Publications by authors named "Sukru Cekic"

26 Publications

  • Page 1 of 1

Primary antibody deficiencies in Turkey: molecular and clinical aspects.

Immunol Res 2021 Oct 7. Epub 2021 Oct 7.

Istanbul University Graduate School of Health Sciences, Istanbul, Turkey.

Primary antibody deficiencies (PAD) are the most common subtype of primary immunodeficiencies, characterized by increased susceptibility to infections and autoimmunity, allergy, or malignancy predisposition. PAD syndromes comprise of immune system genes highlighted the key role of B cell activation, proliferation, migration, somatic hypermutation, or isotype switching have a wide spectrum from agammaglobulinemia to selective Ig deficiency. In this study, we describe the molecular and the clinical aspects of fifty-two PAD patients. The most common symptoms of our cohort were upper and lower respiratory infections, bronchiectasis, diarrhea, and recurrent fever. Almost all patients (98%) had at least one of the symptoms like autoimmunity, lymphoproliferation, allergy, or gastrointestinal disease. A custom-made next-generation sequencing (NGS) panel, which contains 24 genes, was designed to identify well-known disease-causing variants in our cohort. We identified eight variants (15.4%) among 52 PAD patients. The variants mapped to BTK (n = 4), CD40L (n = 1), ICOS (n = 1), IGHM (n = 1), and TCF3 (n = 1) genes. Three novel variants were described in the BTK (p.G414W), ICOS (p.G60*), and IGHM (p.S19*) genes. We performed Sanger sequencing to validate pathogenic variants and check for allelic segregation in the family. Targeted NGS panel sequencing can be beneficial as a suitable diagnostic modality for diagnosing well-known monogenic PAD diseases (only 2-10% of PADs); however, screening only the coding regions of the genome may not be adequately powered to solve the pathogenesis of PAD in all cases. Deciphering the regulatory regions of the genome and better understanding the epigenetic modifications will elucidate the molecular basis of complex PADs.
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http://dx.doi.org/10.1007/s12026-021-09242-zDOI Listing
October 2021

Food-induced anaphylaxis in early childhood and factors associated with its severity.

Allergy Asthma Proc 2021 Sep;42(5):e135-e144

Pediatric Allergy and Immunology Department, Faculty of Medicine, Sakarya University, Sakarya, Turkey.

Several factors that increase the risk of severe food-induced anaphylaxis have been identified. 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. We carried out a medical chart review of anaphylaxis cases from 16 pediatric allergy and immunology centers in Turkey. 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. 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.
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http://dx.doi.org/10.2500/aap.2021.42.210051DOI Listing
September 2021

Clinical and laboratory findings in patients with leukocyte adhesion deficiency type I: A multicenter study in Turkey.

Clin Exp Immunol 2021 Oct 5;206(1):47-55. Epub 2021 Aug 5.

Division of Pediatric Immunology, Department of Pediatrics, Hacettepe University Medical School, Ankara, Turkey.

Leukocyte adhesion deficiency type I is a rare primary immunodeficiency disorder characterized by mutations in the ITGB2 gene encoding CD18. We present clinical and immunological features of 15 patients with leukocyte adhesion deficiency type 1 (LAD-1). Targeted next-generation sequencing was performed with either a primary immunodeficiency gene panel comprising 266 genes or a small LAD-panel consisting of five genes for genetic analysis. To measure the expression level of integrins on the leukocyte surface, flow cytometry analysis was performed. The median age of the patients at diagnosis was 3 (1-48) months. Eleven (73%) of the 15 patients had a LAD-1 diagnosis in their first 6 months and 14 (93%) patients had consanguineous parents. Delayed separation of the umbilical cord was present in 80% (n = 12) of the patients in our cohort, whereas omphalitis was observed in 53% (n = 8) of the patients. Leukocytosis with neutrophil predominance was observed in 73% (n = 11) patients. Nine distinct variants in the ITGB2 gene in 13 of the 15 patients with LAD-1 were characterized, two of which (c.305_306delAA and c.779_786dup) are novel homozygous mutations of ITGB2. Four unrelated patients from Syria had a novel c.305_306delAA mutation that might be a founder effect for patients of Syrian origin. Four (27%) patients underwent hematopoietic stem cell transplantation. Two patients died because of HSCT complications and the other two are alive and well. Early differential diagnosis of the patients is critical in the management of the disease and genetic evaluation provides a basis for family studies and genetic counseling.
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http://dx.doi.org/10.1111/cei.13645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446394PMC
October 2021

Infliximab therapy in an infant with Netherton syndrome.

