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J Clin Immunol ; 44(3): 63, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38363399

ABSTRACT

Inflammatory bowel disease (IBD) occurring following allogeneic stem cell transplantation (aSCT) is a very rare condition. The underlying pathogenesis needs to be better defined. There is currently no systematic effort to exclude loss- or gain-of-function mutations in immune-related genes in stem cell donors. This is despite the fact that more than 100 inborn errors of immunity may cause or contribute to IBD. We have molecularly characterized a patient who developed fulminant inflammatory bowel disease following aSCT with stable 100% donor-derived hematopoiesis. A pathogenic c.A291G; p.I97M HAVCR2 mutation encoding the immune checkpoint protein TIM-3 was identified in the patient's blood-derived DNA, while being absent in DNA derived from the skin. TIM-3 expression was much decreased in the patient's serum, and in vitro-activated patient-derived T cells expressed reduced TIM-3 levels. In contrast, T cell-intrinsic CD25 expression and production of inflammatory cytokines were preserved. TIM-3 expression was barely detectable in the immune cells of the patient's intestinal mucosa, while being detected unambiguously in the inflamed and non-inflamed colon from unrelated individuals. In conclusion, we report the first case of acquired, "transplanted" insufficiency of the regulatory TIM-3 checkpoint linked to post-aSCT IBD.


Subject(s)
Hepatitis A Virus Cellular Receptor 2 , Inflammatory Bowel Diseases , Stem Cell Transplantation , Humans , Cytokines/metabolism , Hepatitis A Virus Cellular Receptor 2/genetics , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/etiology , Intestinal Mucosa , Stem Cell Transplantation/adverse effects
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