidd blood-group antigens is another potential minor antigen.4 Since it was cloned in 1994,5 the protein expressing the major-histocompatibility-complex (MHC) class I–related chain A (MICA) antigens, which is structurally similar to MHC class I proteins, has become implicated in the slow process of longterm allograft failure.6,7 In this issue of the Journal, Zou and colleagues8 report the results of a retrospective study of MICA antigens in 1910 recipients of kidney transplants from deceased donors. MICA is a stress-inducible antigen expressed on the cell surface of epithelial and endothelial cells, fibroblasts, and monocytes. It is a ligand of the activating NKG2D receptor on natural killer cells, on γ/δ subgroups of T lymphocytes, and on α/β subgroups of CD8+ T lymphocytes. The diversity of protein variants encoded by the MICA gene9 may account for the fact that MICA, and not the closely related MHC class I–related chain B (MICB), is a good antigen to induce the humoral response. At the genetic level, MICA and MICB belong to the HLA class I gene complex, and they are located close to the HLA-B and HLA-A genes (Fig. 1). Anti-MICA antibodies were present in the pretransplantation serum samples of about 11% of the patients in the study by Zou et al. The mean (±SE) graft-survival rate at 1 year was poorer among patients with such antibodies (88.3±2.2%) as compared with the rate among patients without such antibodies (93.0±0.6%). This difference was still evident 5 years after transplantation. The risk associated with anti-MICA antibodies appeared to be highest among patients with wellmatched kidneys, which may hint that anti-MICA antibodies have an influence independent of HLA, and among patients with first renal transplants. HLA and clinical conditions other than immunization against MICA are more important than the presence of these antibodies, because no possible MICA effect was apparent in patients with HLA mismatches, retransplantation, or both. The results of the study by Zou et al. do not