The detection and characterization of anti-HLA antibodies and the clinical impact of their appearance following renal transplantation are areas of immense interest. In particular, de novo development of donor-specific antibodies (DSA) has been associated with acute and chronic antibody-mediated graft rejection (AMR). Recently, methods for antibody detection have evolved remarkably from conventional cell-based assays to advanced solid phase systems. These systems have revolutionized the art of defining clinically relevant antibodies that are directed toward a renal graft. While anti-HLA DSAs have been widely associated with poor graft survival, the role of non-HLA antibodies, particularly those directed against endothelial cells, is beginning to be realized. Appreciation of the mechanisms underlying T cell recognition of alloantigens has generated great interest in the use of synthetic peptides to prevent graft rejection. Hopefully, continued progress in unraveling the molecular mechanisms of graft rejection and posttransplant monitoring of antibodies using highly sensitive testing systems will prove beneficial to immunological risk assessment and early prediction of renal allograft failure.
Besides the overriding influence of anti-HLA antibodies on the overall graft survival, immune response to non-HLA antigens has become a subject of substantial interest in recent years. The much-needed impetus towards understanding the relevance of non-HLA antibodies has come from multicentric analysis involving a large cohort of renal allograft recipients and published under the aegis of the Collaborative Transplant Study (CTS). 1 Subsequently, several investigators have highlighted an important role of non-HLA antibodies not only in kidney transplants, but also in those involving other organs such as heart and lung. 2-7 Major histocompatibility complex class I chain-related molecule A (MICA), the most notable
Not all anti‐HLA donor‐specific antibodies (HLA‐DSAs) are detrimental to renal allograft. In this context, the C1q complement activating ability of antibodies appears to be an important parameter to distinguish clinically inert versus detrimental DSAs. We evaluated sera of 206 consecutive primary live donor renal transplant recipients before transplant and at post‐operative day 7, 30, 90, 180 and at the time of graft dysfunction for quantifying HLA‐DSAs using single antigen bead assay on a Luminex platform. Patients positive for these antibodies with an MFI >500 were further screened for C1q fixing nature of DSA. Fourteen of the 18 antibody‐positive patients had C1q fixing DSA with MFI value >5000. Only 4 antibody‐positive patients did not have C1q fixing DSA. The MFI values of DSA detected by C1q assay were generally higher at least by 25% than those detected by the conventional IgG‐SAB assay. Twelve of the 14 patients (85.71%) with C1q+ DSA developed antibody‐mediated rejection during the mean follow‐up period of 21.43 ± 8.03 months as compared to none of the four C1q‐negative DSA (85.71% vs 0%; P = .001). These results suggest deleterious effect of C1q+ DSA vis‐à‐vis C1q‐negative DSA on renal allograft.
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