title: Prognostic value of apoptotic cells and infiltrating neutrophils in graft-versus-host disease of the gastrointestinal tract in humans: TNF and Fas expression.
abstract: The gastrointestinal (GI) tract is a major target in graft-versus-host disease (GvHD). In rodents both tumor necrosis factor (TNF) and Fas-dependent apoptosis have 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 pathologic analysis in 95 patients who underwent gastroduodenal biopsy. 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 for acute GvHD. In multivariate analysis, including pathologic 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 pathologic 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 II or higher acute liver GvHD. One-year TRM associated with the same 2 factors and with chronic GvHD.
authors.affiliation: Service d'Hématologie/Greffe de Moelle, INSERM ERM-0220, Université Paris VII and Hôpital Saint Louis, Paris, France. gsocie@chu-stlouis.fr
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Mary
authors.forename: Marc
authors.initials: M
authors.lastname: Lemann
authors.forename: Marjan
authors.initials: M
authors.lastname: Daneshpouy
authors.forename: Philippe
authors.initials: P
authors.lastname: Guardiola
authors.forename: Véronique
authors.initials: V
authors.lastname: Meignin
authors.forename: Lionel
authors.initials: L
authors.lastname: Ades
authors.forename: Hélène
authors.initials: H
authors.lastname: Esperou
authors.forename: Patricia
authors.initials: P
authors.lastname: Ribaud
authors.forename: Agnés
authors.initials: A
authors.lastname: Devergie
authors.forename: Eliane
authors.initials: E
authors.lastname: Gluckman
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Ameisen
authors.forename: Anne
authors.initials: A
authors.lastname: Janin
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D017209:Apoptosis; D002648:Child; D002675:Child, Preschool; D004064:Digestive System / Q000276:immunology / Q000473:pathology*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor