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In order to look for a relationship between humoral mechanisms of rejection and chronic allograft dysfunction, plasma cells, C4d deposits and donor-specific antibodies (DSA) were simultaneously sought on serial biopsies of kidney allograft recipients.Ten recipients with chronic dysfunction (G1) and 8 recipients with long-term normal graft function (G2) were included. Biopsies and serums were sampled at early graft dysfunction (T1), between 8months and 2years (T2) and after the third year following transplantation (T3).In G1, plasma cells represented 12.3% (T1), 8.2% (T2) and 14.1% (T3) of mononuclear cells. The mean percentage of plasma cells was 11.6% in G1 versus 0.4% in G2 (p0.05). A progressive rise in C4d deposits was seen in G1, from 25% at T1 to 80% at T3. Donor-specific antibodies were identified in at least one serum sample of 60% of the patients in G1 and 12.5% of the patients in G2 (p=0.012), whereas donor-specific antibodies were eluted from at least one biopsy of 50% of the patients in G1 and 12.5% of the patients in G2 (p=0.03). In G1, C4d deposits were significantly associated with plasma cells (p=0.0012) and anti-HLA Abs in serum samples and/or eluates (p=0.026).This study shows that plasma cells, DSA and C4d are associated in renal transplants developing chronic rejection.

Background Emerging data suggest that donor-specific HLA antibodies should be more frequently found onto the transplant itself than in the bloodstream. It is now possible to detect such antibodies in kidney transplant needle biopsy samples by flow cytometry. In order to know if the detection of antibodies into such blind biopsy samples depends of the site of the biopsy, we have studied the distribution of antibodies in both the cortex and medulla of 12 transplants removed after graft loss due to chronic allograft nephropathy, and in 10 controls. Methods Donor-specific HLA antibodies were extracted from the cortex and the medulla of each removed transplant by an acid elution and characterized by Luminex® assays. Results They were found in 58.3% of transplants with chronic allograft nephropathy and never in other kidney samples. The same antibodies were found in the bloodstream at the time of transplantectomy in only 16.6% of the recipients. The distribution between the cortex and medulla was concordant in 75% of cases. However, we observed 2 discrepancies: one in favor of the cortex and one in favor of the medulla. A majority (5/7) transplants with CAN and intra-graft donor-specific antibodies had also C4d deposits along peritubular capillaries. Conclusion Testing for donor-specific HLA antibodies in kidney transplant needle biopsies can be of value provided the biopsy includes both the cortex and the medulla.