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D vitaminin aşırı kullanılmasının potansiyel yan etkileri iyi bilinmektedir. D-vitaminin aşırı kullanılımı barsaktan kalsiyum emilimini artırıp hiperkalsemi ve hiperkalsiüriye; bu ise nefrokalsinozis, ürolitiyazis ve yumuşak dokuda kalsifikasyonlara yol açabilir. Farklı radyolojik bulguları olan üç iyatrojenik D-vitamini intoksikasyonu olgusunun klinik özellikleri sunulmuştur. D vitamini intoksikasyonundan ve komplikasyonlarından kaçınılması için D-vitamini dozu dikkatli hesaplanmalıdır. Ayrıca, çocuklar için zararlı olabilecek ilaçların reçetesiz satılması engellenmelidir.

Annual Meeting of the Clinical-Immunology-Society (CIS) / Immune Deficiency and Dysregulation North American Conference -- APR 04-07, 2019 -- Atlanta, GA, WOS: 000463709600246, Clathrin-mediated endocytosis (CME) is the major endocytic pathway by which eukaryotic cells internalize cell-surface cargo proteins and extracellular molecules, thereby allowing for a broad range of biological processes, including cell signaling, nutrient and growth factor uptake, and cell fate and differentiation1. The FBAR domain only proteins 1 and 2 (FCHO1/FCHO2) are involved in the initiation of clathrin coat pit formation. Whether FCHO1 and FCHO2 are functionally redundant or have distinct functions is unclear. We report here the first cases of a severe immunodeficiency due to a genetic defect affecting CME. By using whole exome sequencing and genomic analysis of a targeted PID gene panel, we have identified biallelic loss-of-function FCHO1 mutations in five patients from unrelated families of Italian (P1), Turkish (P2, P3, and P5) and Algerian (P4) origin with severe T cell lymphopenia manifesting as recurrent and severe infections of bacterial, mycobacterial, viral and fungal origin. P3 developed EBV-associated diffuse large B cell lymphoma. Three patients (P3-P5) died in childhood, whereas P1 and P2 are alive with full donor chimerism at 13 and 1.5 years after allogeneic hematopoietic stem cell transplantation, respectively and have cleared pre-transplant infections. Patients P2, P3, and P4 carried homozygous frameshift mutations predicted to cause premature termination. Western-blotting analysis of HA- or FLAG-tagged FCHO1 constructs showed expression of truncated products in P2 and P3, whereas no protein was detected in P4, presumably due to mRNA decay. P1 and P5 carried homozygous splice-site mutations at the invariant -1 and +1 positions, respectively, leading to skipping of exon 6 in P1's FCHO1 cDNA. qPCR analysis demonstrated differential expression of the FCHO1 and FCHO2 genes, with the former being predominantly expressed in lymphoid cells, whereas FCHO2 was more abundantly expressed in fibroblasts and K562 cells. Analysis of T cell activation in P2 (the only patient for whom pre-transplant PBMC were available) revealed reduced T cell proliferation. While TCR internalization in response to CD3 cross-linking was normal (consistent with recent evidence that TCR internalization occurs through a clathrin-independent pathway), chase experiments demonstrated that transferrin internalization was abolished in activated T cells from P2. We had previously reported that a missense mutation in TFRC, encoding transferrin receptor 1, impairs transferrin internalization and intracellular iron delivery, causing a combined immunodeficiency with defective T cell proliferation. Our data identify the first form of severe immunodeficiency due to defects of clathrin-mediated endocytosis, and provide additional evidence in support of the critical role played by iron cellular metabolism in T cell function and homeostasis., Clin Immunol Soc

WOS: 000465264700008, PubMed: 30997788, Background/aim: The serum immunoglobulin levels are used routinely in clinical practice because they provide key information on the humoral immune status. This study aimed to determine the age-related reference values of serum immunoglobulin levels in healthy children. Materials and methods: A total of 330 healthy children, aged between 0 and 18 years, were included in this study. The serum immunoglobulin levels were measured using a nephelometric method in a total of 11 groups, each group consisting of 30 individuals, and IgG subclasses in 6 groups of children aged more than 2 years. Results: The serum IgG levels were high during the newborn period, decreased until the sixth month, and again increased to a maximum level at the age of 18 years. The level of IgA was found to be extremely low in the newborn period and then increased with age. While the lowest value was in the newborn period for serum IgM level, the highest value was in the 16- to 18-year-old period. The IgG subclasses varied depending on the age groups. Conclusion: The updated reference intervals of immunoglobulin levels in children may be used for the accurate diagnosis of immune deficiencies., Scientific Research Projects of Selcuk UniversitySelcuk University [15102034], We thank the children and their families for participating. The study was supported by the Scientific Research Projects of Selcuk University (Project No: 15102034).

