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Abstract: Junctional epidermolysis bullosa (JEB) is a rare, incurable, devastating, and mostly fatal congenital genetic disorder characterized by painful blistering of the skin and mucous membranes in response to minor trauma or pressure. JEB is classified roughly into 2 subtypes: JEB-Herlitz is caused by mutations on genes encoding laminin-332. The authors present a patient consulted with a suspicion of primary immunodeficiency due to skin sores that started at the age of 1 month and a history of 3 siblings who died with similar sores, who was diagnosed with JEB-Herlitz after detecting a homozygous LAMC2 gene mutation in WES analysis. Microscopic evaluation of hematoxylin and eosin-stained sections showed vesicle formation with subepidermal separation, which is accompanied by striking neutrophil and eosinophil leukocyte infiltration both in the vesicle and papillary dermis (eosinophil-rich inflammatory infiltrate). Such a histopathological finding has been rarely reported in this condition., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The monogenic causes of very-early-onset inflammatory bowel disease (VEO-IBD) have been defined by genetic studies, which were usually related to primary immunodeficiencies. Receptor-interacting serine/threonine-protein kinase-1 (RIPK1) protein is an important signalling molecule in inflammation and cell death pathways. Its deficiency may lead to various clinical features linked to immunodeficiency and/or inflammation, including IBD. Here, we discuss an infant with malnutrition, VEO-IBD, recurrent infections and polyathritis who has a homozygous partial deletion in RIPK1 gene., (© 2024. The Author(s).)

Background/aim: There are several complications of hematopoietic stem cell transplantation. Without any doubt, most important of these is aGvHD that increases transplant-related mortality. The aim of this study is to investigate whether ST-2 and Reg3α levels measured at an early stage in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation can be individual biomarkers identifying future GvHD and predicting treatment response., Materials and Methods: From January 2019 to January 2021, 27 patients undergoing hematopoietic stem cell transplantation for primary immunodeficiency or hematopoietic diseases formed the study group. During their follow-up, the patients were classified into two groups as those developing and those not developing aGvHD. Nineteen healthy volunteers from a similar age group who needed their blood samples drawn for other reasons and who did not have any history of chronic disease, infection or medication use formed the control group. Blood samples of patients scheduled to have allogeneic HSCT were obtained before the administration of the preparative regimen, on Day +7 post-transplant and on the day of diagnosis if they developed aGvHD. Serum samples were stored at -20ºC until the day of processing. ST2 and Reg3α levels were measured using the ELISA method., Results: For patients who developed aGvHD (n = 13), ST2 levels obtained before the transplantation, on Day +7 post-transplant and on the day of aGvHD diagnosis (in patients developing GvHD) were significantly higher compared to the healthy Control Group (p-value <0.05). As regards to the samples obtained on the same days, ST2 levels did not differ significantly among patients who developed and those who did not develop GvHD (n = 14; p-value >0.05). ST2 levels of samples obtained on the days that acute skin and gastrointestinal tract GvHD developed did not differ significantly between these two groups (p-value >0.05). Reg3α levels of the pre-transplant samples, on Day +7 after the transplantation and on the day of aGvHD diagnosis did not show any difference between any of the groups (p-value >0.05). As only two patients died after transplantation, thus correlation of ST2 and Reg3α levels with transplant-related mortality could not be proven., Conclusion: The results of this study suggest that ST2 and Reg3α levels are neither diagnostic nor prognostic or predictive biomarkers of aGvHD, steroid resistance or transplant-related mortality in pediatric patients. This study can be regarded as a pilot study because of the small patient population; more research involving a larger patient population is required., Competing Interests: Conflicts of interest There are no financial or non-financial competing interests. The authors declare no conflicts of interest relevant to this manuscript., (Copyright © 2024 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Requiring pediatric intensive care unit (PICU) admission relates to high mortality and morbidity in patients who received hematopoietic stem cell transplantation (HSCT). In this study, we aimed to evaluate the indications for PICU admission, treatments, and the determining risk factors for morbidity and mortality in patients who had allogeneic HSCT from various donors., Materials and Methods: In this retrospective study, we enrolled to patients who required the PICU after receiving allogeneic HSCT at our Pediatric Bone Marrow Transplantation Unit between 2005 and 2020. We evaluated to indication to PICU admission, applications, mortality rate, and the determining factors to outcomes., Results: Thirty-three (7%) patients had 47 PICU admissions and 471 patients underwent bone marrow transplantation during 16-year study period. Also, 14 repeated episodes were registered in 9 different patients. The median age of PICU admitted patients was 4 (0.3 to 18) years and 29 (62%) were male. The main reasons for PICU admission were a respiratory failure, sepsis, and neurological event in 20, 8, and 7 patients, respectively. The average length of PICU stay was 14.5 (1 to 80) days, 14 (43%) of patients survived and the mortality rate was 57%. Multiple organ failure ( P =0.001), need for respiratory support ( P =0.007), inotrope agents ( P =0.001), and renal replacement therapy ( P =0.013) were found as significant risk factors for mortality., Conclusions: Allogeneic HSCT recipients need PICU admission because of its related different life-threatening complications. But there is a good chance of survival with quality PICU care and different advanced organ support methods., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Aspirin desensitization (AD) is an effective treatment in patients with non-steroidal anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (NERD) by providing inhibitory effect on symptoms and polyp recurrence. However, limited data is available on how AD works. We aimed to study comprehensively the mechanisms underlying AD by examining basophil activation (CD203c upregulation), mediator-releases of tryptase, CysLT, and LXA 4 , and LTB 4 receptor expression for the first 3 months of AD., Methods: The study was conducted in patients with NERD who underwent AD (group 1: n  = 23), patients with NERD who received no desensitization (group 2: n  = 22), and healthy volunteers (group 3, n  = 13). All participants provided blood samples for flow cytometry studies (CD203c and LTB 4 receptor), and mediator releases (CysLT, LXA 4, and tryptase) for the relevant time points determined., Results: All baseline parameters of CD203c and LTB 4 receptor expressions, tryptase, CysLT, and LXA 4 releases were similar in each group ( p  > 0.05). In group 1, CD203c started to be upregulated at the time of reactions during AD, and continued to be high for 3 months when compared to controls. All other study parameters were comparable with baseline and at the other time points in each group ( p  > 0.05)., Conclusion: Although basophils are active during the first 3 months of AD, no releases of CysLT, tryptase or LXA 4 exist. Therefore, our results suggest that despite active basophils, inhibition of mediators can at least partly explain underlying the mechanism in the first three months of AD.

