Class II HLA eplet mismatch is related to anti-donor CD4+ T cell response and de novo donor-specific antibody development in kidney transplantation recipient
Hiroaki Yamane1, Yuka Tanaka1, Masahiro Ohira1, Hiroyuki Tahara1, Kentaro Ide1, Hideki Ohdan1.
1Gastroenterological Transplant Surgery, Hiroshima University, Hiroshima, Japan
Purpose: De novo donor-specific antigen (dnDSA) was associated with a long-term prognosis of kidney transplant recipient. Recently, HLA compatibility between a solid organ transplant recipient and donor is being defined at the epitope level thereby providing greater structural discernment than has historically been provided at the allelic level. We investigated (1) the correlation between HLA eplet mismatches and immune status and (2) between HLA eplets mismatches and dnDSA in kidney transplant recipients.
Method: We conducted a retrospective study of 88 living kidney recipients between 2011 and 2018. The HLA Matchmaker software package (version 2.1) was used to characterize epitope mismatches. And, we investigated the association between anti-donor T cell response using CFSE-MLR assay and eplet mismatches.
Result: The recipient’s median age was 49.5 years (18-73 year), 54 recipients were males and 34 recipients were females. (1) HLA I eplet mismatches were not associated with CD4 and CD8 stimulation index (SI). After 1 years, HLA II eplet mismatches and DRB1 eplet mismatches were significantly associated with CD4 SI (p=0.0092, 0.0074). Moreover, HLA DRB1 epletmismathes after 2 year were associated with CD4 SI (p=0.0414). (2) The number of eplet mismatches were compared between those with (n=13) and without (n=75) de novo DSA. The blood relationship and ABO blood type incompatibility were no significant difference between the groups with and without dnDSA. Class HLA I eplet mismatches was no significant difference (p=0.6166). On the other hand, Class HLA II eplet mismatches were significantly associated with dnDSA development (p=0.0453).
Conclusion: On long-term observation, more number of HLA II eplet mismatches might be affected immune status of transplant recipients. HLA II eplet mismatch is a risk factor for dnDSA in kidney transplantation recipients.
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