Post-transplant Inflammatory Bowel Disease Associated with Donor-Derived TIM-3 Deficiency.

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.

[Chronic inflammatory bowel disease in elderly people].

INTRODUCTION: Inflammatory bowel disease is mainly diagnosed in younger patients. However, the number of elderly patients (age > 60 years) affected by Crohn's disease or ulcerative colitis is increasing. In the elderly, symptoms often differ from the younger population. Older patients generally present a milder clinical course and are less often affected by extraintestinal disease activity. Treatment options are similar to the ones in younger patients. Due to the higher risk of drug interactions and side effects, comorbidities and comedication of the older patients play a pivotal role in the selection of the specific treatment agent. In therapy refractory disease, surgical treatment is also a valuable option for patients > 60 years. Furthermore, vaccination, prevention of infections and regular cancer screening is mandatory in this vulnerable population.