[Analysis of IFN-γR1 (CD119) and IL-12Rß1 (CD212) Deficiency by Flow Cytometry]. / IFN-γR1 (CD119) ve IL-12Rß1 (CD212) Eksikliginin Akan Hücre Ölçer ile Analizi.

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare primary immune deficiency (PID). IL-12Rß1 deficiency is the most frequently observed of more than 16 genetic defects that have been identified for MSMD. Genetic and immunological tests are remarkable in the diagnosis of PID. In this study, it was aimed to determine the expression of IFN-γR1 and IL-12Rß1 in patients with MSMD, their relatives, and healthy individuals and to evaluate the importance of flow cytometry as a fast and reliable method in the diagnosis of MSMD. IFN-γR1 and IL-12Rß1 expression levels were analyzed in 32 volunteers including six patients, six relatives, and 20 healthy individuals. The normal range of IFN-γR1 and IL-12Rß1 levels among healthy individuals were determined. IL-12Rß1 expression level in lymphocytes was found to be low in one patient's relative, and less than 1% in three patients and in one patient's relative. It was observed that the IL-12Rß1 expression levels of the patient with STAT1 deficiency were increased compared to the healthy individuals. No difference was found in the expression levels of IFN-γR1 and IL-12Rß1 in one patient, but IFN-γR1 expression was decreased in one patient compared to healthy individuals. Our results show that the determination of IL-12Rß1 and IFN-γR1 deficiencies by flow cytometry can be used as a rapid and reliable method for the diagnosis of MSMD. The use of this method as a screening test will enable early diagnosis especially in patients whose genetic diagnosis has not been confirmed and clinically compatible with MSMD. In addition, it is thought that IL-12Rß1 and IFN-γR1 range data obtained from healthy individuals will be considered as a reference source in routine and research studies to be conducted with MSMD.

A case of severe DRESS syndrome treated with therapeutic plasma exchange and intravenous immunoglobulin therapy.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in children is a rare adverse drug reaction with skin rash, fever, hematologic abnormalities, and multiorgan involvement. The diagnosis is difficult because of its various clinical presentations, nonetheless is extremely important due to the mortality rate. We describe a 14-year-old boy who developed hypersensitivity to either teicoplanin or meropenem therapy. After failing to improve with corticosteroids, he was successfully treated with therapeutic plasma exchange (TPE). TPE should be considered in the treatment with corticosteroid-resistant DRESS syndrome.

Altered immune response in organic acidemia.

BACKGROUND: Most patients with organic acidemia suffer from recurrent infections. Although neutropenia has been reported in multiple studies, other components of the immune system have not been evaluated thoroughly. This study was conducted to assess the immune status of patients with organic acidemia (OA). METHODS: Thirty-three patients with OA who were followed up in Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Nutrition and Metabolism Department and a total of 32 age- and sex-matched healthy controls were enrolled to the study. The demographic and clinical data were recorded retrospectively from patient files. Complete blood counts, immunoglobulins, and lymphocyte immunophenotyping were recorded prospectively in a symptom- (infection-) free period. RESULTS: Of the 33 patients enrolled to the study, 21 (88%) were diagnosed with methylmalonic acidemia, 10 (33%) with propionic acidemia, and two (6.6%) with isovaleric acidemia. The mean age of the patients with OA and healthy subjects were 5.89 ± 4.11 years and 5.34 ± 4.36, respectively (P = 0.602). Twenty-nine (88%) of the patients had experienced frequent hospital admission, 13 (39%) were admitted to pediatric intensive care unit, and 18 (55%) suffered from sepsis. Naïve helper T cells and recent thymic emigrants were significantly lower in OAs (P < 0.001). Various defects in humoral immunity have also been documented including memory B cells and immunoglobulins. CONCLUSIONS: Patients with OAs may show adaptive immune defects rendering them susceptible to infections. Metabolic reprogramming based on nutritional modifications may be a promising therapeutic option in the future.

COmparisoN of TastES of Available NutriTional integrated or non-integrated formulas for infants older than 1 year of age with cow's milk allergy: A multicenter, prospective, single blind, cross-sectional observational clinical study (CONTEST Study).

