Artemis deficiency: A large cohort including a novel variant with increased radiosensitivity.

BACKGROUND: Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented. METHODS: The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age- and sex-matched healthy control. RESULTS: Seven patients who had severe infections in the first 6 months of life were diagnosed with T-B-NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post-transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12-45) months of follow-up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation. CONCLUSION: Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient's quality of life.

Minipuberty period of children with atopic dermatitis compared to healthy children.

Background/aim: Atopic dermatitis (AD) is an inflammatory, pruritic, noncontagious, chronic relapsing skin disease. Skin barrier abnormalities, excessive T helper 2 activity, and immune dysregulation are held responsible. Androgens have a negative effect on the integrity of the epidermal skin barrier, while estrogen has a positive effect. We aimed to investigate whether hormones make a difference between healthy children and children with AD during minipuberty. Materials and methods: A total of 96 infants (postnatal 4-13 weeks), 48 diagnosed with AD and 48 controls, were included. Each group consisted of 23 girls (47.9%) and 25 boys (52.1%). Anthropometric examinations and hormone measurements were compared. Results: The two groups, having similar age, sex, body mass index, and weight-for-length standard deviation scores, were compared. Serum free thyroxine (FT4) levels were found to be lower and insulin-like growth factor binding protein-3 (IGFBP3) levels were found to be higher in children with AD (p < 0.001 and p = 0.038, respectively). In girls with AD, estradiol, FT4, and insulin-like growth factor-1 (IGF-1) levels were found to be lower, but thyroid-stimulating hormone (TSH) levels were found to be higher (p = 0.023, p < 0.001, p = 0.038, and p = 0.034, respectively). In boys with AD, the FT4 level was found to be lower (p = 0.023). Serum FT4 and TSH levels were within normal reference ranges in all comparisons. Conclusion: Especially in girls with AD, decreased estradiol and IGF-1 levels were observed compared to the controls during minipuberty. In the logistic regression model, decreased levels of serum estradiol, dehydroepiandrosterone sulfate, FT4, and IGF-1, and increased levels of IGFBP3 were associated with an increased likelihood of exhibiting atopic dermatitis.

Serum sRAGE levels in children with atopic dermatitis: a prospective study.

Introduction: Atopic dermatitis (AD) is chronic inflammatory skin disorder. The receptor for advanced glycation end products (RAGE) plays a role in inflammatory reactions. The soluble form of RAGE (sRAGE) acts as a decoy to inhibit interactions of RAGE. Aim: To determine serum sRAGE levels in children with AD. Material and methods: AD diagnosis was made according to Hanifin and Rajka criteria. Disease severity was scored by the scoring atopic dermatitis (SCORAD) index. Skin prick testing (SPT), total immunoglobulin E (Ig E) and eosinophil counts were analysed. The sRAGE levels were determined using ELISA technique. Results: The children, aged 0.4 to 2.0 years with AD (n = 65) were investigated in two groups according to the presence (AD+/Atopy+ [n = 40]) or absence (AD+/Atopy- [n = 25]) of SPT positivity. The comparisons were made with a healthy control group matched for age and sex. The medians (interquartile range) of sRAGE levels in patient and control groups were 8.43 (1.04-18.37) and 14.09 (6.35-28.64), respectively (p < 0.001). The medians (interquartile range) of sRAGE levels in AD+/Atopy+, AD+/Atopy- and control groups were 8.5 (3.1-17.27), 7.75 (1.04-18.37) and 14.09 (6.35-28.64), respectively (p = 0.004). Correlation analysis failed to reach significance with the disease severity sRAGE levels, total IgE levels and eosinophil counts. Conclusions: To our knowledge, this is the first study investigating the association of sRAGE levels with AD and disease severity in childhood. Serum sRAGE levels are decreased in AD but not correlated with disease severity. sRAGE levels may be important in the AD disease process.

The plasma gelsolin levels in atopic dermatitis: Effect of atopy ad disease severity

BACKGROUND: Gelsolin is an actin-binding protein with several cellular functions including anti-apoptosis and is reported to have an anti-inflammatory effect. Apoptosis of keratinocytes has been implicated as a key mechanism of atopic dermatitis (AD). OBJECTIVE: We aimed to determine plasma gelsolin (pGSN) levels in children with atopic dermatitis (AD). METHOD: The diagnosis of AD was made according to Hanifin and Rajka criteria. The disease severity was scored by objective SCORAD index by the same allergist. Skin prick testing (SPT), total IgE levels, and eosinophil counts were analyzed. The pGSN levels were determined using ELISA technique. RESULTS: Children aged between 0.5 and 3.0 years were included in the study. The children with AD (AD; n = 84) were analyzed in two groups according to the presence (AD+/Atopy+; n = 54) or absence of SPT positivity (AD+/Atopy−; n = 30). The comparisons were made with a healthy control group matched for age and sex (n = 81). The median (interquartile range) of pGSN levels in AD+/A+, AD+/A− and control groups were 267 μg/ml (236-368), 293 (240-498) and 547 (361-695), respectively (p < 0.001). The difference between the control group and AD sub-groups remained significant after Bonferroni correction (p < 0.001). Correlation analysis failed to reach significance with the disease severity total IgE levels and eosinophil counts. CONCLUSION: This is the first study investigating the association of pGSN levels with AD and disease severity. pGSN levels decreased in AD. These findings suggest that gelsolin may have a role in the disease process in AD patients

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Effect of montelukast on clinical score and cytokine levels of infants for clinically diagnosed acute bronchiolitis

BACKGROUND: Acute bronchiolitis comprises a major cause for morbidity in infants with viral infection which induces an immune inflammatory response that may produce long lasting harmful effects. Currently, there is no effective therapy for bronchiolitis. OBJECTIVE: Our aim was to investigate the efficacy of five-day montelukast therapy in acute bronchiolitis management. METHODS: The study included 50 infants with acute bronchiolitis. The infants with first episode of acute bronchiolitis were randomly assigned to receive daily montelukast dose of 4 mg over five days after admission or no treatment. Plasma eotaxin, IL-4, IL-8 and IFN-gamma levels were evaluated before and after treatment by ELISA method. In the present study, the primary outcome measure was change in clinical severity score, whilst secondary outcome measures were changes in plasma eotaxin, IL-4, IL-8, IFN-gamma levels. RESULTS: No significant differences was found in clinical severity score with five-day montelukast treatment (p > 0.05, Mann-Whitney U test). There were no significant differences in plasma eotaxin, IL-4, IL-8, IFN-gamma levels between the groups (p > 0.05 Mann-Whitney U test). There was significant decrease in plasma IFN-gamma levels following five-day montelukast treatment (p = 0.027, Wilcoxon). There were no significant differences in plasma IL-4, IL-8, IFN-gamma levels between the groups after five-day montelukast treatment (p > 0.05, Wilcoxon). There was significant increase in eotaxin levels after five-day montelukast treatment (p = 0.009, Wilcoxon). CONCLUSION: Our study showed that montelukast affected plasma IFN-gamma and eotaxin levels after five days of treatment. Further studies are needed to demonstrate effects of montelukast on chemokine levels in bronchiolitis

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