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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.

Background: The management of hereditary angioedema has rapidly changed over the past decade. With these changes there has been increased recognition of the unique challenges of diagnosing and managing hereditary angioedema in pediatric populations. The objective of this review was to identify and compare recently published consensus guidelines for the management of hereditary angioedema types 1 and 2 to identify areas of agreement and conflict. Methods: A MEDLINE database search was performed to identify guidelines that offered guidance on diagnosing or managing hereditary angioedema in pediatric populations. A limitation was placed on guidelines published in the past 5 years to reflect the most recent literature. Results: Six clinical practice guidelines were included in the analysis. Early detection of disease status, coordination with specialists, and empowering patients with self-administered medications are emphasized, with use of plasma derived C1 esterase inhibitor as first line therapy for aborting attacks. The guidelines are shifting away from attenuated androgens and tranexamic acid for long-term prophylaxis toward medications such as subcutaneous C1 esterase inhibitor, lanadelumab, and berotralstat. Conclusion: Although some differences exist based on geographic region and health system where an included guideline was published, they have very minimal differences on close review.