Invasive aspergillosis (IA) is a major cause of morbidity and mortality. This study aimed to present our 10-year IA experience at a single center. Fifty-nine pediatric patients with IA were included in this study. The male-to-female ratio was 42/17. The median age was 8.75 years. Hematologic malignancy was present in the majority of the patients (40/59, 68%). The mean neutropenia duration was 18.5 days. Cytosine arabinoside was the most common immunosuppressive therapy directed at T cells during IA diagnosis. IA cases were categorized as proven (27%), probable (51%), or possible (22%) according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. The lungs (78%) were the most common site of IA, and nodules were the most frequent radiological findings (75.5%). In 38 patients (64.4%) receiving antifungal prophylaxis, prophylactic agents included fluconazole (30.5%), liposomal amphotericin B (23.7%), posaconazole (8.5%), and voriconazole (1.7%). Initial treatment was most commonly administered as monotherapy (69.5%). The median antifungal treatment duration was 67 days. Eleven deaths (18.6%) were due to aspergillosis. With the increased use of corticosteroids, biological agents, and intensive immunosuppressive chemotherapy, IA will most likely continue to occur frequently in pediatric patients.

Background: Early diagnosis and effective treatment serve as life-saving procedures for primary immunodeficiencies (PIDs) which are very common and a major public health problem in Turkey. Severe combined immunodeficiency (SCID) is constitutively a T-cell defect in which naïve T-cell development is defective due to the mutations in genes responsible for the T cell differentiation and insufficient thymopoiesis. So, assessment of thymopoiesis is very important in the diagnosis of SCID and several combined immune deficiencies (CIDs)., Methods: The purpose of this study is to examine thymopoiesis in healthy children via measurement of recent thymic emigrants (RTE); T lymphocytes that express CD4, CD45RA and CD31 to establish the RTE reference values in Turkish children. RTE were measured in the peripheral blood (PB) of 120 healthy infants and children between 0-6 years including cord blood samples, by flow cytometry., Results: The absolute count of RTE cells and their relative ratios were found to be higher during the first year of life, being highest at the 6th month and tending to decrease significantly by age following birth (p=0.001). In the cord blood group, both values were lower than those in the 6-month-old group. The absolute lymphocyte count (ALC) varying by age, was found to reduce to 1850/mm³ in 4-years and after., Conclusions: Here we evaluated normal thymopoiesis and established the normal reference levels of RTE cells in the peripheral blood of healthy children aged between 0-6 years. We believe that the collected data will contribute to early diagnosis and monitoring of immune reconstitution; serving as an additional fast and reliable marker for many PID patients especially for SCID including many other CIDs, especially in nations where newborn screening (NBS) via T cell receptor excision circles (TREC) has not yet become available.

Background: Invasive aspergillosis (IA) is an important cause of morbidity and mortality in immunosuppressed children. Early detection of the infection can improve prognosis in this patient population., Objectives: To investigate the utility of Aspergillus galactomannan antigen assay (GM-EIA) as a diagnostic tool for IA in at-risk paediatric patients., Patients/methods: For the study, 659 GM-EIA results from 59 patients diagnosed with IA and 3368 GM-EIA results from 351 subjects without evidence for IA (controls) were reviewed retrospectively. Three cut-off values (i.e. ≥0.5, ≥1, ≥1.5) were specified to determine GM-EIA positivity., Results: The median age was 6.3 years for boys and 14.5 years for girls. There was a significant difference between the girls and boys in terms of age ( p  < 0.01). For proven/probable/possible IA patients, sensitivity of 67.8% and specificity of 59.8% were detected when the ≥0.5 cut-off value was used for GM-EIA-positivity. The specificity increased to 80% at the cut-off of ≥1 and to 88% at the cut-off of ≥1.5. False positivity rates were 9.14, 3, and 1.45% at the ≥0.5, ≥1 and ≥1.5 cut-offs respectively. In the proven/probable IA group, sensitivity and negative predictive values were 86.9 and 97.2% at the ≥0.5 cut-off, 85.7 and 97.9%, at the ≥1 cut-off and 84.2 and 98.1% at ≥1.5 cut-off respectively. The positive likelihood ratio was 7.57 and the odds ratio was 42.67 at ≥1.5 cut-off., Conclusion: The GM-EIA may be used for both screening and diagnostic purposes in paediatric patients using a cut-off value of ≥1.5 for GM-EIA positivity.

Objective: Wiskott-Aldrich syndrome (WAS) is an X-linked primary immune deficiency characterized by microthrombocytopenia, eczema, and recurrent infections. We aimed to evaluate the clinical features and outcomes of a WAS cohort., Materials and Methods: We retrospectively evaluated the clinical courses, immunological features, treatments, and outcomes in a total of 23 WAS patients together with data related to 11 transplanted cases among them between 1982 and 2019., Results: Before admission, 11 patients (48%) were misdiagnosed with immune thrombocytopenia. WAS scores were mostly 4 or 5. Eleven patients were transplanted and they had an overall survival rate of 100% during a median follow-up period of 8.5 years (range: 8 months to 20 years). Five patients who were not transplanted died at a median of 7 years (range: 2-26 years). Nontransplanted patients had high morbidity due to organ damage, mostly caused by autoimmunity, bleeding, and infections. Two novel mutations were also defined., Conclusion: All male babies with microthrombocytopenia should be evaluated for WAS. Hematopoietic stem cell transplantation should be performed at the earliest age with the best possible donors.

Pneumonia is a significant cause of death for children, particularly those in developing countries. The records of children who were hospitalized because of pneumonia between January 2003 and December 2015 were retrospectively reviewed, and patients who met the recurrent pneumonia criteria were included in this study. During this 13-year period, 1395 patients were hospitalized with pneumonia; of these, 129 (9.2%) met the criteria for recurrent pneumonia. Underlying diseases were detected in 95 (73.6%) patients, with aspiration syndrome (21.7%) being the most common. Rhinovirus (30.5%), adenovirus (17.2%) and respiratory syncytial virus (13.9%) were the most frequent infectious agents. These results demonstrate that underlying diseases can cause recurrent pneumonia in children. Viruses are also commonly seen in recurrent pneumonia. Appropriate treatments should be chosen based on an analysis of the underlying disease, the patient's clinical condition and the laboratory and radiological data., (© The Author(s) [2018]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Biallelic variations in the dedicator of cytokinesis 8 (DOCK8) gene cause a combined immunodeficiency with eczema, recurrent bacterial and viral infections, and malignancy. Natural disease outcome is dismal, but allogeneic hematopoietic stem cell transplantation (HSCT) can cure the disease., Objective: To determine outcome of HSCT for DOCK8 deficiency and define possible outcome variables., Methods: We performed a retrospective study of the results of HSCT in a large international cohort of DOCK8-deficient patients., Results: We identified 81 patients from 22 centers transplanted at a median age of 9.7 years (range, 0.7-27.2 years) between 1995 and 2015. After median follow-up of 26 months (range, 3-135 months), 68 (84%) patients are alive. Severe acute (III-IV) or chronic graft versus host disease occurred in 11% and 10%, respectively. Causes of death were infections (n = 5), graft versus host disease (5), multiorgan failure (2), and preexistent lymphoma (1). Survival after matched related (n = 40) or unrelated (35) HSCT was 89% and 81%, respectively. Reduced-toxicity conditioning based on either treosulfan or reduced-dose busulfan resulted in superior survival compared with fully myeloablative busulfan-based regimens (97% vs 78%; P = .049). Ninety-six percent of patients younger than 8 years at HSCT survived, compared with 78% of those 8 years and older (P = .06). Of the 73 patients with chimerism data available, 65 (89%) had more than 90% donor T-cell chimerism at last follow-up. Not all disease manifestations responded equally well to HSCT: eczema, infections, and mollusca resolved quicker than food allergies or failure to thrive., Conclusions: HSCT is curative in most DOCK8-deficient patients, confirming this approach as the treatment of choice. HSCT using a reduced-toxicity regimen may offer the best chance for survival., (Copyright © 2018. Published by Elsevier Inc.)

