This study was undertaken with the primary aim of analyzing the clinical relevance of posttransplant appearance of anti-human leukocyte antigen (HLA) and major histocompatibility (MHC) class I related chain A (MICA) antibodies in response to live related donor (LRD) renal transplantation. A total of 185 consecutive post renal transplant recipient serum samples were analyzed for the detection of anti-HLA by enzyme-linked immunoabsorbent assay (ELISA) and MICA antibodies using Luminex techniques. Patients with IgG HLA class I antibodies had more acute rejection episodes compared to the negative group (67% vs. 20%, chi(2) = 7.95, p = 0.005) and also had poor graft survival (44% vs 86%, chi(2) = 6.67, p = 0.01). Similarly, patients with anti-HLA class II antibodies also had significantly lower graft survival and a higher number of rejection episodes as compared to the antibody negative group (p = 0.002 and p = 0.000, respectively). Following transplantation, 30 patients (16%) developed antibodies against any of the MICA alleles (MICA001, MICA002, MICA004, MICA008, or MIC*009). The graft survival was significantly compromised in these patients as compared to the negative group (60% vs 86%, chi(2) = 10.26, p = 0.001). Further, patients carrying both antibodies (MICA+/HLA+) were the worst affected and showed significantly poor graft survival as compared to the MICA-/HLA- group (17% vs 89%, chi(2) = 19.63, p = 0.000). Similarly, patients with only MICA antibodies or those with only HLA antibodies also had significantly lower graft survival and a higher number of acute rejection episodes (p = 0.035 and p = 0.001, respectively) as compared to the nonsensitized group. The study illustrates that posttransplant monitoring of antibodies to both MICA as well as HLA could be an important prognostic marker in renal transplant subjects.