Therapeutic modalities and clinical outcomes in a large cohort with LRBA deficiency and CTLA4 insufficiency.

BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency (LRBA-/-) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) insufficiency (CTLA4+/-) are mechanistically overlapped diseases presenting with recurrent infections and autoimmunity. The effectiveness of different treatment regimens remains unknown. OBJECTIVE: Our aim was to determine the comparative efficacy and long-term outcome of therapy with immunosuppressants, CTLA4-immunoglobulin (abatacept), and hematopoietic stem cell transplantation (HSCT) in a single-country multicenter cohort of 98 patients with a 5-year median follow-up. METHODS: The 98 patients (63 LRBA-/- and 35 CTLA4+/-) were followed and evaluated at baseline and every 6 months for clinical manifestations and response to the respective therapies. RESULTS: The LRBA-/- patients exhibited a more severe disease course than did the CTLA4+/- patients, requiring more immunosuppressants, abatacept, and HSCT to control their symptoms. Among the 58 patients who received abatacept as either a primary or rescue therapy, sustained complete control was achieved in 46 (79.3%) without severe side effects. In contrast, most patients who received immunosuppressants as primary therapy (n = 61) showed either partial or no disease control (72.1%), necessitating additional immunosuppressants, abatacept, or transplantation. Patients with partial or no response to abatacept (n = 12) had longer disease activity before abatacept therapy, with higher organ involvement and poorer disease outcomes than those with a complete response. HSCT was performed in 14 LRBA-/- patients; 9 patients (64.2%) showed complete remission, and 3 (21.3%) continued to receive immunosuppressants after transplantation. HSCT and abatacept therapy gave rise to similar probabilities of survival. CONCLUSIONS: Abatacept is superior to immunosuppressants in controlling disease manifestations over the long term, especially when started early, and it may provide a safe and effective therapeutic alternative to transplantation.

Incidental pulmonary nodules in children: characteristic features and clinical course.

BACKGROUND: There exists insufficient information about the natural course of incidental pulmonary nodules (IPN) determined on tomography in children. The aim was to determine the characteristic features and factors affecting the course of IPN. METHODS: This retrospective study included patients who presented at the Pediatric Pulmonology, Allergy & Immunology Section of Akdeniz University Hospital between January 2014-2020, and were determined with pulmonary nodules on high-resolution computed tomography (HRCT). The patients were separated into two groups as those with a nodule decreased in size or which had disappeared on the follow-up HRCT (Group 1) and those with a nodule which had remained at the same size (Group 2). These two groups were compared in respect to demographic data, nodule size and characteristics, and accompanying findings on HRCT. RESULTS: A total of 177 nodules were determined in the 66 patients included in the study. A follow-up HRCT was taken within mean 16.29±11.38 months in 27 patients. In these patients, 78 nodules were determined on the initial HRCT. On the follow-up, twelve of the nodules were seen to have shrunk or disappeared compared to the initial images, 66 had remained the same size, and none had grown. The mean age of the patients in Group 1 was statistically significantly lower than that of patients in Group 2 (p < 0.001). The rates of an accompanying mosaic attenuation pattern (p < 0.001) on HRCT and subsolid density (p=0.011) of the nodules in Group 1 were statistically significantly higher compared to Group 2 and the rate of calcification content was statistically significantly lower (p=0.002). No suspicious or confirmed malignancy was observed in any case throughout the mean follow-up period of 38.33±16.5 months after the initial HRCT. CONCLUSIONS: The young age of patients, subsolid structure of nodules, calcification content and the presence of an accompanying mosaic attenuation pattern on HRCT, could be useful factors in the estimation of size in the follow-up of nodules.

Psychological State of Parents of Children with Primary Immunodeficiencies During the COVID-19 Pandemic.

Background: COVID-19 has affected humanity not only physically but also mentally. It was expected to have impact on high-risk groups such as the immunocompromised patients and parents/caregivers of them. Our study was aimed to investigate the COVID-19 related anxiety, post-traumatic stress levels, and sleep-related parameters of the parents of children with primary immunodeficiency. Methods: Parents of children with primary immunodeficiency and age and gender-matched control group completed questionnaires. Results: Anxiety and post-traumatic stress levels of the study group were found to be significantly higher than the control group. Furthermore, sleep time of the study group was significantly lower than the control group. The subjective sleep quality of the study group was also lower in the study group, but the difference did not reach a significant level. Conclusions: In the ongoing and other possible pandemic processes, professional support for the parents of these children is of great importance.

