Pediatric IBD patients show medication and disease activity dependent changes in NK cell and CD4 memory T cell populations.

Objectives: CD4+ memory T cells facilitate long-termed adaptive immune responses while NK cells are predominately rapid effector cells with significant functions for both intestinal homeostasis and inflammation. We wanted to study both populations in health and pediatric inflammatory bowel disease (IBD) and correlate them with disease activity and medication. Methods: We performed flow cytometric analyses of peripheral blood CD4 + CD45RO+ memory T cells and CD3-CD16 + CD56+ NK cells in 30 patients with IBD and 31 age-matched controls and correlated percentages of subsets with disease activity (PUCAI/PCDAI) and medication. Results: We found a significant reduction of peripheral NK cells in overall IBD patients with both clinical remission and disease activity, which was even more pronounced in patients treated with azathioprine. Otherwise, circulating CD4+ memory T cell populations were significantly enhanced in active IBD compared to controls. Enhancement of memory T cells was particularly found in new onset disease and correlated with disease activity scores. Discussion: Our single center cohort confirms previous results showing enhanced memory T cell populations in pediatric IBD patients, which correlate with disease activity scores. CD4+ memory T cells are a relevant pathogenic leukocyte population for disease development and perpetuation in IBD. In addition, we found a decrease of NK cells in IBD patients, which was pronounced by use of azathioprine. Surveillance of both cellular populations could possibly serve as biomarker for therapy control in pediatric IBD.

Atypical familial diabetes associated with a novel NEUROD1 nonsense variant.

OBJECTIVES: We aimed to identify the origin of atypical diabetes in a family with four generations of diabetes from South Asia. The family members showed different clinical phenotypes. Members of generation one to three were presumed to have type 2 diabetes and generation four to have type 1 diabetes. CASE PRESENTATION: We performed a genetic analysis of the family using targeted high throughput sequencing. CONCLUSIONS: We identified a novel nonsense variant in the neurogenic differentiation 1 (NEUROD1) gene, co-segregating with diabetes. The variant was located in the DNA-binding domain, altering a protein residue that was very well conserved among different species.