Pediatr Dermatol 2021 May 22;38(3):714-716. Epub 2021 Apr 22.

Division of Pedaiatric Immunology, Uludag University Faculty of Medicine, Bursa, Turkey.

We present a patient with Netherton syndrome and severe skin manifestations treated with infliximab. By 6 months of age, the child had intractable pruritus, scaling, dry skin, and generalized eczematous lesions resistant to conventional therapies for atopic dermatitis. Clinical improvement was observed following the third infusion of infliximab, and by 12 months of age, the skin lesions completely resolved. Infliximab is a promising option for the management of skin inflammation in Netherton syndrome, even in infants.
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http://dx.doi.org/10.1111/pde.14590DOI Listing
May 2021

Proven Food-Induced Acute Urticaria and Predictive Factors for Definitive Diagnosis in Childhood.

Int Arch Allergy Immunol 2021 18;182(7):607-614. Epub 2021 Feb 18.

Pediatric Allergy and Immunology Department, Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Background: Urticaria can be the only sign of a food allergy or can be seen together with other signs and symptoms of a food allergy.

Objective: To determine the demographic, etiologic, and clinical features of food-induced acute urticaria in childhood.

Methods: Patients suspected of food-induced acute urticaria were included in this prospective cross-sectional multicenter study.

Results: Two hundred twenty-nine urticaria cases were included in this study. Seventeen patients who did not meet the inclusion criteria of the study were excluded. Of the 212 included cases, 179 (84.4%) were diagnosed with definitive food-induced acute urticaria. The most common foods causing acute urticaria were cow's milk, hen's eggs, and nuts in 56.4, 35.2, and 19% of cases, respectively. The positive predictive value of a history of milk-induced acute urticaria together with a milk-specific IgE >5 kU/L for cow's milk-induced acute urticaria was 92% (95% CI: 81-96%). A history of cow's milk-induced and/or hen's egg-induced acute urticaria was consistent with a definitive diagnosis of food-induced urticaria (Chen's kappa: 0.664 and 0.627 for milk and eggs, respectively). Urticaria activity scores were higher in patients with food-induced acute urticaria (p = 0.002).

Conclusion: Cow's milk, hen's eggs, and nuts were the most common allergens in the etiology of childhood food-induced acute urticaria. Although the urticaria activity score provides guidance for diagnosis, an oral food challenge is often essential for the definitive diagnosis of a patient with a history of food-induced acute urticaria.
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http://dx.doi.org/10.1159/000513267DOI Listing
September 2021

Anti-Tumor Necrosis Factor Treatment in the Management of Pediatric Noninfectious Uveitis: Infliximab Versus Adalimumab.

J Ocul Pharmacol Ther 2021 05 28;37(4):236-240. Epub 2021 Jan 28.

Uludag University School of Medicine, Pediatric Immunology and Rheumatology, Bursa, Turkey.

Management of uveitis displays a particular challenge in childhood. This study aims to compare the efficacy and safety of infliximab (IFX) and adalimumab (ADA) in pediatric noninfectious uveitis that were refractory to conventional immunosuppresives. This retrospective single-center study included 33 patients who were treated with anti-tumor necrosis factor (TNF) agents (16 with IFX and 17 with ADA). Patients had diverse etiologies, including juvenile idiopathic arthritis, idiopathic uveitis, and Behçet's disease. Demographic characteristics, systemic diagnosis, findings of the ophthalmological examination, control of ocular inflammation, response to treatment, and the rate of clinical remission were studied. Fourteen (87.5%) patients receiving IFX and 10 (58.8%) patients receiving ADA achieved response to treatment during the follow-up ( = 0.118). The agents were discontinued with complete clinical remission in 6 (37.5%) patients receiving IFX and in 2 (11.8%) patients receiving ADA ( = 0.118). Baseline visual acuities and parameters of inflammation improved significantly in both groups after anti-TNF therapy. Both IFX and ADA are safe and effective for pediatric noninfectious uveitis.
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http://dx.doi.org/10.1089/jop.2020.0081DOI Listing
May 2021

The Impact of the SARS-CoV-2 Pandemic in PID Patients Receiving Ig Replacement Therapy.

J Clin Immunol 2021 05 15;41(4):733-737. Epub 2021 Jan 15.

Department of Pediatrics, Division of Immunology and Rheumatology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey.

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http://dx.doi.org/10.1007/s10875-020-00958-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810283PMC
May 2021

Rituximab Therapy for Recalcitrant Idiopathic Sclerosing Orbital Inflammation.

