Citrobacter rodentium is a gastrointestinal infection that requires early IL-22 from group 3 innate lymphoid cells (ILC3) for resistance. The role of vitamin D in the clearance of C. rodentium infection was tested in vitamin D sufficient (D+) and vitamin D deficient (D-) wildtype (WT) and Cyp27B1 (Cyp) KO mice (unable to produce the high affinity vitamin D ligand 1,25(OH)2D, 1,25D). Feeding Cyp KO mice D- diets reduced vitamin D levels and prevented synthesis of 1,25D. D- (WT and Cyp KO) mice had fewer ILC3 cells and less IL-22 than D+ mice. D- Cyp KO mice developed a severe infection that resulted in the lethality of the mice by d14 post-infection. T and B cell deficient D- Rag KO mice also developed a severe and lethal infection with C. rodentium compared to D+ Rag KO mice. D- WT mice survived the infection but took significantly longer to clear the C. rodentium infection than D+ WT or D+ Cyp KO mice. Treating infected D- Cyp KO mice with IL-22 protected the mice from lethality. Treating the D- WT mice with 1,25D reconstituted the ILC3 cells in the colon and protected the mice from C. rodentium. IL-22 treatment of D- WT mice eliminated the need for vitamin D to clear the C. rodentium infection. Vitamin D is required for early IL-22 production from ILC3 cells and protection from enteric infection with C. rodentium.

Primary hepatic lymphoma (PHL) is an extremely rare manifestation of extranodal non-Hodgkin's lymphoma (0.016% of all cases). Presented are CT, MRI, ultrasound, and (18)F fluoro-2-deoxy-D-glucose (FDG) PET/CT images, which characterized PHL and demonstrated hepatic vein thrombus that extended into the inferior vena cava--a feature not previously described. Recognition of this imaging pattern may help in the differential diagnosis of future such cases. FDG PET/CT was critical in confirming the diagnosis, staging, and demonstrating response to treatment.

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The Hospital for Sick Children, 5 Montreal Children. RATIONALE: Birch allergy affects up to a third of Canadians (Lok et al J Asthma 2017). Cross reaction between birch pollen and certain tree nut allergens mainly hazelnut may contribute to false positive skin tests as well as pollen-food syndrome and mislabeling patients as having a lifethreatening allergy to hazelnut. We aimed to determine the usefulness of double-blind, placebo-controlled food challenge (DBPCFC) in the diagnosis of primary hazelnut allergy (HA) in our oral immunotherapy study cohort. METHODS: We conducted DBPCFC in 9 children (median age 15, and IQR 9-17) with previous history of an IgE-mediated reaction to hazelnut with positive skin test and/or specific IgE (sIgE) as well as 22 children (median age 12, IQR 10-14) with peanut allergy (PA) referred by allergists as controls because cross-reaction with common allergens like birch pollen in PA is less likely. Four HA children and 11 PA children were male. Additional patient demographics, skin prick test, sIgE, and adverse events were also documented. Fisher's exact test was used for analysis of binary variables. RESULTS: Six out of 9 HA patients tolerated DBPCFC while no PA patient did (P<0.001). Adverse reactions were mild in the hazelnut challenge with no use of epinephrine. In contrast, anaphylactic adverse reactions (> _ 2 organ systems involved) occurred to 21 PA patients with epinephrine use in 16 out of 22 patients (P<0.05). CONCLUSIONS: DBPCFC is required for the diagnosis of HA and hazelnuts are less likely to cause severe allergic reactions compared to peanuts. Tree nut allergy needs to be investigated individually.

RATIONALE: The Runx1 transcription factor decreases GATA3 and IL-4 expression and Th2 skewing and promotes Th1/Th17/Tregulatory (Treg) cell development and function. We hypothesized that patients with germline RUNX1 deficiency would be predisposed to allergic and/or autoimmune disease. METHODS: Thirty-one patients (17 female; median age 42 years, range 2-74) with confirmed RUNX1 mutations were evaluated. Peripheral blood was obtained to evaluate hematologic variables, total and allergen specific IgE, and lymphocyte immune phenotypes. RESULTS: 29/31 patients had a positive allergic history; 21 had allergic rhinitis, 16 allergic conjunctivitis, and 20 mild-moderate eczema controlled with topical glucocorticoids and emollients. Seven patients had doctordiagnosed asthma with 1 patient receiving mepolizumab for eosinophilic asthma. Four reported oral allergy syndrome. Two patients had IgEmediated food allergy to flounder and egg, respectively, and two had biopsy-proven eosinophilic esophagitis. Five patients reported autoimmune disorders including mixed connective tissue disease, Hashimoto's thyroiditis, Sjogren's syndrome, alopecia universalis and systemic Juvenile idiopathic arthritis. Median total IgE and eosinophil counts were within the normal range (73.35 IU/mL; range 16 -635 IU/mL and 215/mcL; range 0-1000/mcL, respectively). Median CD4 and CD8 T cells counts were within the normal range, although patients exhibited an increased frequency of memory CD4+ T cells, decreased CD4:CD8 ratios, and decreased Tregs in peripheral blood when compared to healthy controls. CONCLUSIONS: Patients with germline RUNX1 deficiency exhibit an increased prevalence of atopic and autoimmune disorders, demonstrating an important role for Runx1 in tolerance development in humans.