Interleukin-7-dependent nonclassical monocytes and CD40 expression are affected in children with type 1 diabetes.

The important role of IL-7 in the generation of self-reactive T-cells in autoimmune diseases is well established. Recent studies on autoimmunity-associated genetic polymorphisms indicated that differential IL-7 receptor (IL-7R) expression of monocytes may play a role in the underlying pathogenesis. The relevance of IL-7-mediated monocyte functions in type 1 diabetes remains elusive. In the present study, we characterized monocyte phenotype and IL-7-mediated effects in children with type 1 diabetes and healthy controls with multicolor flow cytometry and t-distributed Stochastic Neighbor-Embedded (t-SNE)-analyses. IL-7R expression of monocytes rapidly increased in vitro and was boosted through LPS. In the presence of IL-7, we detected lower monocyte IL-7R expression in type 1 diabetes patients as compared to healthy controls. This difference was most evident for the subset of nonclassical monocytes, which increased after IL-7 stimulation. t-SNE analyses revealed IL-7-dependent differences in monocyte subset distribution and expression of activation and maturation markers (i.e., HLA-DR, CD80, CD86, CD40). Notably, monocyte CD40 expression increased considerably by IL-7 and CD40/IL-7R co-expression differed between patients and controls. This study shows the unique effects of IL-7 on monocyte phenotype and functions. Lower IL-7R expression on IL-7-induced CD40high monocytes and impaired IL-7 response characterize monocytes from patients with type 1 diabetes.

Remission of congenital hyperinsulinism following conservative treatment: an exploratory study in patients with KATP channel mutations.

BACKGROUND: During conservative treatment, congenital hyperinsulinism (CHI) can resolve spontaneously. This study describes the hormonal and metabolic profiles in three patients with ABCC8/KCNJ11 mutations in clinical remission. METHODS: An age-adapted fasting and oral glucose tolerance test (OGTT) were performed. RESULTS: All patients (aged 6-9 years) tolerated age-adapted fasting durations (20, respectively 24 h), without reaching glucose concentrations ≤2.5 mmol/L, nor developing hypoglycemia-related symptoms. Nevertheless, insulin concentrations from all patients exceeded the 90th reference percentile at the end of the fasting test (range: 4.2-15.8 mU/L). During the OGTT, one patient (patient 2; BMI: 23.4 kg/m2; age: 7 years) reached a glucose concentration of 11.4 mmol/L after 2 h (concomitant insulin concentration: 148.3 mU/L). CONCLUSIONS: The insulin concentration profiles in CHI patients in apparent clinical remission range from almost complete normalization to persistent, yet attenuated, hypersecretion. The hyperglycemia, detected during the OGTT, must be further monitored.