On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomes
Meneghini, Maria (Hospital Universitari Vall d'Hebron)
Perona, Anna (Universitat de Barcelona)
Crespo, Elena (Vall d'Hebron Institut de Recerca (VHIR))
Bemelman, Frederike (Amsterdam University Medical Center (UMC))
Reinke, Petra (Berlin Center for Advanced Therapies)
Viklicky, Ondrej (Institute for Clinical and Experimental Medicine)
Giral, Magali (Nantes Université)
Palou, Eduard (Hospital Clínic i Provincial de Barcelona)
Torija, Alba (Vall d'Hebron Institut de Recerca (VHIR))
Donadeu, Laura (Vall d'Hebron Institut de Recerca (VHIR))
Melilli, Edoardo (Hospital Universitari de Bellvitge)
Zúñiga, José Miguel (Vall d'Hebron Institut de Recerca (VHIR))
Sefrin, Anett (Berlin Center for Advanced Therapies)
Lachmann, Nils (Charité-Universitätsmedizin Berlin)
Hu, Liu (Amsterdam University Medical Center (UMC))
Hruba, Petra (Institute for Clinical and Experimental Medicine)
Guillot-Gueguen, Cécile (Nantes Université)
Brouard, Sophie (Nantes Université)
Grinyo, Josep (Universitat de Barcelona)
Bestard Matamoros, Oriol (Vall d'Hebron Institut de Recerca (VHIR))
Universitat Autònoma de Barcelona

Data:	2022
Resum:	Complete and high-resolution (HR) HLA typing improves the accurate assessment of donor-recipient compatibility and pre-transplant donor-specific antibodies (DSA). However, the value of this information to identify de novo immune-mediated graft events and its impact on outcomes has not been assessed. In 241 donor/recipient kidney transplant pairs, DNA samples were re-evaluated for six-locus (A/B/C/DRB1/DQB1+A1/DPB1) HR HLA typing. De novo anti-HLA antibodies were assessed using solid-phase assays, and dnDSA were classified either (1) as per current clinical practice according to three-locus (A/B/DRB1) low-resolution (LR) typing, estimating donor HLA-C/DQ typing with frequency tables, or (2) according to complete six-locus HR typing. The impact on graft outcomes was compared between groups. According to LR HLA typing, 36 (15%) patients developed dnDSA (LR_dnDSA+). Twenty-nine out of 36 (80%) were confirmed to have dnDSA by HR typing (LR_dnDSA+/HR_dnDSA+), whereas 7 (20%) did not (LR_dnDSA+/HR_dnDSA-). Out of 49 LR_dnDSA specificities, 34 (69%) were confirmed by HR typing whereas 15 (31%) LR specificities were not confirmed. LR_dnDSA+/HR_dnDSA+ patients were at higher risk of ABMR as compared to dnDSA- and LR_dnDSA+/HR_dnDSA- (logRank < 0. 001), and higher risk of death-censored graft loss (logRank = 0. 001). Both LR_dnDSA+ (HR: 3. 51, 95% CI = 1. 25-9. 85) and LR_dnDSA+/HR_dnDSA+ (HR: 4. 09, 95% CI = 1. 45-11. 54), but not LR_dnDSA+/HR_dnDSA- independently predicted graft loss. The implementation of HR HLA typing improves the characterization of biologically relevant de novo anti-HLA DSA and discriminates patients with poorer graft outcomes.
Ajuts:	Ministerio de Economía y Competitividad ICI14/00242 Ministerio de Economía y Competitividad PI16/01321 Instituto de Salud Carlos III PI19/01710
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Allograft rejection ; Donor-specific antibodies ; HLA typing ; Kidney transplantation ; Precision medicine
Publicat a:	Frontiers in immunology, Vol. 13 (september 2022) , ISSN 1664-3224

DOI: 10.3389/fimmu.2022.924825
PMID: 36248818

12 p, 1.3 MB

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