A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive mismatches for hematologic stem cell transplantation
From the HLA Tissue Typing Laboratory, Immunohematology and Transfusion Medicine Service, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Hematology and Bone Marrow Transplantation Unit, Cancer Immunotherapy and Gene Therapy Program, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Scientifico H. S. Raffaele, Milan, Italy; Immunogenetics Laboratory, Unit of Clinical Epidemiology and Trials, IRCCS National Institute for Cancer Research, Genoa, Italy; Department of Hematology, Imperial College, London, United Kingdom; HLA Tissue Typing Laboratory, Immunohematology and Transfusion Medicine Service, Department of Pediatric Hematology-Oncology, IRCCS Policlinico S. Matteo, Pavia, Italy; HLA Tissue Typing Laboratory, Immunohematology and Transfusion Medicine Service, Institute of Hematology and Medical Oncology, University of Bologna, Ospedale S. Orsola-Malpighi, Bologna, Italy; Department of Pediatric Hematology-Oncology, IRCCS G. Gaslini, Genoa, Italy; Department of Hematology, Ospedale San Martino, Genoa, Italy; and Department of Oncology, Biology and Genetics, University of Genoa, Genoa, Italy.v.*x|0, 百拇医药
The importance of HLA-DPB1 matching for the outcome of allogeneic hematologic stem cell (HSC) transplantation is controversial. We have previously identified HLA-DPB1*0901 as a target of cytotoxic T cells mediating in vivo rejection of an HSC allograft. Here we show that HLA-DPB1*0901 encodes a T-cell epitope shared by a subset of DPB1 alleles that determines nonpermissive mismatches for HSC transplantation. Several T-cell clones obtained from the patient at the time of rejection showed HLA-DP restricted recognition of allogeneic targets expressing HLA-DPB1*0901, *1001, *1701, *0301, *1401, and *4501, but not other alleles. Based on these findings, we developed an algorithm for prediction of nonpermissive HLA-DPB1 mismatches. Retrospective evaluation of 118 transplantations showed that the presence of nonpermissive HLA-DPB1 mismatches was correlated with significantly increased hazards of acute grade II to IV graft-versus-host disease (HR = 1.87, P = .046) and transplantation-related mortality (HR = 2.69, P = .027) but not relapse (HR = 0.98, P = .939), as compared with the permissive group. There was also a marked but statistically not significant increase in the hazards of overall mortality (HR = 1.64, P = .1). These data suggest that biologic characterization of in vivo alloreactivity can be a tool for definition of clinically relevant nonpermissive HLA mismatches for unrelated HSC transplantation.(Elisabetta Zino Guido Frumento Sarah Marktel Maria Pia Sormani Francesca Ficara Simona Di Terlizzi A)
The importance of HLA-DPB1 matching for the outcome of allogeneic hematologic stem cell (HSC) transplantation is controversial. We have previously identified HLA-DPB1*0901 as a target of cytotoxic T cells mediating in vivo rejection of an HSC allograft. Here we show that HLA-DPB1*0901 encodes a T-cell epitope shared by a subset of DPB1 alleles that determines nonpermissive mismatches for HSC transplantation. Several T-cell clones obtained from the patient at the time of rejection showed HLA-DP restricted recognition of allogeneic targets expressing HLA-DPB1*0901, *1001, *1701, *0301, *1401, and *4501, but not other alleles. Based on these findings, we developed an algorithm for prediction of nonpermissive HLA-DPB1 mismatches. Retrospective evaluation of 118 transplantations showed that the presence of nonpermissive HLA-DPB1 mismatches was correlated with significantly increased hazards of acute grade II to IV graft-versus-host disease (HR = 1.87, P = .046) and transplantation-related mortality (HR = 2.69, P = .027) but not relapse (HR = 0.98, P = .939), as compared with the permissive group. There was also a marked but statistically not significant increase in the hazards of overall mortality (HR = 1.64, P = .1). These data suggest that biologic characterization of in vivo alloreactivity can be a tool for definition of clinically relevant nonpermissive HLA mismatches for unrelated HSC transplantation.(Elisabetta Zino Guido Frumento Sarah Marktel Maria Pia Sormani Francesca Ficara Simona Di Terlizzi A)