A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive mismatches for hematologic stem cell transplantation

被引:180
作者
Zino, E
Frumento, G
Marktel, S
Sormani, MP
Ficara, F
Di Terlizzi, S
Parodi, AM
Sergeant, R
Martinetti, M
Bontadini, A
Bonifazi, F
Lisini, D
Mazzi, B
Rossini, S
Servida, P
Ciceri, F
Bonini, C
Lanino, E
Bandini, G
Locatelli, F
Apperley, J
Bacigalupo, A
Ferrara, GB
Bordignon, C
Fleischhauer, K
机构
[1] Ist Sci San Raffaele, Tissue Typing Lab,Hematol & Bone Marrow Transplan, HLA,Immunohematol & Transfus Med Serv,IRCCS, San Raffaele Telethon Inst Gene Therapy,HSR,TIGET, I-20132 Milan, Italy
[2] Natl Inst Canc Res, IRCCS, Immunogenet Lab, Unit Clin Epidemiol & Trials, Genoa, Italy
[3] Univ London Imperial Coll Sci Technol & Med, Dept Hematol, London SW7 2AZ, England
[4] Policlin San Matteo, IRCCS, Dept Pediat Hematol Oncol, HLA Tissue Typing Lab,Immunohematol & Transfus Me, I-27100 Pavia, Italy
[5] Univ Bologna, Osped S Orsola Malpighi, HLA Tissue Typing Lab,Inst Hematol & Med Oncol, Immunohematol & Transfus Med Serv, I-40126 Bologna, Italy
[6] IRCCS G Gaslini, Dept Pediat Hematol Oncol, Genoa, Italy
[7] Osped San Martino Genova, Dept Hematol, Genoa, Italy
[8] Univ Genoa, Dept Oncol Biol & Genet, I-16126 Genoa, Italy
关键词
D O I
10.1182/blood-2003-04-1279
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页码:1417 / 1424
页数:8
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