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The group of patients with DNA-repair-defects increases susceptibility to infections due to impaired repertoire diversity. In this context, we aimed to investigate the TCRvβ-repertoire by flow cytometric analysis and its correlation with clinical entities in a group of IEI patients with DNA repair defects. Peripheral lymphocyte subset and TCRvβ-repertoire analyses were performed by flow cytometric analysis. The aim was to explore the changing TCR-Vβ-repertoire that can predict some clinical entities by investigating the repertoire using flow-cytometric-analysis-based TCR-Vβ and its interaction with clinical entities in a group of IEI patients with DNA repair defects. TCR-repertoire of the patients with DNA-repair-defects and healthy controls was analysed with flow-cytometer. The potential of flow-cytometric analysis of the TCR repertoire as a practical and easily accessible clinical prediction method was investigated. Thirty-nine-IEI patients with DNA-repair-defects and 15 age-matched healthy-controls were included in this study. Peripheral lymphocyte subset and TCR-Vβ repertoire analyses were performed by flow cytometry. Compared to the control group, 9 out of 24 clones (37.5%) exhibited a statistically significant reduction, while only 3 clones showed a statistically significant increase (p < 0.05). Preferential use of vβ-genes was associated with some clinical entities. Lower TCR-vβ-9 and TCR-vβ23, higher TCR-vβ7.2 were found in the patients with pneumonia (n = 13) (p = 0.018, p = 0.044 p = 0.032). AT patients with pneumonia had lower TCR-vβ-9 clone than patients without pneumonia (p = 0.008). Skewed proliferation of most TCR-vβ clones was seen DNA-repair-defects, especially AT. In addition, this study showed that preferential use of TCR-vβ genes could be predictive for some clinical entities., (© 2025 The Author(s). Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology.)

Background: Major histocompatibility complex class II deficiency, a combined immunodeficiency, results from loss of HLA class II expression on antigen-presenting cells. Currently, hematopoietic stem cell transplantation stands as the sole curative approach, although factors influencing patient outcomes remain insufficiently explored., Objectives: To elucidate the clinical, immunologic, and genetic profiles associated with MHC-II deficiency and identify prognostic indicators that affect survival rates., Methods: In this multicenter retrospective analysis, we gathered data from 35 patients with a diagnosis of MHC-II deficiency across 12 centers in Turkey. We recorded infection histories, gene mutations, immune cell subsets, and surface MHC-II expression on blood cells. We conducted survival analyses to evaluate the impact of various factors on patient outcomes., Results: Predominant symptoms observed were pneumonia (n = 29; 82.9%), persistent diarrhea (n = 26; 74.3%), and severe infections (n = 26; 74.3%). The RFXANK gene mutation (n = 9) was the most frequent, followed by mutations in RFX5 (n = 8), CIITA (n = 4), and RFXAP (n = 2) genes. Patients with RFXANK mutations presented with later onset and diagnosis compared with those with RFX5 mutations (P =.0008 and .0006, respectively), alongside a more significant diagnostic delay (P = .020). A notable founder effect was observed in five patients with a specific RFX5 mutation (c.616G>C). The overall survival rate for patients was 28.6% (n = 10), showing a significantly higher proportion in individuals with hematopoietic stem cell transplantation (n = 8; 80%). Early death and higher CD8 + T-cell counts were observed in patients with the RFX5 mutations compared with RFXANK-mutant patients (P = .006 and .009, respectively)., Conclusions: This study delineates the genetic and clinical panorama of MHC-II deficiency, emphasizing the prevalence of specific gene mutations such as RFXANK and RFX5. These insights facilitate early diagnosis and prognosis refinement, significantly contributing to the management of MHC-II deficiency., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Molecular diagnosis of inborn errors of immunity (IEI) plays a critical role in determining patients' long-term prognosis, treatment options, and genetic counseling. Over the past decade, the broader utilization of next-generation sequencing (NGS) techniques in both research and clinical settings has facilitated the evaluation of a significant proportion of patients for gene variants associated with IEI. In addition to its role in diagnosing known gene defects, the application of high-throughput techniques such as targeted, exome, and genome sequencing has led to the identification of novel disease-causing genes. However, the results obtained from these different methods can vary depending on disease phenotypes or patient characteristics. In this study, we conducted whole-exome sequencing (WES) in a sizable cohort of IEI patients, consisting of 303 individuals from 21 different clinical immunology centers in Türkiye. Our analysis resulted in likely genetic diagnoses for 41.1% of the patients (122 out of 297), revealing 52 novel variants and uncovering potential new IEI genes in six patients. The significance of understanding outcomes across various IEI cohorts cannot be overstated, and we believe that our findings will make a valuable contribution to the existing literature and foster collaborative research between clinicians and basic science researchers., (© 2024. The Author(s).)

