title: Physiochemical disparity of mismatched HLA class I alloantigens and risk of acute GVHD following HSCT.
abstract: We determined whether assessment of the immunogenicity of individual donor-recipient HLA mismatches based on differences in their amino-acid sequence and physiochemical properties predicts clinical outcome following haematopoietic SCT (HSCT). We examined patients transplanted with 9/10 single HLA class I-mismatched grafts (n=171) and 10/10 HLA-A-, -B-, -C-, -DRB1- and -DQB1-matched grafts (n=168). A computer algorithm was used to determine the physiochemical disparity (electrostatic mismatch score (EMS) and hydrophobic mismatch score (HMS)) of mismatched HLA class I specificities in the graft-versus-host direction. Patients transplanted with HLA-mismatched grafts with high EMS/HMS had increased incidence of ⩾grade II acute GVHD (aGVHD) compared with patients transplanted with low EMS/HMS grafts; patients transplanted with low and medium EMS/HMS grafts had similar incidence of aGVHD to patients transplanted with 10/10 HLA-matched grafts. Mortality was higher following single HLA-mismatched HSCT but was not correlated with HLA physiochemical disparity. Assessment of donor-recipient HLA incompatibility based on physiochemical HLA disparity may enable better selection of HLA-mismatched donors in HSCT.
authors.affiliation: 1] Department of Surgery, University of Cambridge, and NIHR Cambridge Biomedical Research Centre, Cambridge, UK [2] Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: V
authors.initials: V
authors.lastname: Kosmoliaptsis
authors.affiliation: 1] Europdonor Foundation, Leiden, The Netherlands [2] Department of Immunohematology and Blood Transfusion, LUMC, Leiden, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: Jöris
authors.affiliation: Department of Surgery, University of Cambridge, and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
authors.forename: D H
authors.initials: DH
authors.lastname: Mallon
authors.affiliation: Department of Pediatrics, LUMC, Leiden, The Netherlands.
authors.forename: A C
authors.initials: AC
authors.lastname: Lankester
authors.affiliation: Department of Hematology, LUMC, Leiden, The Netherlands.
authors.forename: P A
authors.initials: PA
authors.lastname: von dem Borne
authors.affiliation: Department of Hematology and Immunology, UMCU, Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Kuball
authors.affiliation: Wilhelmina Children's Hospital, UMCU, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Bierings
authors.affiliation: Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Cornelissen
authors.affiliation: HOVON Data Centre, Erasmus MC Cancer Institute-Clinical Trial Center, Rotterdam, The Netherlands.
authors.forename: M E
authors.initials: ME
authors.lastname: Groenendijk-Sijnke
authors.affiliation: HOVON Data Centre, Erasmus MC Cancer Institute-Clinical Trial Center, Rotterdam, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: van der Holt
authors.affiliation: Department of Surgery, University of Cambridge, and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Bradley
authors.affiliation: 1] Europdonor Foundation, Leiden, The Netherlands [2] Department of Immunohematology and Blood Transfusion, LUMC, Leiden, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Oudshoorn
authors.affiliation: 1] Europdonor Foundation, Leiden, The Netherlands [2] Department of Immunohematology and Blood Transfusion, LUMC, Leiden, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: van Rood
authors.affiliation: Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Taylor
authors.affiliation: Department of Immunohematology and Blood Transfusion, LUMC, Leiden, The Netherlands.
authors.forename: F H J
authors.initials: FH
authors.lastname: Claas
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D064591:Allografts; D002648:Child; D016208:Databases, Factual; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000401:mortality; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015994:Incidence; D008297:Male; D009426:Netherlands; D012307:Risk Factors; D061349:Unrelated Donors
chemical_list: D006680:HLA Antigens