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Prepublished online as a Blood First Edition Paper on July 24, 2003; DOI 10.1182/blood-2003-03-0909.
Submitted March 25, 2003
Accepted July 8, 2003
Graft-versus-host disease of the gastro-intestinal tract in humans: TNF and Fas expression; prognostic value of apoptotic cells and infiltrating neutrophils
Gerard Socie*, Jean-Yves Mary, Marc Lemann, Marjan Daneshpouy, Philippe Guardiola, Veronique Meignin, Lionel Ades, Helene Esperou, Patricia Ribaud, Agnes Devergie, Eliane Gluckman, Jean-Claude Ameisen, and Anne Janin
Department of Hematology-Transplantation, Hospital St Louis, Paris, France; INSERM-ERM-0220, Paris, France
INSERM-ERM-0321, Paris, France
Department of Gastroenterology, Hospital St Louis, Paris, France
Department of Pathology, Hospital St Louis, Paris, France
INSERM-EMI 9922, Paris, France
* Corresponding author; email: gsocie{at}chu-stlouis.fr.
The gastro-intestinal (GI) tract is a major target in graft-versus-host disease (GvHD). In rodents both TNF and Fas-dependent apoptosis has been shown to play a major role in GvHD lesions, but data in humans on TNF- and Fas- in situ expression are scarce. More recently, the role of non-T cells as GvHD effectors has also been suggested in experimental models. Here we report a detailed quantitative pathological analysis in 95 patients who had gastro-duodenal biopsies. This analysis included characterization and quantification of the cellular infiltrate, TNF, TNF-receptors and Fas in situ expression analyses, and quantification of apoptotic cell numbers. TNF was expressed in all biopsies and it was highly specific of acute GvHD. In multivariate analysis, including pathological factors only, increased early transplant-related mortality (TRM) was associated with the presence of more than 20 neutrophils per field. Factors affecting early and late TRM were then assessed by multivariate analyses including both pathological and clinical factors. Increased day 90 TRM was associated with the presence of more than 5 apoptotic bodies per field within the cellular infiltrate, and with stage 2 or more acute liver GvHD. One year TRM associated with the same two factors and with chronic GvHD.
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