Background: Trichohepatoenteric syndrome (THES) is characterized by neonatal-onset intractable diarrhea. It often requires long-term total parenteral nutrition (TPN). In addition, other characteristic findings of the syndrome include growth retardation, facial dysmorphism, hair abnormalities, various immunological problems and other rare system findings. Two genes and their associated pathogenic variants have been associated with this syndrome: SKIC3 and SKIC2., Methods and Results: In this case series, the clinical findings and molecular analysis results of a total of 8 patients from 5 different families who presented with persistent diarrhea and were diagnosed with THES were shared. Pathogenic variants were detected in the SKIC3 gene in 6 of our patients and in the SKIC2 gene in 2 patients. It was planned to compare the clinical findings of our patients with other patients, together with literature data, and to present yet-undefined phenotypic features that may be related to THES. In our case series, in addition to our patients with a novel variant, patient number 2 had a dual phenotype (THES and Spondyloepimetaphyseal dysplasia, sponastrime type) that has not been reported yet. Delay in gross motor skills, mild cognitive impairment, radioulnar synostosis, osteoporosis, nephropathy and cystic lesions (renal and liver) were observed as unreported phenotypic findings., Conclusions: We are expanding the clinical and molecular repertoire of the syndrome regarding patients diagnosed with THES. We recommend that the NGS (next-generation sequencing) multigene panel should be used as a diagnostic tool in cases with persistent diarrhea., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Primary immune deficiencies (PIDs) are rare genetic disorders characterized by impaired immune function, leading to frequent infections and immune dysregulation. Studies have shown that individuals with PID are at an increased risk of developing malignancies and lymphoproliferative disorders compared with the general population. In this single-center study, we aimed to analyze the occurrence of malignancies and lymphoproliferations in children diagnosed with PID. We retrospectively analyzed the medical records of 550 pediatric patients diagnosed with PIDs at our center. Among them, 17 (3,0%) patients were identified with malignancy and/or benign lymphoproliferation. Eight of the 17 patients (47.0%) had immune dysregulatory diseases, whereas ataxia-telangiectasia was the second most common PID associated with malignancy and/or benign lymphoproliferation (n = 5, 29.4%). Lymphoma was the predominant malignancy (n = 11, 64.7%), and Epstein-Barr virus was identified as the most common viral agent associated with malignancy and/or benign lymphoproliferation in patients with PID (n = 8, 47.0%). Our study highlights the association between PID and malignancies/lymphoproliferations, with immune dysregulation syndromes being the most common subclass associated with malignancies/lymphoproliferations. Early diagnosis, multidisciplinary management, and regular surveillance are crucial in improving patient outcomes and saving lives., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive combined immunodeficiency. The phenotype is profound T cell deficiency with variable B and NK cell functions and results in recurrent and persistent infections that typically begin in the first year of life. Neurologic findings occur in approximately two-thirds of patients. The mechanism of neurologic abnormalities is unclear. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for PNP deficiency., Methods: We report here six patients from five unrelated families with PNP deficiency treated in two centers in Turkey. We evaluated the neurological status of patients and compared to post-transplantation period if available. Then, we performed PubMed, Google Scholar, and Researchgate searches using the terms "PNP" and "hematopoietic stem cell transplantation" to find all reported cases of PNP transplantation and compared to our cohort., Results: Six patients were treated in two centers in Turkey. One patient died from post-transplant complications. The other four patients underwent successful HSCT with good immune reconstitution after transplantation (follow-up 21-48 months) and good neurological outcomes. The other patient with a new mutation is still waiting for a matching HLA donor., Discussion: In PNP deficiency, clinical manifestations are variable, and this disease should be considered in the presence of many different clinical findings. Despite the comorbidities that occurred before transplantation, HSCT currently appears to be the only treatment option for this disease. HSCT not only cures immunologic disorders, but probably also improves or at least stabilizes the neurologic status of patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Food allergies are the most common cause of anaphylaxis in children, and their incidence is increasing globally. The aim of this study was to determine the risk factors leading to food allergies