title: DPB1 disparities contribute to severe GVHD and reduced patient survival after unrelated donor bone marrow transplantation.
abstract: In order to evaluate the impact of HLA-DBP1 incompatibilities on the occurrence of acute graft-versus-host disease (GVHD) in unrelated hematopoietic cell transplantation, we studied 57 donor/recipient pairs characterized by their allelic identity for HLA-A, B, C, DRB1 and DQB1 and also for DRB3, 4, 5 loci and aimed to correlate DPB1 mismatches to already described risk factors for GVHD using multivariate Cox regression analysis. DPB1 identity between donor and recipient was observed in 24% and DPB1 compatibility (GVHD vector) in 42%. Two factors were independently associated with severe acute GVHD: two DP incompatibilities (RR = 8.25, 95% confidence interval (CI): 1.67-40.10, P = 0.010) and disease risk (RR = 10.23, 95% CI: 1.12-93.13, P = 0.012). Two DPB1 incompatibilities appeared also to be a factor in poorer survival independent of its effect on acute GVHD (RR = 4.97, 95% Cl: 1.80-13.71, P = 0.002). A correlation between acute GVHD and matching for each individual DPB1 polymorphic region and for residue 69 of the DP beta molecule, which seems to be a key residue in the alloimmune response, was not observed. Our data indicate that the outcome of unrelated hematopoietic cell transplantation in terms of GVHD but also survival, could be improved through HLA-DPB1 matching or at least by avoiding two DPB1 mismatches.
authors.affiliation: Service d'Immunologie et d'Histocompatibilité, Hôpital Saint Louis-AP, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Loiseau
authors.forename: H
authors.initials: H
authors.lastname: Espérou
authors.forename: M
authors.initials: M
authors.lastname: Busson
authors.forename: R
authors.initials: R
authors.lastname: Sghiri
authors.forename: R
authors.initials: R
authors.lastname: Tamouza
authors.forename: M
authors.initials: M
authors.lastname: Hilarius
authors.forename: C
authors.initials: C
authors.lastname: Raffoux
authors.forename: A
authors.initials: A
authors.lastname: Devergie
authors.forename: P
authors.initials: P
authors.lastname: Ribaud
authors.forename: G
authors.initials: G
authors.lastname: Socié
authors.forename: E
authors.initials: E
authors.lastname: Gluckman
authors.forename: D
authors.initials: D
authors.lastname: Charron
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology* / Q000401:mortality; D006682:HLA-DP Antigens / Q000235:genetics / Q000276:immunology*; D059868:HLA-DP beta-Chains; D006648:Histocompatibility / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D015996:Survival Rate; D014019:Tissue Donors
chemical_list: D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen