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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., Introduction IKAROS, a transcription factor encoded by IKZF1, is expressed during hematopoiesis (1, 2). It has been involved in positive regulation of lymphocyte differentiation and negative regulation of cell proliferation [...]

Objective Examine the 24-hr Recall Interview (24R1) for assessing children's antiretroviral medication adherence. Methods Caregivers of 54 children with HIV (aged 2-12 years) completed a clinical adherence interview and the 24R1 by telephone. Children's viral load and 3-month pharmacy records were obtained. Results Thirty-seven percent of children missed ⩾1 dose of medicine over 3 days. In 22% of the samples, adherence varied across medications. The 24R1 adherence scores (Frequency, Interval, and Dietary Adherence) were moderately reliable across the three interviews. Pharmacy refill rates were significantly related to viral load, and 24R1 barriers were marginally significantly related to viral load. Conclusions The 24R1, with its systematic, cued recall, and decreased focus on adherence, may reduce socially desirable responding compared to other self-report methods, and reporting adherence barriers may indicate adherence difficulty. However, the validity of the 24R1 must be improved to make it a useful measure to include in an adherence assessment battery. [ABSTRACT FROM AUTHOR]