in childhood., Methods: Children with food allergies and non-atopic healthy children were compared using a questionnaire that included prenatal, neonatal, and postnatal risk factors., Results: A total of 314 subjects, 155 patients and 159 healthy children for the control group, were enrolled in the study. The median age of patients with a food allergy at diagnosis was 6 months (1-156 months), and 71 patients (45.8%) were males. The median age of the control group was 12 months (1-61 months), and 67.0% were males. Older maternal age (P = 0.023), birth by caesarean section (P = 0.001), birth in the summer or autumn (P = 0.011), crowded housing (P = 0.001), damp houses (P = 0.001), being fed with breast milk and complementary food (P = 0.001), use of synthetic bedding (P = 0.024), and being the oldest child in the family (P = 0.001) were the considered risk factors for an immunoglobulin-E (IgE)-mediated food allergy. A low frequency of yoghurt consumption by mother (P = 0.001) and use of wool bedding (P = 0.018) were identified as risk factors for non-IgE-mediated food allergies. Low socioeconomic status (P = 0.001) played a protective role against both IgE- and non-IgE-mediated food allergies whereas breastfeeding played a protective role against IgE-mediated food allergies (P = 0.030)., Conclusion: The most important aspect of this study was that it separately identified prenatal, neonatal, and postnatal risk factors for IgE- and non-IgE-mediated food allergies., Competing Interests: The authors declare no potential conflict of interest with respect to research, authorship, and/or publication of this study.

Background: Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency and cytotoxic T-lymphocyte protein-4 (CTLA-4) insufficiency are recently described disorders that present with susceptibility to infections, autoimmunity, and lymphoproliferation. Clinical and immunological comparisons of the diseases with long-term follow-up have not been previously reported. We sought to compare the clinical and laboratory manifestations of both diseases and investigate the role of flow cytometry in predicting the genetic defect in patients with LRBA deficiency and CTLA-4 insufficiency., Methods: Patients were evaluated clinically with laboratory assessments for lymphocyte subsets, T follicular helper cells (T FH ), LRBA expression, and expression of CD25, FOXP3, and CTLA4 in regulatory T cells (Tregs) at baseline and 16 h post-stimulation., Results: LRBA-deficient patients (n = 29) showed significantly early age of symptom onset, higher rates of pneumonia, autoimmunity, chronic diarrhea, and failure to thrive compared to CTLA-4 insufficiency (n = 12). In total, 29 patients received abatacept with favorable responses and the overall survival probability was not different between transplanted versus non-transplanted patients in LRBA deficiency. Meanwhile, higher probability of survival was observed in CTLA-4-insufficient patients (p = 0.04). The T-cell subsets showed more deviation to memory cells in CTLA-4-insufficiency, accompanied by low percentages of Treg and dysregulated cT FH cells response in both diseases. Cumulative numbers of autoimmunities positively correlated with cT FH frequencies. Baseline CTLA-4 expression was significantly diminished in LRBA deficiency and CTLA-4 insufficiency, but significant induction in CTLA-4 was observed after short-term T-cell stimulation in LRBA deficiency and controls, while this elevation was less in CTLA-4 insufficiency, allowing to differentiate this disease from LRBA deficiency with high sensitivity (87.5%) and specificity (90%)., Conclusion: This cohort provided detailed clinical and laboratory comparisons for LRBA deficiency and CTLA-4 insufficiency. The flow cytometric approach is useful in predicting the defective gene; thus, targeted sequencing can be conducted to provide rapid diagnosis and treatment for these diseases impacting the CTLA-4 pathway., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Human Inborn Errors of Immunity (IEIs) are clinically and genetically heterogeneous group of diseases, with relatively mild clinical course or severe types that can be life-threatening. Severe combined immunodeficiency (SCID) is the most severe form of IEIs, which is caused by monogenic defects that impair the proliferation and function of T, B, and NK cells. According to the most recent report by the International Union of Immunological Societies (IUIS), SCID is caused by mutations in IL2RG, JAK3, FOXN1, CORO1A, PTPRC, CD3D, CD3E, CD247, ADA, AK2, NHEJ1, LIG4, PRKDC, DCLRE1C, RAG1 and RAG2 genes. The targeted next-generation sequencing (TNGS) workflow based on Ion AmpliSeq™ Primary Immune Deficiency Research Panel was designed for sequencing 264 IEI-related genes on Ion S5™ Sequencer. Herein, we present 21 disease-causing variants (12 novel) which were identified in 22 patients in eight different SCID genes. Next-generation sequencing allowed a rapid and an accurate diagnosis SCID patients., (© 2022 The Scandinavian Foundation for Immunology.)

