Summary:
Intestinal immunopathology was studied after allogeneic stem cell transplantation (SCT) in a common clinical setup in 20 children with malignant (n=17) or nonmalignant diseases (n=3) receiving grafts from siblings (7) and unrelated donors (13). In all, 19 had total body irradiation. Duodenal biopsies at 6 and 12 weeks post transplant were evaluated by histology, immunohistochemistry, and ISEL for the detection of T-lymphocytes, inflammatory cytokines, proliferation, and apoptosis. The controls were 12 healthy children and three patients with proven intestinal graft-versus-host disease. An increased rate of apoptosis and proliferation with upregulated expression of HLA-DR antigen was detected up to 3 months post transplant in the SCT patients, even in those with a histologically normal small intestine. A low level of IFNγ and TNFα was observed in the lamina propria. The initial low density of γδ-positive T cells had recovered to normal by the time of the second endoscopy at 12 weeks post transplant. We conclude that inflammatory activity and T cell infiltration detected by immunohistochemistry may not belong to the ‘normal’ recovery of the small intestine after SCT. Increased cell turnover in the intestinal crypts continues until 3 months after SCT, suggesting either an unexpectedly long-lasting effect of transplant-related toxicity or, preferably, an ongoing subclinical alloreactive process, also present in the patients without intestinal symptoms.
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Acknowledgements
The skillful technical assistance of Ms Sirkku Kristiansen is acknowledged. This study was financially supported by the Nona and Kullervo Väre Foundation (MT), the Finnish Cancer Foundation (MT), the Foundation of the Friends of the University Children's Hospitals in Finland (MW-O), and the Finnish Medical Association (MW-O), and Research Funding of the Helsinki University Hospitals (USP, MT), which is gratefully acknowledged.
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Taskinen, M., Westerholm-Ormio, M., Karikoski, R. et al. Increased cell turnover, but no signs of increased T-cell infiltration or inflammatory cytokines in the duodenum of pediatric patients after allogeneic stem cell transplantation. Bone Marrow Transplant 34, 221–228 (2004). https://doi.org/10.1038/sj.bmt.1704559
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DOI: https://doi.org/10.1038/sj.bmt.1704559