Ikaros/IKZF1 is an essential transcription factor expressed throughout hematopoiesis. IKZF1 is implicated in lymphocyte and myeloid differentiation and negative regulation of cell proliferation. In humans, somatic mutations in IKZF1 have been linked to the development of B cell acute lymphoblastic leukemia (ALL) in children and adults. Recently, heterozygous germline IKZF1 mutations have been identified in patients with a B cell immune deficiency mimicking common variable immunodeficiency. These mutations demonstrated incomplete penetrance and led to haploinsufficiency. Herein, we report 7 unrelated patients with a novel early-onset combined immunodeficiency associated with de novo germline IKZF1 heterozygous mutations affecting amino acid N159 located in the DNA-binding domain of IKZF1. Different bacterial and viral infections were diagnosed, but Pneumocystis jirovecii pneumonia was reported in all patients. One patient developed a T cell ALL. This immunodeficiency was characterized by innate and adaptive immune defects, including low numbers of B cells, neutrophils, eosinophils, and myeloid dendritic cells, as well as T cell and monocyte dysfunctions. Notably, most T cells exhibited a naive phenotype and were unable to evolve into effector memory cells. Functional studies indicated these mutations act as dominant negative. This defect expands the clinical spectrum of human IKZF1-associated diseases from somatic to germline, from haploinsufficient to dominant negative.

High levels of total n-6 polyunsaturated fatty acids (PUFAs) in breast milk are associated with an increased risk for AS, whereas high levels of total n-3 PUFAs decreased the risk of atopy. These data suggest that the effects of n-3 and n-6 PUFAs on allergic disorders should be further explored.

The findings from this large, international patient registry documented widespread implementation of pnfC1-INH self-administration outside of a health care setting consistent with current HAE guidelines. These real-world data revealed pnfC1-INH usage for a variety of reasons in patients with HAE and showed a high level of safety regardless of administration setting or reason for use.

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BackgroundTo assess the relationship between any systemic antibiotic prescription within the first year of life and the presence of an ICD-9-CM diagnosis code for food allergy (FA).MethodsThis was a matched case–control study conducted using South Carolina Medicaid administrative data. FA cases born between 2007 and 2009 were matched to controls without FA on birth month/year, sex, race/ethnicity. Conditional logistic regression was used to model the adjusted odds ratio (aOR) of FA diagnosis. All models were adjusted for presence of asthma, wheeze, or atopic dermatitis.ResultsA total of 1504 cases and 5995 controls were identified. Receipt of an antibiotic prescription within the initial 12 months of life was associated with FA diagnosis in unadjusted and adjusted models (aOR 1.21; 95 % CI 1.06–1.39). Compared to children with no antibiotic prescriptions, a linear increase in the aOR was seen with increasing antibiotic prescriptions. Children receiving five or more (aOR 1.64; 95 % CI 1.31–2.05) antibiotic prescriptions were significantly associated with FA diagnosis. The strongest association was noted among recipients of cephalosporin and sulfonamide antibiotics in both unadjusted and adjusted models.ConclusionsReceipt of antibiotic prescription in the first year of life is associated with FA diagnosis code in young children after controlling for common covariates. Multiple antibiotic prescriptions are more strongly associated with increases in the odds of FA diagnosis.