C4D deposition and positive posttransplant crossmatch are not necessarily markers of antibody-mediated rejection in renal allograft recipients

The aim of the study was to search for serologic, immunopathologic, and morphologic evidence of antibody-mediated rejection (AMR) among patients with acute renal allograft dysfunction. The study included 19 patients with episodes of acute rejection (ARE) within the first year after transplantation. All patients had negative crossmatch tests before transplantation. Patients underwent biopsy for histologic and C4d examinations. All patients were monitored for donor-specific HLA alloantibodies during the first posttransplant year. Complement-dependent cytotoxic crossmatches were performed with donor lymphocytes. In eight patients, the crossmatch test results changed to positive during ARE. In all biopsies except one with cortical infarction, we observed C4d staining (group 1). The biopsies of four patients showed histologic changes of AMR, and all of their grafts were lost. In one patient, cellular and vascular rejection (Banff II) were present; in two, Banff I; and in one, borderline lesions. These results were compared with 11 patients with ARE but negative posttransplant crossmatches and negative staining for C4d (group 2). The histologic findings in the biopsies of these patients were cellular interstitial and vascular rejection (Banff I and Banff II). With no features suggestive of AMR. During the first year after transplantation, the creatinine levels of group 1 patients, were significantly higher than group 2 patients. One-year graft survival was 50% in group 1 and 91% in group 2. CONCLUSIONS: C4d and a positive posttransplant crossmatch were not associated with histologic features of AMR in half of the ARE. Nevertheless, C4d deposition and positive posttransplant crossmatches correlated with allograft injury among renal transplant patients.