Advances in understanding the pathogenesis of graft-versus-host disease

Br J Haematol. 2016 Apr;173(2):190-205. doi: 10.1111/bjh.13959. Epub 2016 Mar 27.

Abstract

Allogeneic haematopoietic stem cell transplantation (HCT) is a potent immunotherapy with curative potential for several haematological disorders. Overcoming the immunological barrier of acute graft-versus-host disease (GVHD) remains a fundamental impediment to expanding the efficacy of HCT. GVHD reflects a complex pathological interaction between the innate and adaptive immune systems of the host and donor. Over the past decade there has been a tremendous advancement in our understanding of the cellular and molecular underpinnings of this devastating disease. In this review, we cover several recently appreciated facets of GVHD pathogenesis including novel extracellular mediators of inflammation, immune subsets, intracellular signal transduction, post-translation modifications and epigenetic regulation. We begin to develop general themes regarding the immunological pathways in GVHD pathogenesis, discuss critical outstanding questions, and explore new avenues for GVHD treatment and prevention.

Keywords: GVHD; allogeneic; transplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • B-Lymphocytes / immunology
  • Biomarkers / metabolism
  • Cell Communication / immunology
  • Chemokines / immunology
  • Cytokines / immunology
  • Graft vs Host Disease / etiology*
  • Graft vs Host Disease / immunology
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Immunity, Innate / immunology
  • Microbiota / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Transplantation Immunology / immunology
  • Transplantation, Homologous / adverse effects

Substances

  • Biomarkers
  • Chemokines
  • Cytokines