Palatability of the infant formulas lacking cow milk protein formulas is reported by parents to be an important drawback. The purpose of this study is to examine decisions made by mothers of infants having cow milk protein allergy, and physicians concerning the palatability of unflavored extensively hydrolyzed formulas and amino acid-based formulas. We conducted a multi-center, randomized, single-blinded, observational taste study involving 149 pediatricians from gastroenterology and allergy subspecialties at 14 tertiary healthcare units from different regions of Turkey and involving 94 mothers of infants with cow milk protein allergy. Blinding was performed for seven formulas available in the market, which were the most commonly prescribed for feeding: four AAFs (Neocate-Numil®, Aptamil Pregomin AS-Numil®, Alfamino-Nestle®, Comidagen-Mamma®), one AAF specifically designed to address the growing nutritional and lifestyle needs of children >1 year (Neocate Junior-Numil®), 2 eHFs (Bebelac Pepti Junior-Numil®, Similac Alimentum-Abott®). Considering all three formula characteristics, Neocate junior-Numil® ranked as the number 1 product among seven products by mothers (63.8%) and physicians (69.8%). The ratings of mothers were significantly higher than the physicians (8.1 points and 6.1 points, respectively; p < 0.001). No difference was found in terms of taste, smell, and appearance for Neocate junior-Numil® between the mothers' and physicians' ratings. Since caregivers have responsibility for careful selection of replacement products for infants with cow milk protein allergy, it is noteworthy that increased awareness and confidence in the palatability characteristics of these products should motivate mothers and physicians to comply with replacement treatment in the long term.

Decreased frequency of allergy in juvenile idiopathic arthritis: Results of a case-control study.

OBJECTIVES: To determine the frequency of Th2-mediated allergic diseases (AD) in mainly Th1-driven juvenile idiopathic arthritis (JIA) subtypes. METHODS: Ninety-nine JIA patients and 128 control subjects were enrolled in a prospective case-control study. All subjects were assessed with standard allergy questionnaire, complete blood cell count, and total serum immunoglobulin (sIg) E. sIgs G, A, M, Juvenile Arthritis Disease Activity Score-27 (JADAS27), and serum acute phase reactants (sAPR) were obtained in JIA. In the presence of allergic symptoms, skin prick (SPT) and pulmonary function tests (PFT) were performed. RESULTS: Despite similar allergy risk factors, the frequencies of asthma and allergic rhinitis were lower in JIA group (all p ≤ .02). Allergic patients with JIA performed lower FEV1/FVC ratio, PEF, and FEF25-75 compared to the control group (all p ≤ .04). JADAS27 and sAPR were similar among JIA patients with and without AD. Two JIA patients were found to have hypogammaglobulinemia. CONCLUSION: The frequencies of AD, asthma, and allergic rhinitis may decrease in Th1-mediated JIA subtypes although the coexistence does not appear to affect the severity of arthritis whereas allergic symptoms may resolve after immunosuppressive treatment. PFTs should be obtained periodically in JIA. JIA patients may have an underlying primary immunodeficiency (ID) or immunosuppressive drugs may cause secondary ID.KEY POINTSCompared to the population, the frequency of Th2-mediated allergic diseases is lower in oligoarthritis and RF-negative polyarthritis that are primarily driven by a Th1 activity.The coexistence of allergic diseases in juvenile idiopathic arthritis does not affect the severity of arthritis.Pulmonary function tests can be thought to be obtained periodically in juvenile idiopathic arthritis.Immunological workup should be considered in atypically or severely presented patients with juvenile idiopathic arthritis before the initiation of immunosuppressive therapy to differentiate primary and secondary immunodeficiency.

Sleep, executive functions, and functional impairment in children with specific learning disorder: An investigation of the mediating pathways.

