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Can NOD2/CARD15 mutations predict intestinal graft-versus-host disease and aid our understanding of Crohn's disease?

Nature Clinical Practice Gastroenterology & Hepatology volume 1, pages 62–63 (2004)Cite this article

Acute graft-versus-host disease (GvHD) remains the major cause of morbidity and mortality following allogeneic bone marrow transplantation and blood stem cell transplantation (SCT). Although donor T cells have been recognized as the central effector cells of GvHD, activation and induction of this disease almost exclusively depends on activation of host antigen-presenting cells (APCs).1 Activation of APCs occurs in response to various danger signals. In the setting of SCT, conditioning mediated cytokine release and the presence of viruses and bacterial toxins are the most important danger signals.

The intestinal mucosa has been one focus of GvHD pathophysiology. Initially this was attributed to the presence of crossreacting antigens on intestinal bacteria and the gut epithelial tissue, or endotoxin-mediated release of cytokines, such as tumor necrosis factor α (TNF-α) in GvHD-related pathology.2 Since a reduced incidence of complications in patients treated in a protected environment was demonstrated, GNOTOBIOSIS has become an important preventive strategy in allogeneic SCT. The real impact of gnotobiosis on clinical GvHD has never been proven in larger studies and is still a matter of debate. New experimental data, however, strongly support a central role of the gastrointestinal tract in GvHD because knockout animals that are deficient for adhesion molecules relevant for the homing of T cells in Peyer's patches do not develop GvHD at all.3

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Authors and Affiliations

  1. Professor of Gastroenterology and Head of the Gastroenterological Unit Department of Internal Medicine I, University of Regensburg, Germany

    Gerhard Rogler

  2. Professor of Hematology and Head of the Bone Marrow Transplantation Unit, at the Department of Internal Medicine I, University of Regensburg, Germany

    Ernst Holler

Authors
  1. Gerhard Rogler
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  2. Ernst Holler
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Corresponding author

Correspondence to Gerhard Rogler.

Glossary

GNOTOBIOSIS

Strategy of modulating patients' flora by complete or selective decontamination and a protective environment

PROFESSIONAL APCs

Antigen-presenting dendritic cells or macrophages

CHRONIFICATION

Pathophysiological process of developing chronic (mucosal) T-cell driven inflammation after acute (macrophage) driven inflammation

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Rogler, G., Holler, E. Can NOD2/CARD15 mutations predict intestinal graft-versus-host disease and aid our understanding of Crohn's disease?. Nat Rev Gastroenterol Hepatol 1, 62–63 (2004). https://doi.org/10.1038/ncpgasthep0042

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