Monogenic diabetes represents a heterogeneous group of disorders resulting from a single gene defect leading to disruption of insulin secretion or a reduction in the number of beta cells. Despite the classification of monogenic diabetes into neonatal diabetes or maturity onset diabetes of the young (MODY) according to age of onset, not every case can be classified into those 2 groups. We evaluated patients with monogenic diabetes diagnosed during the last 10 year period. Type 1 DM, MODY, and patients with negative autoantibodies and no mutation in a known gene were excluded from the study. Thirteen patients were diagnosed with monogenic diabetes in Department of Pediatric Endocrinology, Ankara University School of Medicine, Ankara, Turkey. Five of them were diagnosed after 6 months of age. Five had a KATP channel defect. Mutations in genes resulting in destruction of beta cells were detected in 7 patients, with 4 cases having a WFS, 2 an LRBA, and one a IL2RA mutation. Additional systemic findings were seen in 6/13 patients, with 5/6 having severe immune system dysfunction. Treatment with sulphonylurea was successful in two patients.. The other patients were given insulin in differing doses. Four patients died during follow-up, three of which had immune system dysfunction. Monogenic diabetes can be diagnosed after 6 months of age, even with positive autoantibodies. Immune dysfunction was a common feature in our cohort and should be investigated in all patients with early-onset monogenic diabetes. Mortality of patients with monogenic diabetes and additional autoimmunity was high in our cohort and is likely to reflect the multisystem nature of these diseases., Competing Interests: No conflict of interest has been declared by the authors., (© Georg Thieme Verlag KG Stuttgart · New York.)

Telomeres are repetitive hexameric sequences located at the end of linear chromosomes. They adopt a lariat-like structure, the T-loop, to prevent them from being recognized as DNA breaks by the DNA repair machinery. RTEL1 is a DNA helicase required for proper telomere replication and stability. In particular, it has been postulated that RTEL1 is involved in the opening of the T-loop during telomere replication to avoid sudden telomere deletion and telomere circle (T-circle) formation. In humans, biallelic RTEL1 mutations cause Hoyeraal-Hreidarsson syndrome (HH), a rare and severe telomere biology disorder characterized by intrauterine growth retardation, bone marrow failure, microcephaly and/or cerebellar hypoplasia, and immunodeficiency. To date, 18 different RTEL1 mutations have been described in 19 cases of HH with short telomeres. The impaired T-loop resolution has been proposed to be a major cause of telomere shortening in RTEL1 deficiency. However, the biological and clinical consequences of this disorder remain incompletely documented. Here, we describe 4 new patients harboring biallelic RTEL1 mutations, including 2 novel missense mutations located in the C-terminal end of RTEL1 (p.Cys1268Arg and p.Val1294Phe). Clinical characteristics from these 4 patients were collected as those from 4 other RTEL1-deficient patients previously reported. In addition, we assessed whether T-circles, the product of improper T-loop resolution, were detected in our RTEL1-deficient patients. Overall, our study broadens and refines the clinical and biological spectrum of human RTEL1 deficiency., Competing Interests: Conflict-of-interest disclosure: The authors declare no competing financial interests.

Objective: It is suggested that vitamin D is one of the factors that can regulate the function of Treg cells. In this study, the relationships between Treg cells and vitamin D levels was investigated in pediatric chronic autoimmune thyroiditis (CAT) patients., Methods: Thirty-two children with CAT and 24 healthy subjects were studied. FOXP3 expressing CD4+CD25+high Foxp3+T cells were identified as Treg cells. At diagnosis, 25-hydroxycholecalciferol (25OHD3) levels were determined in all patients. FOXP3 expression was measured before and after vitamin D replacement therapy in patients having low levels of 25OHD3., Results: In the CAT patients, Treg cell levels did not differ from the control group, while the frequency of vitamin D deficiency was higher and FOXP3 molecule expression was lower. FOXP3 molecule expression significantly increased in CAT patients having vitamin D deficiency who were given vitamin D replacement., Conclusion: FOXP3 expression is decreased in pediatric CAT patients. This reduction seems to be associated with vitamin D levels. Vitamin D can play a role in enhancing natural Treg cell functions.

Interleukin (IL)-13 has been reported to have a role in the pathogenesis of lymphoma through recent molecular studies predominantly in adult patients. As malignant lymphomas in children differ from adult counterparts in terms of histology and response to treatment, we aimed to determine the serum IL-13 levels of patients with lymphoma; its relation with clinical-laboratory parameters and to look for any correlation of serum IL-13 levels with different prognostic factors in children. Twenty-eight patients with malignant lymphoma and 20 age-matched healthy controls were included in the study. The median serum IL-13 level at diagnosis (range 0.59-68 pg/ml, median 3.40 pg/ml) was higher than that in remission (range 0.14-12.2 pg/ml, median 1.60 pg/ml) in the HL group (p < 0.05). Remarkably, median serum IL-13 level of patients with nodular sclerosis at diagnosis was higher than those with mixed-cellularity (p < 0.05) and declined to normal limits during remission (p < 0.05). In Burkitt's lymphoma (BL) subgroup, the median (range 2.94-154 pg/ml, median 4.5 pg/ml) was high and declined to normal levels during remission (range 0.55-11.30 pg/ml, median 1.57 pg/ml) and the difference was significant (p < 0.05). In terms of prognostic factors, serum IL-13 levels were found to be associated with white blood cells counts only in HL group. Although the number of patients is limited in our study, we found that the serum IL-13 levels exhibit variances in different histopathologic groups. IL-13 might have a role in histopathogenesis of lymphoma, but seems to have no prognostic significance. Nevertheless, more molecular studies are needed to evaluate the pathogenesis of HL.

