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Graft-Versus-Host Disease

Identification and validation of biomarkers associated with acute and chronic graft versus host disease

Bone Marrow Transplantation volume 50, pages 1563–1571 (2015)Cite this article

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A Corrigendum to this article was published on 01 June 2016

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.

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Acknowledgements

We thank Elizabeth Douglas, Cindy Carr for technical support, Shelagh Lowerson for providing Clinical Data from Euro Bank and help with ROC analysis and Shazmeen Surtee for helping as part of her undergraduate project. This study was funded by FP6 EC Stemdiagnostics (Contract No. 037703), FP7 Marie Curie Initial Training Network Celleurope (Contract No. 315963), Leukemia and Lymphoma Research and Tyneside Leukaemia Research Association.

Author contributions

SSA, XNW, JN and EE-G performed experiments. SSA, KP and SA carried out the statistical analysis. SSA and AMD wrote the paper. EH, MC and IH contributed to collaborating on the research and contributed patient samples and clinical data. AMD and EH designed the research.

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Authors and Affiliations

  1. Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK

    S S Ahmed, X N Wang, J Norden, K Pearce, E El-Gezawy, S Atarod, M Collin & A M Dickinson

  2. Alcyomics Ltd, Newcastle-upon-Tyne, UK

    S S Ahmed, X N Wang & A M Dickinson

  3. Third Faculty of Medicine, Charles University, Prague, Czech Republic

    I Hromadnikova

  4. Department of Hematology and Oncology, Regensburg University Hospital, Regensburg,, Germany

    E Holler

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  1. S S Ahmed
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Correspondence to A M Dickinson.

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Ahmed, S., Wang, X., Norden, J. et al. Identification and validation of biomarkers associated with acute and chronic graft versus host disease. Bone Marrow Transplant 50, 1563–1571 (2015). https://doi.org/10.1038/bmt.2015.191

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