Analysis of de novo donor‐specific HLA‐DPB1 antibodies in kidney transplantation

Abstract

HLA matching and avoidance of unacceptable mismatches are important aspects in the selection of donors for solid organ transplantation. The impact of HLA-DPB1 incompatibility on the outcomes of kidney transplantation is not fully understood. We investigated a potential effect of mismatching for HLA-DPB1 at allele, eplet, or Terasaki epitope (TerEp) level on the formation of de novo donor-specific antibodies (dnDSA) and also asked whether polymorphisms associated with HLA-DPB1 expression level may influence dnDSA induction. Furthermore, we analyzed the correlation between graft survival and HLA-DPB1 mismatches defined by different approaches.

HLA‐DPB1 molecular mismatches are risk factors for acute rejection and low 5‐year graft function in first kidney transplants

“…It is of note that EpMM, which are traditionally associated with antibodyrecognized epitopes, were associated with AR that essentially consisted of TCMR, as all the 19 cases of biopsy proven rejections were diagnosed as TCMR. This finding is consistent with the study by Tang et al, 2 which reported that HLA-DPB1 EpMM or TerEpMM impacted kidney graft survival but were not associated with the development of HLA-DPB1 DSA. On the other hand, the association of HLA-DPB1 expression and EpMM with HLA-DP DSA development was reported in solid organ transplantation, however the study did not report the type of organs included.…”

“…17 The present study did not detect any association of HLA-DPB1 allelic MM with AR or low 5Y-GF, in line with previous reports of lack of association between HLA-DP antigenic/allelic MM and survival of first kidney grafts. 1,2 All HLA-DPB1 mMM types, as well as higher levels of donor terminal Cr, were more frequent in cases with AR, in univariate analyses. The multivariate analyses were performed including donor terminal Cr and only one of the mMM types in each model, since all the polymorphisms in the HLA-DPB1 gene that determine the mMM are closely correlated.…”

“…HLA-DPB1 compatibility is not considered in any kidney allocation algorithm and this policy is based on a limited number of studies that did not identify any impact of HLA-DP mismatches (MM) on graft survival in first kidney transplant recipients. 1,2 In retransplants, on the other hand, HLA-DPB1 MM have been shown to be associated with lower graft survival. 1 Despite the lack of association between HLA-DPB1 MM and first kidney graft survival, HLA-DP donor specific antibodies (DSA) may be detected in first kidney graft recipients and there are suggestions that these antibodies may cause or contribute, along with other DSA, to rejection of first or repeat kidney grafts.…”

“…This study also included an investigation of HLA-DPB1 expression MM and no association was observed with any of the end-points. 2 While many studies have demonstrated the impact of HLA-DR and -DQ mMM on kidney transplant outcomes, [27][28][29][30][31][32] data on the role of HLA-DPB1 mMM are limited. Therefore, the present study aims to investigate a possible association between five different HLA-DPB1 mMM, that is, expression MM, 22 TCE MM, 19 EMM, 3 eplet MM (EpMM), 25 and solvent-accessible amino acid MM (SAMM), 33 and occurrence of acute rejection (AR) and low long-term graft function in a cohort of first kidney transplant recipients.…”

“…HLA‐DPB1 compatibility is not considered in any kidney allocation algorithm and this policy is based on a limited number of studies that did not identify any impact of HLA‐DP mismatches (MM) on graft survival in first kidney transplant recipients 1,2 . In retransplants, on the other hand, HLA‐DPB1 MM have been shown to be associated with lower graft survival 1 .…”