A Novel Homozygous Germline Mutation in Transferrin Receptor 1 (TfR1) Leads to Combined Immunodeficiency and Provides New Insights into Iron-Immunity Axis.

A homozygous missense mutation in the transferrin receptor 1 (TfR1), also known as CD71, leads to a rare inborn error of immunity (IEI) characterized by the impaired lymphocyte activation and proliferation due to defective iron uptake of cells. However, only one causative mutation (c.58T > C, p.Y20H) in the TFRC gene coding for TfR1 has been reported so far. We herein identified a new disease-causing homozygous germline mutation in the TFRC gene (c.64C > T, p.R22W) (referred to as TfR1R22W from now on) in a Turkish patient with combined immunodeficiency (CID). TfR1R22W results in impaired TfR1 internalization similar to previously defined TfR1Y20H mutation. We found that TfR1R22W is associated with severely restricted B and T lymphocyte clonal diversity and impaired T cell activation and cytokine production as well as defective mitochondrial oxidative phosphorylation in helper T cells. In addition, circulating NK, Treg, and MAIT cell populations were significantly decreased in the patient. Using whole transcriptome analysis, we found dysregulated immune homeostasis and novel biological processes associated with TfR1R22W. We also identified a considerable expansion of circulating low-density neutrophils (LDNs) in patient's PBMCs. Overall, TfR1R22W mutation expands the current understanding of the IEI associated with TfR1 dysfunction and provides new insights underlying impaired immune function, lymphocyte diversity, and granulocyte homeostasis.

The Asthma Risk Is Increased in Children with Severe Allergic Rhinitis.

OBJECTIVE: The aim of the study was to evaluate the allergic rhinitis severity, to identify risk fac- tors associated with asthma, and to determine the frequency of comorbid conditions in allergic rhinitis patients with positive skin prick test. MATERIALS AND METHODS: Clinical characteristics of pediatric patients with allergic rhinitis were investigated. The frequency of comorbidities and risk factors for asthma development were investigated. RESULTS: A total of 120 patients with a mean age of 13.05 ± 3.20 years were included in the study. Dermatophagoides pteronyssinus was the most common source of allergic sensitization (n = 78, 61.0%), whereas mild-persistent disease was the most common type of allergic rhini- tis severity (n = 44, 36.6%). Sensitization to Dermatophagoides farinea, Dermatophagoides pteronyssinus, and Alternaria was more common in patients with a moderate-severe course of allergic rhinitis than in the mild group (P = .006, P = .008, and P = .005, respectively). The most frequent comorbidity in children with allergic rhinitis was allergic conjunctivitis (71.7%). The inci- dence of asthma in those with moderate-severe allergic rhinitis was found to be significantly higher compared to those with mild disease severity (P = .009). Also, the multivariate analysis disclosed moderate-severe allergic rhinitis severity and persistent allergic rhinitis symptoms (OR: 3.822; 95% CI: 1.587-9.200; P =0.003 and OR: 0.333; 95% CI: 0.150-0.737; P =.007, respec- tively) as risk factors for asthma development. CONCLUSION: Sensitization to Dermatophagoides farinea, Dermatophagoides pteronyssinus, and Alternaria was more frequent in patients with moderate-severe allergic rhinitis course. Also, having moderate-severe allergic rhinitis severity and persistent allergic rhinitis symptoms are associated with the development of asthma. Awareness of the risk factors could prevent the progression and complications of allergic rhinitis in children.

Evaluation of Noncystic Fibrosis Bronchiectasis Using Clinical and Radiological Scorings in Children.

OBJECTIVES: The aim of this study was to evaluate radiological, clinical, and demographic data of patients with noncystic fibrosis bronchiectasis and to compare high-resolution computed tomography (HRCT) scores based on the demographic and clinical characteristics. MATERIALS AND METHODS: A total of 34 patients (18 male, 16 female) were assessed in terms of age at symptom onset, age at diagnosis, annual attack frequency, cough severity score, physical examination findings, and pulmonary function test results. Modified Bhalla scoring system (B total) and anatomical prevalence degree score (D total) were used for HRCT examination. RESULTS: There was a strong negative correlation between forced expiratory volume at first second (FEV1) and bronchial dilatation degree (SBRDIL). There was a moderate negative correlation of FEV1, forced vital capacity (FVC), and maximum mid-expiratory flow rate (MEF; 25-75) with bronchiectasis degree (EXBRNC), bronchial wall thickness degree (SBWTHICK), and mucus accumulation in the major airways (PMPLA). The B total, D total, EXBRNC, and SBRDIL scores were significantly higher in patients with hemoptysis and sputum. In comparing B and D total scoring systems, B total provided better results in terms of rale, annual exacerbation frequency (AEF), cough severity score (CSS), and FEV1 values. CONCLUSION: As it is proved using HRCT, pulmonary function impairment, sputum production, hemoptysis, and increase in AEF strongly correlating with objective HRCT scoring can be accepted as markers for pathological changes due to bronchiectasis.

Normal sweat chloride test does not rule out cystic fibrosis.

Basaran AE, Karatas-Torun N, Maslak IC, Bingöl A, Alper ÖM. Normal sweat chloride test does not rule out cystic fibrosis. Turk J Pediatr 2017; 59: 68-70. A 5-month-old patient presented with complaints of fever and cough. He was hospitalized with the diagnosis of bronchopneumonia and pseudo-Bartter's syndrome. Patient was further investigated for diagnosis of cystic fibrosis. The chloride (Cl) level in sweat was determined within the normal range (25.1 mmol/L, 20.3 mmol/L). CFTR (Cystic Fibrosis Transmembrane Regulator gene; NM_000492.2) genotyping results were positive for p.E92K; p.F1052V mutations. The patient was diagnosed with cystic fibrosis. In our patient, with features of CF and normal sweat test, mutation analysis was helpful for the diagnosis of cystic fibrosis.