Specific Granule Deficiency Due To Novel Homozygote SMARCD2 Variant.

Background: Specific granule deficiency (SGD) is a rare immunodeficiency associated with CCAT/enhancer-binding protein epsilon (CEBPE) gene variants. It can cause severe recurrent infections and is lethal without successful stem cell transplantation. Few cases with SGD of both type 1 and type 2 have been described in the literature. In this study, we present the first report of a case with a novel homozygous c.511 C > T (p.Gln171Ter) mutation in the SMARCD2 gene of SGD type 2, which was successfully treated with bone marrow transplantation. Case: A male infant presented to our neonatal intensive care unit on the second day of life with an icteric appearance and mild hypotonia. He was evaluated for immunodeficiency as the cause of delayed cord separation and refractory neutropenia. At 6 weeks of age, SGD type 2 with a new variant was diagnosed and successfully treated by bone marrow transplantation. Conclusion: SGD is an immunodeficiency disease that is quite rare. However, we believe that SGD diagnosis and associated new variants can be detected more frequently with the widespread use of all whole-exome sequencing techniques.

Association Between Cystic Fibrosis Severity Markers and CFTR Genotypes in Turkish Children.

OBJECTIVE: To compare class I/II cystic fibrosis transmembrane conductance regulator (CFTR) mutations to class III-V mutations with regards to cystic fibrosis disease severity markers in children. MATERIAL AND METHODS: This study was designed as a cross-sectional study in Antalya province, located on the south coast of Turkey. The study included 38 cystic fibrosis patients aged between 0.6 and 18 years. The CFTR genotype of the patients was categorized into 2 groups based on the presence or absence of class I or class II mutations in any of the alleles. Group I comprised 8 homozygous, 8 with unknown alleles, and 8 compound heterozygous patients, and group II comprised 11 homozygous and 3 compound heterozygous patients. The groups were analyzed in respect of cystic fibrosis disease severity markers, such as spirometry, ShwachmanKulczycki score, body mass index (BMI), sweat chloride concentration, chronic Pseudomonas aeruginosa infection, annual exacerbation frequency, and severe exacerbations requiring hospitalization during the previous year. RESULTS: In the comparison of group I and group II patients, a significant difference was observed in pancreas insufficiency (83.3% vs. 35.7%; P = .005), chronic P. aeruginosa infection (58.3% vs. 7.1%; P = .002), cough severity score (1.7 ± 1.1 vs. 0.9 ± 1.5; P = .029), number of severe exacerbations requiring hospitalization during the previous year (0.9 ± 1 vs. 0.3 ± 0.8; P = .03), and sweat chloride levels (76.7 ± 15.2 vs. 61 ± 22.3; P = .02). All these values were higher in group I patients. The mean BMI values (15.8 ± 2.2 vs. 17.6 ± 2.8; P = .03) were lower in group I patients. CONCLUSION: There seems to be a difference between class I/II CFTR mutations and class III-V mutations on the severity of the disease in cystic fibrosis patients.

An evaluation of banana allergy in children living in the Mediterranean region

Background/aim: We aimed to apply a double-blind placebo-controlled food challenge (DBPCFC) test to patients who reported a reaction to banana and showed positivity for banana-specific IgE in Turkey. Materials and methods: Medical data of patients who had been analyzed for banana allergy were reviewed, focusing on banana-specific IgE positivity at the Department of Pediatric Allergy-Immunology at the Akdeniz University Faculty of Medicine between the years 2004 and 2012. Patients were called to the clinic for a DBPCFC test. Results: A total of 47 patients participated. We determined reactions in 13% of DBPCFC patients. A cut-off value was determined as 0.66 kU/L for banana-specific IgE, and sensitivity and specificity were 83% and 51%, respectively. The positive predictive value for specific IgE was 20% while the negative predictive value was 96%. Sensitivity and specificity for banana prick-to-prick test (P + P) was 33% and 93%, respectively; positive predictive value was 40% and negative predictive value was 91%. Conclusion: This is the first study conducted in Turkey to use a DBPCFC test in the diagnosis of banana allergy. Up until now, the positive predictive value was not defined for banana-specific IgE. Our study showed that specific IgE or skin tests alone are not adequate for the diagnosis of food allergy; to define subjective symptoms related to food and to determine cross-reactions, DBPCFC tests should be done for confirmation.