Background: Primary immunodeficiency diseases (PID) are characterized by the occurrence of frequent infections and are caused by many genetic defects. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option for the majority of PID. As a Pediatric Hematology-Oncology-Immunology Transplantation Unit, we wanted to present our HSCT experience regarding treatment of primary immunodeficiency diseases., Methods: 58 patients were included in the study between January 2014 and June 2019. We searched 9/10 or 10/10 matched-related donor (MRD) firstly, in the absence of fully matched-related donor. We screened matched unrelated donor (MUD) from donor banks. MRD was used in 24 (41.3%) patients, MUD in 20 (34.4%) patients, and haploidentical donors in 14 (24.1%) patients. Demographic data, HSCT characteristics, and outcome were evaluated. While 16 patients had severe combined immunodeficiency (SCID), the remaining was non-SCID., Results: Of the 58 patients, 38 were male and 20 were female. Median age at transplantation was 12 months (range: 2.5-172 months). Combined immunodeficiencies consisted 67.2% of patients. Mean follow-up time was 27 months (6 months-5 years). Median neutrophil, lymphocyte, and thrombocyte engraftment days were similar in comparison of both donor type and stem cell source. The most common complication was acute GvHD in 15 (25.8%) patients. In total, five patients (31%) belonging to the SCID group and 10 patients (23.8%) belonging to the non-SCID group died. Our total mortality rate was 15 (25.8%) in all patients., Conclusions: We would like to present our HSCT experiences as a pediatric immunology transplantation center. Existing severe infections before transplantation period, BCGitis, and CMV are important issues of transplantation in Turkey. However, the follow-up time is shorter than some studies, our results regarding complications and survival are similar to previous reports., (© 2021 Wiley Periodicals LLC.)

Background: Several factors that increase the risk of severe food-induced anaphylaxis have been identified. Objective: We aimed to determine the demographic, etiologic, and clinical features of food-induced anaphylaxis in early childhood and also any other factors associated with severe anaphylaxis. Methods: We carried out a medical chart review of anaphylaxis cases from 16 pediatric allergy and immunology centers in Turkey. Results: The data of 227 patients with 266 food-induced anaphylaxis episodes were included in the study. The median (interquartile range) age of the first anaphylaxis episode was 9 months (6-18 months); 160 of these patients were boys (70.5%). The anaphylaxis episodes were mild in 75 cases (28.2%), moderate in 154 cases (57.9%), and severe in 37 cases (13.9%). The most frequent food allergens involved were cow's milk (47.4%), nuts (16.7%), and hen's egg (15.8%). Epinephrine was administered in only 98 (36.8%) of these anaphylaxis episodes. A logistic regression analysis revealed two statistically significant factors that were independently associated with severe anaphylaxis: the presence of angioedema and hoarseness during the anaphylactic episode. Urticaria was observed less frequently in patients who developed hypotension. In addition, confusion and syncope were associated with 25.9- and 44.6-fold increases, respectively, in the risk of concomitant hypotension. Conclusion: Cow's milk, nuts, and hen's egg caused the majority of mild and moderate-to-severe anaphylaxis episodes. The presence of angioedema and hoarseness in any patient who presents with a history of food-induced anaphylaxis should alert clinicians that the reaction may be severe. In addition, the presence of confusion, syncope, or stridor probably indicates concomitant hypotension.

