Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients.

Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who demonstrated variable clinical penetrance. Reduced transcriptional activity of pathogenic variants confirmed partial or complete PAX1 deficiency. Thymic aplasia and hypoplasia were associated with impaired T cell immunity. Corrective treatment was required in 4/6 patients. Hematopoietic stem cell transplantation resulted in poor immune reconstitution with absent naïve T cells, contrasting with the superior recovery of T cell immunity after thymus transplantation. Normal ex vivo differentiation of PAX1-deficient CD34+ cells into mature T cells demonstrated the absence of a hematopoietic cell-intrinsic defect. New overlapping features with DiGeorge syndrome included primary hypoparathyroidism (n = 5) and congenital heart defects (n = 2), in line with PAX1 expression during early embryogenesis. Our results highlight new features of PAX1 deficiency, which are relevant to improving early diagnosis and identifying patients requiring corrective treatment.

Cold-induced urticaria in children: A multicenter, retrospective cohort study.

Background: Studies of cold-induced urticaria (ColdU) in pediatric patients are limited and not well characterized. Objective: The objective of the study was to investigate the characteristics of ColdU in children. Methods: A multicenter, retrospective chart review was performed in children ages ≤18 years diagnosed with ColdU at 11 pediatric allergy and immunology centers in Turkey between September 1, 2010, and August 31, 2022. Results: A total of 83 children with ColdU were included, 54.2% were girls, and the mean age of symptom onset was 8.8 years. The median duration of ColdU at the time of diagnosis was significantly higher in the girls than in the boys (1.0 years [0.0-13.8 years] versus 0.3 years [0.0-15.0 years]; p = 0.007). All the patients underwent an ice cube test, and 71.1% were found positive (typical ColdU). The mean ± standard deviation age of onset was significantly higher in the patients with typical ColdU versus atypical patients (9.4 ± 4.5 years versus 7.3 ± 4.5 years; p = 0.041). Swimming alone and in combination with the wind were significantly the most reported triggers in patients with cold-induced anaphylaxis (ColdA) when compared with patients with ColdU and with nonanaphylactic symptoms (70.0% versus 28.9% [p = 0.022], and 50.0% versus 4.1% [p < 0.001], respectively). Only patients with other chronic urticaria were found to be associated with the development of typical ColdU (p = 0.036). The median total serum immunoglobulin E (IgE) was significantly higher in typical ColdU than in atypical patients (72.5 IU/mL [3.86 - 2500 IU/mL] versus 30.0 IU/mL [0.83 - 1215 IU/mL]; p = 0.007); however, total serum IgE differences were not found to affect ColdU resolution between the two groups (p = 0.204). The resolution was documented in 30.4%. Conclusion: Those who were boys and had a positive ice cube test result could have an association with earlier onset of ColdU. Those swimming alone on a windy day were at highest risk for ColdA. It is still unclear what characteristics are associated with the resolution of ColdU, and this warrants further investigation.