TY - JOUR
T1 - HLA-DQ eplet mismatch load may identify kidney transplant patients eligible for tacrolimus withdrawal without donor-specific antibody formation after mesenchymal stromal cell therapy
AU - Bezstarosti, Suzanne
AU - Meziyerh, Soufian
AU - Reinders, Marlies E. J.
AU - Voogt-Bakker, Kim
AU - Groeneweg, Koen E.
AU - Roelen, Dave L.
AU - Kers, Jesper
AU - de Fijter, Johan W.
AU - Heidt, Sebastiaan
N1 - Funding Information: We thank the Jon J van Rood Transplantatiefonds (part of the LUMC Bontius Stichting) for funding the high-resolution HLA typing of the Triton patients and donors and we thank the HLA typing and screening laboratory Leiden, The Netherlands for technical assistance. Publisher Copyright: © 2023 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.
PY - 2023/7
Y1 - 2023/7
N2 - Recently, the randomized phase-II Triton study demonstrated that mesenchymal stromal cell (MSC) therapy facilitated early tacrolimus withdrawal in living donor kidney transplant recipients. The current sub-study analyzed formation of de novo donor-specific HLA antibodies (dnDSA) in the context of the degree of HLA eplet mismatches. At the time of protocol biopsy at 6 months, 7/29 patients (24%) in the MSC group and 1/27 patient (3.7%) in the control group had developed dnDSA. In the MSC group, all dnDSA were anti-HLA-DQ; two patients had anti-DQ alone and five patients combined with anti-class I, HLA-DR or -DP. Despite excess dnDSA formation in the MSC-arm of the study, the evolution of eGFR (CKD-EPI) and proteinuria were comparable 2 years posttransplant. All dnDSA were complement-binding and three patients had antibody-mediated rejection in the protocol biopsy, but overall rejection episodes were not increased. Everolimus had to be discontinued in nine patients because of toxicity, and tacrolimus was reintroduced in six patients because of dnDSA formation. The HLA-DQ eplet mismatch load independently associated with dnDSA (adjusted hazard ratio = 1.07 per eplet mismatch, p = 0.008). A threshold of ≥11 HLA-DQ eplet mismatches predicted subsequent dnDSA in all 11 patients in the MSC group, but specificity was low (44%). Further research is warranted to explore HLA molecular mismatch load as a biomarker to guide personalized maintenance immunosuppression in kidney transplantation.
AB - Recently, the randomized phase-II Triton study demonstrated that mesenchymal stromal cell (MSC) therapy facilitated early tacrolimus withdrawal in living donor kidney transplant recipients. The current sub-study analyzed formation of de novo donor-specific HLA antibodies (dnDSA) in the context of the degree of HLA eplet mismatches. At the time of protocol biopsy at 6 months, 7/29 patients (24%) in the MSC group and 1/27 patient (3.7%) in the control group had developed dnDSA. In the MSC group, all dnDSA were anti-HLA-DQ; two patients had anti-DQ alone and five patients combined with anti-class I, HLA-DR or -DP. Despite excess dnDSA formation in the MSC-arm of the study, the evolution of eGFR (CKD-EPI) and proteinuria were comparable 2 years posttransplant. All dnDSA were complement-binding and three patients had antibody-mediated rejection in the protocol biopsy, but overall rejection episodes were not increased. Everolimus had to be discontinued in nine patients because of toxicity, and tacrolimus was reintroduced in six patients because of dnDSA formation. The HLA-DQ eplet mismatch load independently associated with dnDSA (adjusted hazard ratio = 1.07 per eplet mismatch, p = 0.008). A threshold of ≥11 HLA-DQ eplet mismatches predicted subsequent dnDSA in all 11 patients in the MSC group, but specificity was low (44%). Further research is warranted to explore HLA molecular mismatch load as a biomarker to guide personalized maintenance immunosuppression in kidney transplantation.
KW - HLA
KW - HLA-DQ
KW - donor-specific antibodies
KW - eplet
KW - mesenchymal stromal cell
KW - tacrolimus
KW - transplantation
UR - http://www.scopus.com/inward/record.url?scp=85150236745&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/tan.15008
DO - https://doi.org/10.1111/tan.15008
M3 - Article
C2 - 36841928
SN - 2059-2302
VL - 102
SP - 3
EP - 12
JO - HLA
JF - HLA
IS - 1
ER -