Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an anti-inflammatory molecule that negatively regulates the non-canonical nuclear factor-κB pathway. Although TRAF3 haploinsufficiency (TRAF3 HI) can influence innate and adaptive immune cells, its effect on inflammatory bowel disease (IBD) development remains unclear. Here, we report the first case of severe early-onset IBD with a novel TRAF3 variant leading to HI, successfully treated with ustekinumab. A 6-year-old girl with a recurrent parotitis, otitis media, tonsilitis, and atopic dermatitis developed IBD involving the stomach, small intestine, and colon. At diagnosis, the immunoglobulin (Ig)G and IgA levels were relatively high, and lymphocyte subsets showed increased counts of plasmablasts, class-switch recombination B cells, and circulating T-follicular helper cells. Treatment with azathioprine and infliximab failed to maintain remission marked by several relapses accompanied by erythema nodosum and arthritis; however, ustekinumab, an anti-interleukin (IL)-12/23p40 antibody, led to long-term clinical remission, normalizing the Ig level and reducing abnormal lymphocyte counts. Whole-exome sequencing revealed a novel heterozygous mutation in TRAF3 [p.(Pro487Leufs*8)], resulting in TRAF3 under-expression. Our case may highlight the contribution of TRAF3 HI to the development of IBD and provide insights into IBD pathophysiology, suggesting the involvement of the IL-12/23-T-follicular helper cell pathway affected by genetic mutations.

BACKGROUND: Meals are provided at nursery schools for Japanese preschool children, and this may result in different energy and nutrient intakes on weekdays and weekends. The purpose of this study was to obtain basic information for public nutrition policies in early childhood by examining differences in energy and nutrient intakes of preschool children between weekdays and weekends using meal categories such as breakfast, lunch, dinner, and snacks. METHODS: Energy and nutrient intakes were examined in 761 Japanese preschool children (423 boys, 338 girls) aged 3-6 years attending childcare facilities in seven regions in Japan. Data collection was based on non-consecutive four-day dietary records (two weekdays, two weekend days) in 2019 or 2020. Energy and nutrient intake by meal category were compared using a generalized linear mixed model adjusted for demographic factors. RESULTS: Total energy intake was significantly higher on weekdays for boys (1,478 vs. 1,415 kcal) and girls (1,349 vs. 1,296 kcal) (both P < 0.001). Weekday lunches had higher protein content and essential micronutrients such as potassium, iron, vitamins, and lower fat, saturated fatty acids, and salt, compared to weekend lunches. Similarly, weekday snacks also had significantly higher nutritional consumption for most nutrients compared to weekend equivalents. CONCLUSION These findings suggest that meals at nursery schools, particularly lunch and snacks, result in more desirable nutrient intake in preschool children. On weekdays, children consume meals with higher nutrient density, possibly due to the role of dietitians in menu planning. However, some children still fail to meet the Dietary Reference Intakes for Japanese, indicating a need for improvements in nursery school and home meals. More communication is needed between nursery schools and families, including sharing menus and recipes is essential. The results of this study are of value for development of public health nutrition strategies targeting early childhood.
Humans ; Child, Preschool ; Male ; Japan ; Female ; Energy Intake ; Meals ; Child ; Nutrients/analysis* ; Diet/statistics & numerical data* ; East Asian People