Background Combined immunodeficiencies are marked by inborn errors of T-cell immunity in which the T cells that are present are quantitatively or functionally deficient. Impaired humoral immunity is also common. Patients have severe infections, autoimmunity, or both. The specific molecular, cellular, and clinical features of many types of combined immunodeficiencies remain unknown. Methods We performed genetic and cellular immunologic studies involving five unrelated children with early-onset invasive bacterial and viral infections, lymphopenia, and defective T-cell, B-cell, and natural killer (NK)-cell responses. Two patients died early in childhood; after allogeneic hematopoietic stem-cell transplantation, the other three had normalization of T-cell function and clinical improvement. Results We identified biallelic mutations in the dedicator of cytokinesis 2 gene (DOCK2) in these five patients. RAC1 activation was impaired in the T cells. Chemokine-induced migration and actin polymerization were defective in the T cells, B cells, and NK cells. NK-cell degranulation was also affected. Interferon-α and interferon-λ production by peripheral-blood mononuclear cells was diminished after viral infection. Moreover, in DOCK2-deficient fibroblasts, viral replication was increased and virus-induced cell death was enhanced; these conditions were normalized by treatment with interferon alfa-2b or after expression of wild-type DOCK2. Conclusions Autosomal recessive DOCK2 deficiency is a new mendelian disorder with pleiotropic defects of hematopoietic and nonhematopoietic immunity. Children with clinical features of combined immunodeficiencies, especially with early-onset, invasive infections, may have this condition. (Supported by the National Institutes of Health and others.).

Chronic granulomatous disease (CGD) is an autosomal recessive or X-linked disorder caused by NADPH oxidase deficiency leading to an impaired ability of reactive superoxide anion and metabolite formation and recurring severe bacterial and fungal infections, with a high mortality rate. Diarrhea, colitis, ileus, perirectal abscess formation and anal fissures are reported gastrointestinal findings in these patients. We report a case of intractable colitis associated with CGD in a young girl.

Primary immunodeficiency disorders enable identification of genes with crucial roles in the human immune system. Here we study patients suffering from recurrent bacterial, viral and Cryptosporidium infections, and identify a biallelic mutation in the MAP3K14 gene encoding NIK (NF-κB-inducing kinase). Loss of kinase activity of mutant NIK, predicted by in silico analysis and confirmed by functional assays, leads to defective activation of both canonical and non-canonical NF-κB signalling. Patients with mutated NIK exhibit B-cell lymphopenia, decreased frequencies of class-switched memory B cells and hypogammaglobulinemia due to impaired B-cell survival, and impaired ICOSL expression. Although overall T-cell numbers are normal, both follicular helper and memory T cells are perturbed. Natural killer (NK) cells are decreased and exhibit defective activation, leading to impaired formation of NK-cell immunological synapses. Collectively, our data illustrate the non-redundant role for NIK in human immune responses, demonstrating that loss-of-function mutations in NIK can cause multiple aberrations of lymphoid immunity.

Purposes: The aims of this study were to review the frequency, characteristics, and the clinical course of primary immunodeficiency (PID) patients admitted to pediatric intensive care unit (PICU) and attempt to identify factors related with mortality that might predict a poor outcome., Methods: We performed a retrospective review of children with PID aged 1 month to 18 years and admitted to PICU from January 2002 to January 2012 in our tertiary teaching children's hospital., Results: There were a total of 51 patients accounting for 71 admissions to the PICU. The most common diagnosis was severe combined immunodeficiency. Respiratory problems were the leading cause for admission. A total of 20 patients received hematopoietic stem cell transplantation. Immune reconstitution was achieved in 9 (45 %) patients and eight of them did survive. In all 56 % of all admission episodes resulted in survival. Risk factors for mortality included requirement of mechanical ventilation (P < .001), number of organ system failure (P = .013), need for renal replacement therapy (P < .001), use of inotropes (P < .001), higher Pediatric Logistic Organ Dysfunction (PELOD) score (P = .005), and length of PICU stay (P < .001)., Conclusions: This is the first study regarding the outcome and mortality-related risk factors for PID patients requiring PICU admission. We suggest that PICU management is as important as early diagnosis and treatment for these patients. Prediction of those at risk for poorer outcome might be beneficial for accurate intensive care management and survival.

