title: Identification and validation of biomarkers associated with acute and chronic graft versus host disease.
abstract: Graft versus host disease (GVHD) is a major complication of haematopoietic SCT (HSCT). A number of inflammatory cytokines/chemokines are implicated in GVHD and have been identified in numerous single centre studies as potential biomarkers for acute and/or chronic GVHD. In this study, we analysed candidate inflammatory biomarkers (B-cell activating factor (BAFF), interleukin 33 (IL-33), CXCL10 and CXCL11) in a two-centre study. Biomarkers were evaluated pre-transplant and at serial time points post transplant in acute and chronic GVHD patient sera with time-matched control samples from patients without GVHD. Further validation was performed using the human skin explant assay, clinical GVHD biopsies and mRNA expression analysis. BAFF was significantly increased pre-transplant. BAFF, IL-33, CXCL10 and CXCL11 showed increased levels in acute GVHD patient sera and high protein expression in grades II-III of the in vitro skin explant graft versus host reaction (GVHR) group. BAFF, CXCL10 and CXCL11 also showed increased mRNA expression levels in clinical biopsies compared with the no/low-grade GVHD group. BAFF, CXCL10 and CXCL11 levels were increased in chronic GVHD patient sera. The results identify BAFF and CXCL10 as predictive biomarkers for acute GVHD and BAFF, CXCL10 and CXCL11 as useful diagnostic biomarkers for acute GVHD and chronic GVHD.
authors.affiliation: Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.|Alcyomics Ltd, Newcastle-upon-Tyne, UK.
authors.forename: S S
authors.initials: SS
authors.lastname: Ahmed
authors.affiliation: Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.|Alcyomics Ltd, Newcastle-upon-Tyne, UK.
authors.forename: X N
authors.initials: XN
authors.lastname: Wang
authors.affiliation: Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: J
authors.initials: J
authors.lastname: Norden
authors.affiliation: Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: K
authors.initials: K
authors.lastname: Pearce
authors.affiliation: Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: E
authors.initials: E
authors.lastname: El-Gezawy
authors.affiliation: Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: S
authors.initials: S
authors.lastname: Atarod
authors.affiliation: Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: I
authors.initials: I
authors.lastname: Hromadnikova
authors.affiliation: Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: M
authors.initials: M
authors.lastname: Collin
authors.affiliation: Regensburg University Hospital, Department of Hematology and Oncology, Regensburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Holler
authors.affiliation: Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.|Alcyomics Ltd, Newcastle-upon-Tyne, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Dickinson
mesh_terms: D000208:Acute Disease; D064591:Allografts; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D016207:Cytokines; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000175:diagnosis* / Q000209:etiology; D019337:Hematologic Neoplasms / Q000097:blood / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male
chemical_list: D015415:Biomarkers; D016207:Cytokines