The effect of MICA antigens on transplant outcomes: A systematic review

Background and Objective: Human major histocompatibility complex class I-related gene A (MICA) is reportedly associated with poor transplant outcomes and a high risk of acute and chronic rejection in solid organ transplantation. However, studies on these risks have found conflicting results. In order to identify areas in which additional research is needed, we have undertaken the first systematic review of evidence concerning the risk of anti-MICA antibodies in recipients’ sera. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library for original reports of clinical studies involving detection of MICA abs in transplant recipients’ sera which used survival rate, acute rejection, and/or chronic rejection as outcome measures. RevMan 5.0.15 was used to calculate relative risk (RR), odds ratios (ORs), and 95% confidence intervals (95%CIs). Results: We found 18 relevant articles, with a total of 6,607 recipients. Follow-up duration ranged from 1 to 15 years. In studies with more than 2 years of follow-up, anti-MICA abs positive in kidney recipients’ post-transplant sera was associated with a lower graft survival rate (4 years: RR = 2.04, 95%CI 1.30 to 3.22; 3 years: OR = 3.56, 95%CI 1.47 to 8.62; 2 years: RR = 2.17, 95%CI 1.09 to 4.31) and a higher acute rejection rate (RR = 1.92, 95%CI 1.27 to 2.91), but there was no clear association with chronic rejection. Similar conclusions could not be drawn for heart or liver transplantation due to possible confounding by anti-HLA abs and the small sample sizes of the available studies. Conclusion: Anti-MICA antibodies in recipients’ sera may associated with poor graft survival rates and high risk of acute and chronic rejection in solid organ transplantation, but more rigorous studies are needed to confirm or refute this relationship. Current immunosuppressive therapy may fail to suppress the harmful effect of MICA antigens.