Background: Coronavirus disease 2019 (COVID-19) emerged as a pandemic toward the end of 2019, causing large numbers of people to become infected and die., Objective: To determine whether allergic diseases are a risk factor for hospitalization in COVID-19., Methods: We conducted a study including 107 pediatric patients after COVID-19 recovery. The International Study of Asthma and Allergies in Childhood Phase 3 questionnaires were distributed together with a detailed history of environmental factors and an allergic evaluation including skin prick tests, specific immunoglobulin E tests, and spirometry. We investigated the prevalence of allergic diseases and evaluated the factors associated with hospitalization in COVID-19., Results: A total of 61 (57%) patients were hospitalized and 46 (43%) patients were followed closely in the outpatient clinic. The prevalences of allergic rhinitis, asthma, atopic dermatitis, and episodic wheezing were 10.3%, 6,5%, 4.7%, and 3.7%, respectively, within the whole study population. Although having asthma with or without allergic rhinitis, atopic dermatitis, and passive tobacco exposure were not found to be related to hospitalization because of COVID-19, having a pet at home was found to decrease the risk of hospitalization (odds ratio, 0.191; 95% confidence interval, 0.047-0.779; P = .02). Spirometry tests revealed a higher forced expiratory volume in one second to forced vital capacity ratio and a peak expiratory flow reversibility in hospitalized patients than in nonhospitalized ones (P = .02 and P = .003, respectively)., Conclusion: Asthma and allergic diseases do not seem to be risk factors for hospitalization in children because of COVID-19, and having a pet at home can be a protective effect. Pulmonary function testing seems to be important for monitoring lung damage after COVID-19., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: LPS-responsive beige-like anchor (LRBA) deficiency presents with susceptibility to infections, autoimmunity, and lymphoproliferation. The long-term efficacy of cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin (abatacept) as targeted therapy for its immune dysregulatory features remains to be established., Objective: To determine the clinical and immunologic features of LRBA deficiency and long-term efficacy of abatacept treatment in controlling the different disease manifestations., Methods: Twenty-two LRBA-deficient patients were recruited from different immunology centers and followed prospectively. Eighteen patients on abatacept were evaluated every 3 months for long-term clinical and immunologic responses. LRBA expression, lymphocyte subpopulations, and circulating T follicular helper cells were determined by flow cytometry., Results: The mean age of the patients was 13.4 ± 7.9 years, and the follow-up period was 3.4 ± 2.3 years. Recurrent infections (n = 19 [86.4%]), immune dysregulation (n = 18 [81.8%]), and lymphoproliferation (n = 16 [72.7%]) were common clinical features. The long-term benefits of abatacept in 16 patients were demonstrated by complete control of lymphoproliferation and chronic diarrhea followed by immune dysregulation, most notably autoimmune cytopenias. Weekly or every other week administration of abatacept gave better disease control compared with every 4 weeks. There were no serious side effects related to the abatacept therapy. Circulating T follicular helper cell frequencies were found to be a reliable biomarker of disease activity, which decreased on abatacept therapy in most subjects. However, high circulating T follicular helper cell frequencies persisted in 2 patients who had a more severe disease phenotype that was relatively resistant to abatacept therapy., Conclusions: Long-term abatacept therapy is effective in most patients with LRBA deficiency., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose: Adenosine deaminase 2 (ADA2) have been reported to cause vasculitic diseases and immunodeficiency recently. Patients present with stroke episodes and rashes mimicking polyarteritis nodosa (PAN). We report a patient who has been followed up with severe neutropenia and found an unexpectedly revealed novel mutation in CECR1 affecting ADA2., Methods: We reviewed medical records and clinical history of the patient. No mutations in other known neutropenia genes such as ELA, G6PC3, HAX1, AP3B1, LAMTOR2, VPS13B, VPS45, GFI1, JAGN1, or WAS could be detected. Sanger sequencing was used to confirm the genetic variants in the patient and relatives., Results: Genetic analysis by exome sequencing revealed a novel mutation in the gene CECR1 (c.G962A; p.G321E) which segregated perfectly in the relatives., Conclusion: This is the first DADA2 patient presenting with severe neutropenia. We suggest that in patients with unexplained cytopenias combined with immunodeficiency, fevers of unknown origin and high inflammation markers, DADA2 should be considered.