Background: The pathogenesis of some primary humoral immunodeficiencies, such as transient hypogammaglobulinemia of infancy (THI) and immunoglobulin (Ig) A deficiency, remains unknown and can render diagnosis problematic., Objective: In the present study, we used flow cytometry to analyze peripheral blood B-cell subsets in patients with THI and unclassified hypogammaglobulinemia (UCH), partial IgA deficiency, and selective IgM deficiency., Methods: The study population comprised 41 patients with hypogammaglobulinemia (THI, 18; UCH, 23), 16 patients with partial IgA deficiency, and 16 patients with selective IgM deficiency who were admitted to Ankara University Department of Pediatric Immunology-Allergy between January 2010 and April 2011, as well as 29 healthy controls. B-cell subsets were examined according to the EUROclass classification., Results: Age at diagnosis in the hypogammaglobulinemia group ranged between-14 months and 13 years (median, 26 months). Naive B-cell percentages were significantly higher and activated B-cell values lower in the THI patients than in the UCH patients and age-matched healthy controls. Nonswitched (IgM+CD27+IgD+) memory B-cell values were found to be significantly lower in patients with selective IgM deficiency than in healthy controls. No significant differences in B-cell subsets were found in patients with partial IgA deficiency., Conclusions: Previous reports show that reduced class-switched memory B cell values are associated with CVID, THI, and selective IgA deficiency. Our findings did not support these reports. Furthermore, we observed that naive B cell values were higher in patients with THI. A maturation defect could play a role in the pathogenesis of THI.

Unlabelled: Pressure-induced urticaria is a non-immunoglobulin E-mediated type of urticaria. Some patients only have angioedema, and the term pressure-induced angioedema (PIA) is more appropriate for them. PIA has not previously been reported in association with endotracheal tube. Here we describe two patients who developed PIA after endotracheal intubation. There were no histories of angioedema, drug and food allergy in both patients. Tests for specific aero-allergens and latex were negative. Serum total immunoglobulin E and C4 levels were in normal ranges. Antihistamines and intravenous steroid therapy were ineffective. Angioedema regressed with intravenous epinephrine infusion and did not relapse after extubation., Conclusion: We suggest that endotracheal tubes can cause PIA. Epinephrine therapy should be used early at treatment, especially in the patients who are at great risk for life-threatening airway problems.

Natural regulatory T (nTreg) cells are described by expression of a specific transcription factor, FOXP3, on CD4+CD25+ cells. They play very important roles in the suppression of allergic reactions and disorders. The aim of this study was to obtain peripheral blood Treg levels among atopic asthmatic patients before and during inhaled steroid treatment and to observe the effect of these cells on the pathogenesis and treatment of asthma. CD4+CD25+FOXP3+ T cells obtained from 20 healthy donors and from 16 atopic asthmatic patients before and after inhaled glucocorticoid treatment were examined by flow cytometer. The levels of CD4+CD25+ FOXP3+ Treg cells were higher in asthmatic children who had been receiving inhaled glucocorticoids, when compared to the control group and to the patients' levels before treatment (p<0.05). The present study suggests that at least one of the anti-inflammatory effects of inhaled glucocorticoids in asthma depends upon induction of Treg cells.

The aims of the study were to examine the distribution of Candida spp. isolated from sterile body sites, the antifungal susceptibility of the isolates to amphotericin B, fluconazole, voriconazole, and caspofungin, and factors affecting mortality with invasive Candida infections in children. Thirty-five children with invasive candidiasis between January 2004 and January 2008 were evaluated retrospectively. The antifungal susceptibility of isolated Candida species was studied by Etest. Of the invasive Candida infections, 65.7% were due to C. albicans. The second most common isolated species was C. parapsilosis (11.4%). The rates of resistance to fluconazole, amphotericin B and voriconazole were 8.5%, 2.8% and 5.7%, respectively. Caspofungin was the most effective antifungal agent. 22.8% of the patients died in the first 30 days. In univariate analyses, increased mortality was associated with stay in the intensive care unit, the presence of central venous catheter (CVC), failure to remove CVC, and mechanical ventilation.

DiGeorge syndrome (DGS) has classically been characterized by the triad of clinical features including congenital cardiac defects, immune deficiencies secondary to aplasia or hypoplasia of the thymus, and hypocalcaemia due to small or absent parathyroid glands. The phenotypic features of these patients are much more variable and extensive than previously recognized. The acknowledgement of similarities and phenotypic overlap of DGS with other disorders associated with genetic defects in 22q11 has led to an expanded description of the phenotypic features of DGS including palatal/speech abnormalities, as well as cognitive, neurological and psychiatric disorders. Here, we report the cases of two DGS patients with dysmorphic facial features who were initially admitted to the Psychiatry Department for attention disorder and learning difficulties., (©Journal of Clinical Research in Pediatric Endocrinology, Published by Galenos Publishing.)

Catheter related infections are reported as one of the most common source of nosocomial infections. Rhizobium radibacter infections are generally manifested by fever and leukocytosis. Here, a 14 months-old girl diagnosed as T (-) B (-) NK (+) severe combined immunodeficiency (SCID) is presented. She had received repeated (x3) unconditioned haploidentical hematopoetic stem cell transplantations. During the follow-up, she has been arised an asymptomatic infection with R. Radiobacter, which was isolated from central venous catheter and peripheral blood while she was clinically stable, free of symptoms, fever or leukocytosis. She was treated successfully with cefepime and amikacin and did not require catheter removal. So, it is once more clear that the blood cultures should be obtained on regular basis from all patients with an intravascular device, even they were asymptomatic.

