Samuel H. Masur

Inflammatory CD4(+) T cell responses to self or commensal bacteria underlie the pathogenesis of autoimmunity and inflammatory bowel disease (IBD), respectively. Although selection of self-specific T cells in the thymus limits responses to mammalian tissue antigens, the mechanisms that control selection of commensal bacteria-specific T cells remain poorly understood. Here, we demonstrate that group 3 innate lymphoid cell (ILC3)-intrinsic expression of major histocompatibility complex class II (MHCII) is regulated similarly to thymic epithelial cells and that MHCII(+) ILC3s directly induce cell death of activated commensal bacteria-specific T cells. Further, MHCII on colonic ILC3s was reduced in pediatric IBD patients. Collectively, these results define a selection pathway for commensal bacteria-specific CD4(+) T cells in the intestine and suggest that this process is dysregulated in human IBD.

OBJECTIVES: Infliximab (IFX) is commonly used to treat children with inflammatory bowel disease (IBD). We previously reported that patients with extensive disease started on IFX at a dose of 10 mg/kg had greater treatment durability at year one. The aim of this follow-up study is to assess the long-term safety and durability of this dosing strategy in pediatric IBD. METHODS: We performed a retrospective single-center study of pediatric IBD patients started on IFX over a 10-year period. RESULTS: Two hundred ninety-one patients were included (mean age = 12.61, 38% female) with a follow-up range of 0.1-9.7 years from IFX induction. One hundred fifty-five (53%) were started at a dose of 10 mg/kg. Only 35 patients (12%) discontinued IFX. The median duration of treatment was 2.9 years. Patients with ulcerative colitis ( P ≤ 0.01) and patients with extensive disease ( P = 0.01) had lower durability, despite a higher starting dose of IFX ( P = 0.03). Adverse events (AEs) were observed to occur at a rate of 234 per 1000 patient-years. Patients with a higher serum IFX trough level (≥20 µg/mL) had a higher rate of AEs ( P = 0.01). Use of combination therapy had no impact on risk of AEs ( P = 0.78). CONCLUSIONS: We observed an excellent IFX treatment durability, with only 12% of patients discontinuing therapy over the observed timeframe. The overall rate of AEs was low, the majority being infusion reactions and dermatologic conditions. Higher IFX dose and serum trough level> 20 µg/mL were associated with higher risk of AEs, the majority being mild and not resulting in cessation of therapy.

Sweet's syndrome (acute febrile neutrophilic dermatosis) is a rare disorder of unclear aetiology characterised by painful cutaneous lesions, sometimes accompanied by systemic symptoms. It has been associated with several autoimmune conditions, drugs, malignancies and infections, though many cases are idiopathic. We describe a case of Sweet's syndrome in a 49-year-old man with pre-existing psoriasis following recent initiation of risankizumab therapy. There are very few reported cases of Sweet's syndrome in association with psoriasis and no existing reports in association with an IL-23 inhibiting medication. Further investigation of the potentially overlapping immunologic pathways implicated in cutaneous reactions to biologic agents and autoimmune conditions such as psoriasis may yield insights into the pathogenesis of such conditions and guide advancements in the rapidly evolving field of targeted biologic therapies.

Case Summary: A 23-year-old female with common variable immunodeficiency (CVID), presented with intermittent epigastric pain, which would eventually spread to her entire abdomen. She had night sweats, chills, and regular stools. She had been evaluated twice over the last two months for posterior cervical lymphadenopathy and similar abdominal symptoms, which were attributed to a possible EBV infection. Her exam was notable for diffuse abdominal tenderness, worse in the epigastric region, without rebound or guarding. Additionally, she had a non-tender fixed lymph node in the right posterior cervical chain. Her medical …