Mutations in T-cell antigen receptor (TCR) subunit genes cause rare immunodeficiency diseases characterized by impaired expression of the TCR at the cell surface and selective T lymphopenia. Here, detailed analyses of spontaneously arising somatic mutations that recover CD247, and thus TCR expression, in a newly identified CD247-deficient patient are described. The recovery of CD247 expression in some patient T cells was associated with both reversion of the inactivating mutation and a variant with a compensating mutation that could reconstitute TCR expression, but not as efficiently as wild-type CD247. Multiple mutations were found in CD247 complementary DNAs (cDNAs) cloned from the patient as well as in cDNA and genomic DNA from other individuals, suggesting that genetic variation in this gene is frequent. Analyses of other genes mutated in primary immunodeficiency diseases (PIDs) where reversions have been described also revealed a higher rate of mutation than that observed for genes mutated in PIDs where revertants have not been identified or control genes. These data support the hypothesis that the occurrence of somatic mutations that may reconstitute genetic defects in PID is related to an increased propensity of those genes to mutate., (© 2017 by The American Society of Hematology.)

Intravenous immunoglobulin (IVIG) is commonly used in primary and secondary immunodeficiency diseases as well as autoimmune conditions as immunomodulatator treatment. Immediate adverse events which are generally mild and occur during infusion are seen in 6 hours. Reported immediate adverse events are in a wide range from 1%-40% in pediatric patients. 115 patients who received IVIG (except newborns) were included into this crosssectional study. IVIG was given to patients for primary immunodeficiencies (n=8), ITP (n=65), Kawasaki disease (n=11), secondary immunosupression (n=28), and passive immunization (n=3). 5%, 10% IVIG preparations and pentaglobin were used. Headache, fever, chills, nausea, rash, arthralgia, myalgia and back pain were accepted as mild immediate events. There were 62 (54%) boys and 53 (46%) girls aged 1 month-18 years. Mean age of the group was 7.4±4.6 years. Immediate adverse events due to IVIG infusions were seen in 29 (25.2%) of all patients. Gender and types of the disease were not different in significance regarding the presence of adverse events. The rate of adverse events did not change with receiving pre-medication. The most common reaction was fever/chills. Immediate reactions were seen in first 6 hours in 7 patients and during infusion in the remaining. They were treated with slowing of the infusion rate and infusion was stopped in 3 patients because of moderate events. Because of the increasingly use of IVIG therapy, it is important to know the side effects. High doses, high infusion rates, accompanying infection may worsen the adverse effects especially in primary immunodeficiency diseases.

Background: Mutations in the HAX-1 gene cause an autosomal recessive form of severe congenital neutropenia (SCN), which particularly manifests with recurrent skin, lung and deep tissue infections from the first few months of life., Objective: We retrospectively evaluated the clinical and laboratory findings of the patients diagnosed with SCN carrying HAX1 gene mutations., Methods: A total of five patients with SCN, carrying a HAX1 gene mutation, were evaluated in terms of clinical and laboratory findings. Mutation analysis of the candidate genes (HAX1, ELANE and CSF3R) was performed., Results: All of the patients lived in Turkey; four of them were of Kurdish origin and one was Turkish. Of the five patients, three were girls and two were boys, and the mean age of the patients was 8.8 years old (range 4-15 years). The mean age of diagnosis was 25.8 months (range 2 months-5 years). The infections diagnosed included recurrent gingivitis, stomatitis, and skin and soft tissue abscesses. Developmental retardation and epilepsy were present in only one patient, whereas speech retardation was present in two. All of our patients had a HAX1 mutation, and are still alive and none of them has shown malignant transformation yet., Conclusion: Complete blood count should be performed and absolute neutrophil count should be evaluated in patients with recurrent severe infections. In the event that neutropenia is detected, they should be investigated in terms of SCN and mutation analysis should be performed.