HC is a common complication following HSCT. Risk factors include viral infections, cyclophosphamide and busulfan usage, pelvic irradiation, older age at transplantation, allogeneic HSCT and GvHD. The severity of HC ranges from mild hematuria to life-threatening bleeding. Here, we present a seven-and-a-half-yr-old boy with Wiskott-Aldrich syndrome who experienced a late onset Grade III hemorrhagic cystitis following HSCT from his fully matched sibling. A Grade I GvHD localized to skin developed on day +11 and prednisolone therapy was given between the 11th and 22nd d. Myeloid and platelet engraftments were achieved +13 and +16 d, respectively. A gross hematuria began on the 21st post-transplant day. The urine cultures for bacterial or fungal organisms were negative. Urine analysis by PCR revealed a CMV viruria. Following systemic ganciclovir treatment, urinary CMV became negative but hemorrhagic cystitis did not improve. Due to the probability of existing BK virus or adenovirus, two doses of cidofovir were administered intravesically. As he continued to have painful hematuria with large clot formations, two doses of intravesical hyaluronic acid were applied. Macroscopic hematuria resolved within four d after the second dose. Complete remission was achieved on day +77. Finally, intravesical administration of hyaluronic acid seems to be effective and safe and can be a promising treatment in patients suffering from severe and late onset HC.

Primary immunodeficiencies (PIDs) are a relatively common occurrence in countries where consanguineous marriages are widespread. A principal factor leading to misdiagnosis and ensuing complications can be the lack of knowledge and proper evaluation. The aim of this study was to assess PID awareness and the identification of diagnostic criteria leading to correct diagnosis. Seven hundred eighty-six questionnaires with 71 items were distributed to physicians attending the 41st National Congress of Pediatrics (2005) and to pediatric residents of two university hospitals from different cities in Turkey. The 217 completed questionnaires revealed that family history (91.2%), consanguineous marriages (87.1%), infant deaths (70.0%), persistent thrush (90.3%), hospitalization for recurrent cellulitis (70.5%), chronic diarrhea due to giardiasis (62.2%), recurrent oral aphthous lesions (58.5%), telangiectasia (82.0%), failure to thrive (78.8%), absence of tonsil tissue (74.7%), oculocutaneous albinism (73.7%), and resistant sinusitis (71.0%) were cited among important indicators of PID. However, neonatal tetany (77.9%), liver abscess (61.3%) and poliomyelitis following oral polio vaccination (51.2%) were not considered as related to PID. Although white blood cell (WBC) and differential were chosen as the preferred initial tests, leukocytosis and lymphopenia were also not judged as related to PID. More comprehensive pre/postgraduate education in PID appears to be necessary for physicians in Turkey.

Central venous catheter (CVC) fracture with embolization is a serious and rare complication, and few cases have been reported in children. Catheter fragments may cause cardiac perforation, arrythmias, pulmonary embolism, and sepsis. We report the successful retrieval of intracardiac CVC fragments by percutaneous transcatheter technique in two infants, aged 8 and 15 months. Double-lumen 7 French Hickman CVCs were accidentally fractured during their removal. Chest radiographs of the two patients revealed migrated intracardiac catheter fragments extending from the superior vena cava (SVC) to the right atrium and from the SVC to the right ventricle, respectively. The procedure was performed under ketamine anesthesia and fluoroscopic guidance using a percutaneous femoral vein approach. Nitinol Amplatz Goose Neck snares (10 mm in diameter) were used to successfully retrieve the catheter fragments without any complication. Percutaneous transcatheter retrieval of catheter fragments using Goose Neck snare is a safe and successful technique and can be chosen before resorting to surgery, which has potential risks related to general anesthesia, thoracotomy and cardiopulmonary bypass.

TGF-Beta1 is a pro and antiinflammatory cytokine and plays an important role in airway remodelling in asthma. TNF-alpha is a proinflammatory cytokine that involved in the pathogenesis of asthma. Cytokine production is under genetic control, and certain single nucleotide polymorphisms (SNPs), which lead to allelic variants of cytokine genes are associated with higher or lower cytokine production in vitro. In some studies TGF-Beta1-915G/C and TNF-alpha-308G/A polymorphisms are found to be more prevalent and associated with asthma. The aim of this study is to investigate the frequency of TGF-Beta1-915G/C and TNF-alpha-308G/A polymorphisms and to determine whether or not these polymorphisms are associated with the development of asthma in children. 46 asthmatic children and 67 healthy controls were investigated by LightCycler PCR analysis for TGF-Beta1-915G/C and TNF-alpha-308G/A polymorphisms. The frequency of TGF-Beta1-915G/C and TNF-alpha-308G/A polymorphisms in asthmatic children were 15.2% and 23.9% respectively while the corresponding figures were 8.9% and 23.8% in the control group (p> 0.05). The risk of asthma development was not associated for TGF-Beta1 915G/C (OR: 0.54, 95% CI: 0.17-1.75) and TNF-alpha-308G/A (OR: 0.99, 95% CI: 0.41-2.40) polymorphisms. These results indicated that, the frequency of TGF-Beta1 915G/C and TNF-alpha-308G/A polymorphisms did not show any difference in asthmatic children compared to healthy controls and these polymorphisms do not seem to influence suspectibilty to asthma.

