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The pathogenesis of transplant glomerulopathy (TG) remains unclear, with evidence of human leukocyte antigen (HLA) antibodies as important contributors to the disease. We studied the risk factors and the associations of HLA antibodies in the development of TG. Sixty-one cases with morphologic features of TG were identified and compared with contemporaneous matched patients (without TG) from a 17-year period, all undergoing renal biopsy in a single center. Univariate risk factors for TG were previous glomerulitis [odds ratio (OR) 3.3, 95% confidence interval (95% CI) [1.2-9.4], p = 0.025), delayed graft function (OR 2.3 [1.0-5.1], p = 0.042), HLA class I presensitization defined by Luminex solid-phase immunoassays (OR 5.0 [2.3-11.0]. p0.001), and de novo posttransplant development of donor HLA specific antibody (DSA) (OR 4.7 [1.7-13.2], p = 0.002). Only DSA remained significantly associated with TG after adjustment (OR 3.8 [1.1-12.9], p = 0.032). DSA was detected in50% of TG patients, suggesting HLA antibodies play a critical role in TG pathogenesis. TG patients with DSA had increased risk of graft loss (median graft survival 4.4-5.2 years), whereas patients with morphologic features of TG without DSA had similar graft survival compared with the non-TG group (median graft survival 15 years). Thus, DSA is a useful predictor for graft failure in TG patients.

B-cell crossmatch (BXM) was originally introduced to increase the sensitivity to detect anti-HLA antibodies of conventional CDC crossmatch in renal transplantation. Newer techniques such as Luminex((R)) have greater sensitivity in detecting anti-HLA antibodies but have not been directly evaluated versus BXM. We discuss our experience with Luminex testing and the significance of donor-specific antibodies (DSA) defined by Luminex in three populations, as compared with the CDC crossmatch. In the general transplant population, Luminex-defined DSA were found in only one third of positive CDC-BXM and were associated with graft rejection. Luminex testing enhanced the interpretation of CDC-BXM and identified patients with clinically relevant BXM. In the highly sensitized transplant population, Luminex-defined DSA were found in two thirds of positive BXM and were a better predictor of graft rejection. Therefore, Luminex assays rather than CDC-BXM should be used to facilitate kidney allocation in highly sensitized patients. In the post-transplantation population, Luminex antibody monitoring for DSA was shown to be important, as it defined low-level de novo DSA that were associated with development of transplant glomerulopathy and a significant predictor of graft loss in those patients. Thus Luminex testing facilitated the interpretation of CDC-BXM and provided a useful predictive tool for the detection of clinically significant DSA in post-transplantation antibody monitoring.