Investigation of non-human leukocyte antigen antibodies and epitope mismatch in kidney transplant recipients with chronic antibody-mediated rejection

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Background: There is a strong correlation between chronic antibody-mediated rejection (CAMR) and human leukocyte antigen (HLA) donor-specific antibodies (DSA) in kidney transplantation. However, cases of CAMR in kidney transplant recipients have been observed without DSA, suggesting the involvement of non-HLA antibodies. Some non-HLA antibodies have been reported to be associated with the histology of CAMR, but their specific contribution to rejection reactions remains unclear. In this study, we conducted a retrospective analysis to identify which antibodies are involved in the histological manifestation of CAMR cases where DSA was not detected after kidney transplantation. Methods: This study included 47 cases of CAMR identified among 868 kidney transplant cases performed at the Tokyo Women's Medical University Urology Department from 2015 to 2021. Out of these 47 cases, 38 were eligible for analysis, and among them, 13 cases were selected where DSA was not detected. The method involved analyzing serum samples obtained on the same day as kidney allograft biopsy. The samples were used to investigate the correlation between CAMR and HLA as well as non-HLA antibodies, and the HLA epitopes (HLA-Ep) between the donor and recipient. Results: Among the 13 cases, six cases showed the presence of HLA-Ep associated with DSA. Specifically, AT1R-Ab was detected in two cases, MICA-Ab in two cases, and PRKCH in one case. In two cases, no antibodies were detected. These findings suggest the necessity to investigate non-HLA antibodies when CAMR is observed. Conclusions: For cases with suspected rejection but no detection of DSA, screening for non-HLA antibodies may be helpful as an aid in effective rejection response treatment.

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