title: Donor Cell Composition and Reactivity Predict Risk of Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.
abstract: Background. Graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). We designed a functional assay for assessment of individual risk for acute GVHD.Study Design and Methods. Blood samples were collected from patients and donors before HSCT. Two groups of seven patients each were selected, one in which individuals developed acute GVHD grades II-IV and one in which none showed any clinical signs of GVHD. Peripheral blood mononuclear cells (PBMCs) isolated from donors were incubated in mixed lymphocyte cultures (MLCs) with recipient PBMCs. The cells were characterized by flow cytometry before and after MLC.Results. Samples from donors in the GVHD group contained significantly lower frequencies of naïveγδT-cells and T-cells expressing NK-cell markers CD56 and CD94. Donor samples in this group also exhibited lower frequencies of naïve CD95+T-cells compared to controls. After MLC, there were dissimilarities in the CD4/CD8 T-cell ratio and frequency of CD69+T-cells between the two patient groups, with the non-GVHD group showing higher frequencies of CD8+and CD69+T-cells.Conclusion. We conclude that a thorough flow cytometric analysis of donor cells for phenotype and allogeneic reactivity may be of value when assessing pretransplant risk for severe acute GVHD.
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Sweden.
authors.forename: Darius
authors.identifier: 0000-0003-4855-2827
authors.initials: D
authors.lastname: Sairafi
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Sweden; Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Arwen
authors.identifier: 0000-0002-0251-5628
authors.initials: A
authors.lastname: Stikvoort
authors.affiliation: Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Gertow
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Sweden; Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Mattsson
authors.affiliation: Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Huddinge, Sweden.
authors.forename: Michael
authors.identifier: 0000-0002-2177-6727
authors.initials: M
authors.lastname: Uhlin
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016516:CD4-CD8 Ratio; D019002:CD56 Antigen / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000276:immunology; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D019002:CD56 Antigen; C497869:KLRD1 protein, human; C522918:NCAM1 protein, human; D051920:NK Cell Lectin-Like Receptor Subfamily D