Background Genetic deficiencies of immune system, referred to as inborn errors of immunity (IEI), serve as a valuable model to study human immune responses. In a multicenter prospective cohort, we evaluated the outcome of SARS‐CoV‐2 infection among IEI subjects and analyzed genetic and immune characteristics that determine adverse COVID‐19 outcomes. Methods We studied 34 IEI patients (19M/15F, 12 [min: 0.6‐max: 43] years) from six centers. We diagnosed COVID‐19 infection by finding a positive SARS‐CoV‐2 PCR test (n = 25) and/or a lung tomography scoring (CORADS) ≥4 (n = 9). We recorded clinical and laboratory findings prospectively, fitted survival curves, and calculated fatality rates for the entire group and each IEI subclass. Results Nineteen patients had combined immune deficiency (CID), six with predominantly antibody deficiency (PAD), six immune dysregulation (ID), two innate immune defects, and one in the autoinflammatory class. Overall, 23.5% of cases died, with disproportionate fatality rates among different IEI categories. PAD group had a relatively favorable outcome at any age, but CIDs and IDs were particularly vulnerable. At admission, presence of dyspnea was an independent risk for COVID‐related death (OR: 2.630, 95% CI; 1.198–5.776, p, 34 IEI patients aged between 0.6 and 43 years, eight patients (23.5%) succumbed to COVID‐19, indicating a highly vulnerable condition to COVID‐19. Laboratory markers associated with mortality included elevated acute phase reactants, ferritin, troponin T, TLS, and reduced ALC levels, albumin, and baseline IgG. Coughing, dyspnea, CORADS category 4–6, and negative SARS‐CoV‐2 PCR at admission were among the predictors of lethal outcome.

WOS: 000495942300001, PubMed: 31713830, …

WOS: 000480413700005, Objective: Periostin, an extracellular matrix protein, is related to the eosinophilic airway inflammation. There is no specific marker in allergen immunotherapy to evaluate clinical response. We aimed to investigate the serum periostin levels in the children who receive allergen immunotherapy. Materials and Methods: Sixteen patients between 8-18 years (12.7 +/- 2.8 years) with allergic rhinitis and/or asthma due to grass pollen hypersensitivity and 30 healthy subjects (11.7 +/- 2.6 years) were included. Demographic data, eosinophil counts, skin prick tests and the specific IgE levels of the patients are recorded. Symptom scores, visual analog scales, medication scores were determined and the serum periostin levels were measured in the beginning, 4th and 12th months of the allergen immunotherapy. Results: The symptom scores for rhinitis in the 4th month showed significant improvements in all of the patients (p< 0.05). Nine patients with allergic rhinitis accompanied by asthma, showed significant improvements in 12th month symptom score for asthma (p=0.018). A significant correlation was detected between the initial serum periostin levels and the symptom scores for the eye (r=0.668, p=0.005). No significant difference was found in serum periostin levels between the patient and the control groups. There were no significant differences in serum periostin levels in 4th and 12th months compared to the ones in the beginning. Conclusion: In this study, there were no significant differences in serum periostin levels of children during the allergen immunotherapy. The association of serum periostin levels with symptom scores for the eye needs to be confirmed in more children with allergic rhinoconjunctivitis.

WOS: 000470113200044, PubMed: 30822429, …, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; "Angelo Nocivelli'' Foundation, Supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, and by the "Angelo Nocivelli'' Foundation.

WOS: 000268860400023, PubMed ID: 19577286, Background: The hyper IgE syndrome (HIES) is characterized by abscesses, eczema, recurrent infections, skeletal and connective tissue abnormalities, elevated serum IgE, and diminished inflammatory responses. It exists as autosomal-dominant and autosomal-recessive forms that manifest common and distinguishing clinical features. A majority of those with autosomal-dominant HIES have heterozygous mutations in signal transducer and activator of transcription (STAT)-3 and impaired T(H)17 differentiation. Objective: To elucidate mechanisms underlying different forms of HIES. Methods: A cohort of 25 Turkish children diagnosed with HIES were examined for STAT3 mutations by DNA sequencing. Activation of STAT3 by IL-6 and IL-21 and STAT1 by IFN-alpha was assessed by intracellular staining with anti-phospho (p)STAT3 and -pSTAT1 antibodies. T(H)17 and T(H)1 cell differentiation was assessed by measuring the production of IL-17 and IFN-gamma, respectively. Results: Six subjects had STAT3 mutations affecting the DNA binding, Src homology 2, and transactivation domains, including 3 novel ones. Mutation-positive but not mutation-negative subjects with HIES exhibited reduced phosphorylation of STAT3 in response to cytokine stimulation, whereas pSTAT1 activation was unaffected. Both patient groups exhibited impaired TH17 responses, but whereas STAT3 mutations abrogated early steps in TH17 differentiation, the defects in patients with HIES with normal STAT3 affected more distal steps. Conclusion: In this cohort of Turkish children with HIES, a majority had normal STAT3, implicating other targets in disease pathogenesis. Impaired TH17 responses were evident irrespective of the STAT3 mutation status, indicating that different genetic forms of HIES share a common functional outcome. (J Allergy Clin Immunol 2009;124:342-8.), National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [5R01AI065617], Supported by National Institutes of Health grant 5R01AI065617 (T.C.).