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.

Introduction: This study analyzed the reproducibility of residency training evaluation forms revised in FY 2020 using EPOC2.　Methods: Reproducibility was assessed by calculating the concordance rate and intraclass correlation coefficient (ICC) between evaluations from two clinical educators during the same clinical department rotation. Additionally, Bland-Altman plots were created to visualize the data.　Results: Out of 13,184 residents at facilities using EPOC2, approximately 3,800 who were evaluated more than twice by clinical educators during the same training period were analyzed. The average concordance rates for items A, B, and C were 68.6%, 43.8%, and 57.6%, respectively, indicating variability in evaluations among clinical educators. ICC values were also low.　Discussion: Our findings suggest that the reproducibility of evaluations was low and discrepancies among clinical educators’ assessments were evident. To improve reproducibility, we recommend increasing the number of evaluations by different clinical educators and strengthening clinical educator workshops.