Background. Tuberculosis (TB) still remains a growing public health problem globally. TB in children is often diagnosed clinically. Methods. We conducted a retrospective chart review of children with TB from November 2004 through December 2010 to determine the appropriateness of using contact history and diagnostic testing. Results. A total of 250 children with TB were identified. One hundred and sixty-two children had only pulmonary disease while 39 had features of both extrapulmonary and pulmonary TB. Mean age was 7.8 years. Thirty-six patients had known contacts. The index case/cases were first-degree relatives in 75%. Sixteen patients who were symptomless were yielded by contact investigation of newly identified TB cases. Tuberculin skin test positivity was 53.3%. Acid-fast bacilli smear positivity was 13.1%, and culture positivity was 18.7%. Twenty-six patients had histopathology of nonrespiratory specimens (lymph nodes and other tissues) showing granulomatous inflammation and caseous necrosis consistent with TB. Conclusions. Presence of contact history directed us to search for TB in children with nonspecific symptoms even if physical examinations were normal. Some children who were close contacts to TB cases were identified to have TB before development of symptoms.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Artemis, DNA ligase IV, DNA protein kinase catalytic subunit, and Cernunnos/XLF genes in nonhomologous end joining pathways of DNA repair mechanisms have been identified as responsible for radiosensitive SCID. Here, we present a 3-year-old girl patient with severe growth retardation, bird-like face, recurrent perianal abscess, pancytopenia, and polydactyly. Firstly, she was thought as Fanconi anemia and spontaneous DNA breaks were seen on chromosomal analysis. After that DEB test was found to be normal and Fanconi anemia was excluded. Because of that she had low IgG and IgA levels, normal IgM level, and absence of B cells in peripheral blood; she was considered as primary immunodeficiency, Nijmegen breakage syndrome. A mutation in NBS1 gene was not found; then Cernunnos/XLF deficiency was investigated due to clinical similarities with previously reported cases. Homozygous mutation in Cernunnos/XLF gene (NHEJ1) was identified. She is now on regular IVIG prophylaxis and has no new infection. Fully matched donor screening is in progress for bone marrow transplantation which is curative treatment of the disease. In conclusion, the patients with microcephaly, bird-like face, and severe growth retardation should be evaluated for hypogammaglobulinemia and primary immunodeficiency diseases.

Objective: To evaluate the direct medical cost of hospital admissions for patients with varicella (i.e., chickenpox) to assess the cost burden of varicella from a health care perspective for ultimate use in health economics studies in Turkey., Methods: Records of children hospitalized with varicella at the Bakirkoy Maternity and Children's Hospital between November of 2006 and June of 2011 were reviewed. Reasons for hospitalization, types of varicella-associated complications, and direct medical cost of hospitalization were noted. Patients with underlying risk factors were excluded. Data obtained from one hospital were used to estimate the national cost of the disease., Results: During the 4.5-year study period, 234 patients were hospitalized with varicella. Of these cases, 48 (20%) children previously ill with underlying cancers or chronic diseases were excluded from the study. Ultimately, 186 previously healthy children (age range: 14 days to 159 months, median age: 14 months) were included. The main reasons for hospitalization were complications related to varicella (79%), the most frequent of which was skin and soft tissue infections, followed by neurological complications and pneumonia. The median cost of hospitalization per patient was US $283, 50% of which was attributed to medication costs. The annual cost for varicella hospitalizations in Turkey was estimated at US $396,200., Conclusions: A significant number of healthy children are hospitalized for varicella and associated complications. Descriptions of these complications and their related costs provide important data for cost-effectiveness studies for decisions about the inclusion of the varicella vaccine in a childhood vaccination program., (Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.)

Background and Objectives: In the last decade, autosomal recessive IL-12Rβ1 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from Morocco, Spain, and Turkey, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12Rβ1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common., Methods and Principal Findings: We searched for IL12RB1 mutations in a series of 50 children from Iran, Morocco, and Turkey. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from Iran and another from Morocco, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12Rβ1 deficiency. Despite the small sample studied, our findings suggest that IL-12Rβ1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease., Significance: This finding may have important medical implications, as recombinant IFN-γ is an effective treatment for mycobacterial infections in IL-12Rβ1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity.