title: Refinement of the definition of permissible HLA-DPB1 mismatches with predicted indirectly recognizable HLA-DPB1 epitopes.
abstract: Hematopoietic stem cell transplantation with HLA-DPB1-mismatched donors leads to an increased risk of acute graft-versus-host disease (GVHD). Studies have indicated a prognostic value for classifying HLA-DPB1 mismatches based on T cell-epitope (TCE) groups. The aim of this study was to determine the contribution of indirect recognition of HLA-DP-derived epitopes, as determined with the Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) method. We therefore conducted a retrospective single-center analysis on 80 patients transplanted with a 10/10 matched unrelated donor that was HLA-DPB1 mismatched. HLA-DPB1 mismatches that were classified as GVH nonpermissive by the TCE algorithm correlated to higher numbers of HLA class I as well as HLA class II presented PIRCHE (PIRCHE-I and -II) compared with permissive or host-versus-graft nonpermissive mismatches. Patients with acute GVHD grades II to IV presented significantly higher numbers of PIRCHE-I compared with patients without acute GVHD (P < .05). Patients were divided into 2 groups based on the presence or absence of PIRCHE. Patients with PIRCHE-I or -II have an increased hazard of acute GVHD when compared with patients without PIRCHE-I or -II (hazard ratio [HR], 3.19; 95% confidence interval [CI], 1.10 to 9.19; P < .05; and HR, 4.07; 95% CI, .97 to 17.19; P = .06, respectively). Patients classified as having an HLA-DPB1 permissive mismatch by the TCE model had an increased risk of acute GVHD when comparing presence of PIRCHE-I with absence of PIRCHE-I (HR, 2.96; 95% CI, .84 to 10.39; P = .09). We therefore conclude that the data presented in this study describe an attractive and feasible possibility to better select permissible HLA-DPB1 mismatches by including both a direct and an indirect recognition model.
authors: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Kirsten A
authors: KA
authors: Thus
authors: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Mieke T A
authors: MT
authors: Ruizendaal
authors: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Talitha A
authors: TA
authors: de Hoop
authors: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Eric
authors: E
authors: Borst
authors: Department of Theoretical Biology & Bioinformatics, University Utrecht, Utrecht, the Netherlands.
authors: Hanneke W M
authors: HW
authors: van Deutekom
authors: Department of Hematology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Liane
authors: L
authors: Te Boome
authors: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Hematology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Jürgen
authors: J
authors: Kuball
authors: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: e.spierings@umcutrecht.nl.
authors: Eric
authors: E
authors: Spierings
mesh_terms: D000328:Adult; D015331:Cohort Studies; D000939:Epitopes / Q000276:immunology*; D005260:Female; D059868:HLA-DP beta-Chains / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D019172:Transplantation Conditioning / Q000379:methods*; D061349:Unrelated Donors
chemical_list: D000939:Epitopes; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen
keywords: Acute graft-versus-host disease; HLA-DP; Hematopoietic stem cell transplantation; Indirect recognition; Mismatch; PIRCHE