OBJECTIVE: Sleep problems and executive dysfunction are associated with functional impairment in children with neurodevelopmental disorders. In this study, we aimed to investigate these aspects in children with Specific Learning Disorders (SLD) and SLD with comorbid Attention-Deficit Hyperactivity Disorder (ADHD), while also evaluating differences with typically developing (TD) children. Our study hypothesizes that children with SLD, especially those with comorbid ADHD, face greater sleep disturbances and executive function challenges compared to TD peers. We also propose that sleep disturbances aggravate functional impairment and that executive functions mediate this relationship. METHOD: The data obtained from psychiatric evaluations, semi-structured interviews and questionnaires filled out by parents were analyzed. RESULTS: SLD + ADHD group had worse scores in all scales, followed by SLD and TD groups. Mediator analysis demonstrated that executive functions had a mediator role in the relationship between sleep problems and functional impairment. CONCLUSION: Our findings suggest that children with SLD experience more significant difficulties in daily living than their typically developing peers and having ADHD comorbidity, poor executive functions, and additional sleep problems can further exacerbate impairment. Notably, our mediation analysis suggests that executive functions mediate the relationship between sleep disturbances and the severity of functional impairments.

Comparisons of Clinical Features and Outcomes of COVID-19 between Patients with Pediatric Onset Inflammatory Rheumatic Diseases and Healthy Children.

(1) Background: We aimed to describe the clinical features and outcomes of coronavirus disease-2019 (COVID-19) in children and late adolescents with inflammatory rheumatic diseases (IRD) and to measure their severity risks by comparing them with healthy children. (2) Methods: Among children and late adolescents found to be severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) positive via polymerase chain reaction (PCR) test, IRD patients with an at least six-months follow-up duration, and healthy children were included in the study. Data were obtained retrospectively. (3) Results: A total of 658 (339 (51.5%) females) (healthy children: 506, IRD patients: 152) subjects were included in the study. While 570 of 658 (86.6%) experienced COVID-19-related symptoms, only 21 (3.19%) required hospitalization with a median duration of 5 (1-30) days. Fever, dry cough, and fatigue were the most common symptoms. None of evaluated subjects died, and all recovered without any significant sequelae. The presence of any IRD was found to increase the risk of both hospitalization (OR: 5.205; 95% CI: 2.003-13.524) and symptomatic infection (OR: 2.579; 95% CI: 1.068-6.228). Furthermore, increasing age was significantly associated with symptomatic infection (OR: 1.051; 95% CI: 1.009-1.095). (4) Conclusions: Our study emphasizes that pediatric rheumatologists should monitor their patients closely for relatively poor COVID-19 outcomes.

The Relationship between Genotype and Phenotype in Primary Ciliary Dyskinesia Patients.

OBJECTIVES: Primary ciliary dyskinesia (PCD) is a chronic genetic disease that affects the respiratory tract, characterized by different clinical and laboratory features. It has a very difficult diagnosis, and high morbidity. In recent years, with the advances in genetics, the rate of diagnosis has increased considerably. In this study, it was aimed to evaluate the relationship between PCD patients' clinical, radiological and laboratory features and genetic analysis. METHODS: The study included 14 children who were diagnosed with PCD between 2015-2019 and underwent exome analysis. Diagnostic ages, body mass indexes (BMI)- Z score, clinical and radiological findings, pulmonary function tests, sputum culture reproduction and gene analysis were evaluated and compared. RESULTS: Six of the patients (43%) were girls and 8 (57%) were boys, and the median age at the time of diagnosis was 9 (min-max: 3-16) years. Genetic analysis revealed pathogenic mutations in DNAH5 (n=4, 29%), DNAH11 (n=2, 14%), RSPH4A (n=2, 14%), CCDC40 (n=2, 14%), DNAH9 (n=1, 7%), HYDIN (n=1, 7%), DNAH1 (n=1, 7%), and ARMC4 (n=1, 7%). Although not statistically significant, it was found that the diagnosis age was lower and the BMI Z-score was lower in CCDC40 mutations. Growth parametres were normal in DNAH5, DNAH11, RSPH4A and ARMC4 pathogenic variants. No significant correlation was found between genetic analysis and clinical features, culture reproduction and pulmonary function tests of the patients. CONCLUSION: It is thought that more detailed information about the possible clinical features and prognosis of the disease can be obtained by genetic examinations of PCD. However, clinical trials with higher patient numbers are still needed.