Post transplant development of MICA and anti-HLA antibodies is associated with acute rejection episodes and renal allograft loss

Abstract

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 (MICA*001, MICA*002, MICA*004, MICA*008, 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.