It is a common and well-known fact that infants and preschool children undergo frequent episodes of upper respiratory tract infections. The majority of these children do not have a recognized immunodeficiency. The aim of the present study was to evaluate the effects of frequent upper respiratory tract infections on cellular immunity, using peripheral blood lymphocyte subsets and activation markers as defining parameters. The study group consisted of 16 children (aged 2-6 years) with frequent upper respiratory tract infections; 30 age-matched healthy children served as controls. Peripheral blood T, B, NK cells; T lymphocyte subsets; naive and memory cells; and activation markers were analyzed by using monoclonal antibodies and flow cytometry. White blood cell count (WBC) was found to be markedly increased in the study group compared to controls (p < 0.05). The absolute number of lymphocytes was also higher than that of the healthy children. The relative size of the CD3+CD8+ T lymphocytes and the relative and absolute numbers of CD3-CD16+56+ NK cells were found to be higher in patients than the controls. All the remaining percentages and numbers of the T cell subgroups including naive and memory cells and B lymphocytes did not show any difference, while CD3+CD25+ cell numbers were markedly increased (p < 0.05). In conclusion, the examination of peripheral blood lymphocyte subsets in children with frequent upper respiratory tract infections is important in evaluating cellular immune alterations due to antigenic stimulation; however, it is neither essential nor cost-effective in the management of the disease. This study has shown that both the percentage and absolute numbers of peripheral blood lymphocyte subsets maintain their normal status in children with frequent upper respiratory tract infections.

Autoimmune lymphoproliferative syndrome (ALPS) is a rare childhood disorder characterized by chronic non-malignant lymphoproliferation and autoimmunity. Patients with ALPS frequently exhibit episodic and intermittent, severe autoimmune- induced hemolytic anemia, thrombocytopenia or combined cytopenias. The co-occurrence of immune-mediated cytopenias, autoimmune thrombocytopenia and autoimmune hemolytic anemia is also known as Evans syndrome. This report describes a child who presented with Evans syndrome symptoms and who, after the detection of increased percentage of double negative T cell population in the peripheral blood, was diagnosed as ALPS. He received several courses of treatment including glucocorticoids, cyclosporine A (Cs A), and intravenous immunoglobulin (IVIG) without any clinical benefit and was treated with the antimalarial drug Fansidar®. With administration of Fansidar® (half tablet per week; containing 250 mg of pyrimethamine and 12.5 mg of sulfadoxine) combined with immunosuppressive drugs, clinical status and laboratory findings temporarily improved. After two months, the patient underwent laparoscopic splenectomy because of worsening of thrombocytopenia refractory to the treatment. There was a transient beneficial effect from splenectomy. We were unable to stop immunosuppressive therapy and Fansidar®; however, this combined therapy was successful in decreasing the number of hospitalizations and controlled his clinical symptoms more effectively for six months. Unfortunately, he was admitted to a regional hospital with high fever and died at the age of three.

We describe two siblings (a male patient and his older sister) with a novel mutation in the peptide transporter associated to antigen processing (TAP). The index case presented with not only granulomatous skin lesions and recurrent sino-pulmonary infections, often associated with this deficiency, but also a severe pulmonary toxoplasmosis. His toxoplasmosis and skin lesions were successfully treated.

Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disease characterized by thrombocytopenia, eczema, impaired cellular and humoral immunity, and increased susceptibility to malignancy and autoimmunity. The only curative treatment for WAS is hematopoietic stem cell transplantation, especially in the presence of a matched sibling donor or matched unrelated donor. Here, we report the case of a 2.5-yr-old boy with WAS that resulted in mixed chimerism after having received bone marrow from his phenotypically identical grandfather. Although the patient has persistent thrombocytopenia (platelet counts 50-80 x 10(9)/L), he is currently alive and doing well at 36 months post-transplant and is free of any bleeding episodes.

Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by thrombocytopenia, eczema and immunodeficiency. Clinical features of the disease are highly varied; therefore, the diagnosis is sometimes difficult, especially in solitary cases or cases with milder forms of the disease. However, the identification of the WASP gene has made possible a definite WAS diagnosis for these cases. In this report, we present a 26-month-old boy who had received several ineffective treatments for chronic immune thrombocytopenic purpura. He was then suspected to have WAS because of the early onset of thrombocytopenia and small platelets. The diagnosis became definite with the detection of a de novo mutation at exon 4 of the WASP gene, Arg138Pro, through mutation analysis.