Ophthalmic Plast Reconstr Surg 2021 May-Jun 01;37(3):e91-e97

Departments of Immunology.

Three patients (3 female patients; aged 7, 35, and 61 years) who had recalcitrant idiopathic sclerosing orbital inflammation were treated with rituximab. The disease was bilateral in 1 patient (4 orbits in total): diffuse in 2 and localized in 2 orbits. It caused optic neuropathy in 1 orbit of each patient. Conventional immunotherapy and tumor debulking surgery were unsuccessful in controlling the disease. After rituximab infusions (375 mg/m2/week for 4 weeks), all patients improved symptomatically. Radiologically, the local lesions resolved completely and diffuse lesions partially. Two patients with recurrent inflammation during follow up (78, 58, and 51 months) responded well to immediate, short-term steroid treatments. Short-term rituximab therapy can induce effective remissions in patients with refractory idiopathic sclerosing orbital inflammation. Early and local lesions may respond better to treatment than diffuse lesions. Nevertheless, inflammatory exacerbations can occur during late follow up.
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http://dx.doi.org/10.1097/IOP.0000000000001843DOI Listing
May 2021

Evaluation of pulmonary findings in patients with humoral immunodeficiency.

Turk Pediatri Ars 2020 19;55(2):174-183. Epub 2020 Jun 19.

Division of Pediatric Allergy and Immunology, Department of Pediatrics, Uludağ University, Faculty of Medicine, Bursa, Turkey.

Aim: To determine the frequency of sinopulmonary infections, detect changes in the respiratory system, and measure functional capacity of the lungs in our patients with humoral immunodeficiency.

Material And Methods: Fifty-six patients with humoral immunodeficiency were enrolled in this study. The clinical, laboratory, and radiologic data, and pulmonary function tests of the subjects were evaluated from their file records, retrospectively.

Results: The distribution of our patients was as follows: 25 patients had common variable immune deficiency, three patients had X-linked agammaglobulinemia, five patients had hyper immunoglobulin M syndrome, 19 patients had deficiency of immunoglobulin G subset, and four patients had selective immunoglobulin A deficiency. The most common symptom of the patients was chronic cough (n=47, 83.9%). The most common pathologies on high-resolution computed tomography of the chest were atelectasis and bronchiectasis (27.7%). The most common pathology in pulmonary function tests was the presence of moderate obstructive patterns along with restrictive patterns (n=6,12.5%). The FEV 1, FVC, and FEF 25-75 values were significantly lower in patients with common variable immunodeficiency compared with the patients who had IgG subset deficiencies (p=0.001, p=0.01, p=0.01). Among the patients who were treated with intravenous immunoglobulin, the age at the diagnosis of immunodeficiency was higher in patients with bronchiectasis (14.2±8.4 years) compared with those without bronchiectasis (10.1±11.4 years) (p=0.04).

Conclusion: Clinical findings are not sufficient to monitor the structural and functional changes in the respiratory system, and patients should be evaluated using high-resolution computed tomography of the chest and pulmonary function tests.
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http://dx.doi.org/10.14744/TurkPediatriArs.2020.46656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344133PMC
June 2020

Patients eligible for modulator drugs: Data from cystic fibrosis registry of Turkey.

Pediatr Pulmonol 2020 09 26;55(9):2302-2306. Epub 2020 May 26.

Division of Pediatric Allergy and Immunology, Faculty of Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey.

Background: A better understanding of cystic fibrosis transmembrane conductance regulator biology has led to the development of modulator drugs such as ivacaftor, lumacaftor-ivacaftor, tezacaftor-ivacaftor, and elexacaftor-tezacaftor-ivacaftor. This cross-sectional study evaluated cystic fibrosis (CF) patients eligible for modulator drugs.

Methods: Data for age and genetic mutations from the Cystic Fibrosis Registry of Turkey collected in 2018 were used to find out the number of patients who are eligible for modulator therapy.

Results: Of registered 1488 CF patients, genetic analysis was done for 1351. The numbers and percentages of patients and names of the drugs, that the patients are eligible for, are as follows: 122 (9.03%) for ivacaftor, 156 (11.54%) for lumacaftor-ivacaftor, 163 (11.23%) for tezacaftor-ivacaftor, and 57 (4.21%) for elexacaftor-tezacaftor-ivacaftor. Among 1351 genotyped patients total of 313 (23.16%) patients are eligible for currently licensed modulator therapies (55 patients were shared by ivacaftor and tezacaftor-ivacaftor, 108 patients were shared by lumacaftor-ivacaftor and tezacaftor-ivacaftor, and 22 patients were shared by tezacaftor-ivacaftor and elexacaftor-tezacaftor-ivacaftor groups).

Conclusions: The present study shows that approximately one-fourth of the registered CF patients in Turkey are eligible for modulator drugs. As, frequent mutations that CF patients have in Turkey are different from North American and European CF patients, developing modulator drugs effective for those mutations is necessary. Furthermore, as modulator drugs are very expensive currently, financial support of the government in developing countries like Turkey is noteworthy.
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http://dx.doi.org/10.1002/ppul.24854DOI Listing
September 2020

Mutational landscape of severe combined immunodeficiency patients from Turkey.

Int J Immunogenet 2020 Dec 22;47(6):529-538. Epub 2020 May 22.

Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.

Severe combined immunodeficiency (SCID) has a diverse genetic aetiology, where a clinical phenotype, caused by single and/or multiple gene variants, can give rise to multiple presentations. The advent of next-generation sequencing (NGS) has recently enabled rapid identification of the molecular aetiology of SCID, which is crucial for prognosis and treatment strategies. We sought to identify the genetic aetiology of various phenotypes of SCIDs and assessed both clinical and immunologic characteristics associated with gene variants. An amplicon-based targeted NGS panel, which contained 18 most common SCID-related genes, was contumely made to screen the patients (n = 38) with typical SCID, atypical SCID or OMENN syndrome. Allelic segregations were confirmed for the detected gene variants within the families. In total, 24 disease-causing variants (17 known and 7 novel) were identified in 23 patients in 9 different SCID genes: RAG1 (n = 5), RAG2 (n = 2), ADA (n = 3), DCLRE1C (n = 2), NHEJ1 (n = 2), CD3E (n = 2), IL2RG (n = 3), JAK3 (n = 4) and IL7R (n = 1). The overall success rate of our custom-made NGS panel was 60% (39.3% for NK+ SCID and 100% for NK- SCID). Incidence of autosomal-recessive inherited genes is more frequently found in our cohort than the previously reported populations probably due to the high consanguineous marriages in Turkey. In conclusion, the custom-made sequencing panel was able to identify and confirm the previously known and novel disease-causing variants with high accuracy.
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http://dx.doi.org/10.1111/iji.12496DOI Listing
December 2020

Clinical features and accompanying findings of Pseudo-Bartter Syndrome in cystic fibrosis.

Pediatr Pulmonol 2020 08 4;55(8):2011-2016. Epub 2020 May 4.

Department of Pediatric Pulmonology, Ankara Children's Hematology Oncology Training and Research Hospital, Ankara, Turkey.

Background: Pseudo-Bartter syndrome (PBS) is a rare complication of cystic fibrosis (CF) and there are limited data in the literature about it. We aimed to compare clinical features and accompanying findings of patients with PBS in a large patient population.

Methods: The data were collected from the Cystic Fibrosis Registry of Turkey where 1170 CF patients were recorded in 2017. Clinical features, diagnostic test results, colonization status, complications, and genetic test results were compared in patients with and without PBS.

Results: Totally 1170 patients were recorded into the registry in 2017 and 120 (10%) of them had PBS. The mean age of diagnosis and current age of patients were significantly younger and newborn screening positivity was lower in patients with PBS (P < .001). There were no differences between the groups in terms of colonization status, mean z-scores of weight, height, BMI, and mean FEV percentage. Types of genetic mutations did not differ between the two groups. Accompanying complications were more frequent in patients without PBS.

Conclusion: PBS was detected as the most common complication in the registry. It could be due to warm weather conditions of our country. It is usually seen in younger ages regardless of mutation phenotype and it could be a clue for early diagnosis of CF.
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http://dx.doi.org/10.1002/ppul.24805DOI Listing
August 2020

Three different faces of TACI mutations.

Scand J Immunol 2020 06 7;91(6):e12879. Epub 2020 Apr 7.

Division of Pediatric Allergy and Clinical Immunology, Uludag University Faculty of Medicine, Bursa, Turkey.

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http://dx.doi.org/10.1111/sji.12879DOI Listing
June 2020

The evaluation of malignancies in Turkish primary immunodeficiency patients; a multicenter study.

Pediatr Allergy Immunol 2020 07 9;31(5):528-536. Epub 2020 Mar 9.

Division of Pediatric Allergy and Clinical Immunology, Uludag University Faculty of Medicine, Bursa, Turkey.

Background: There are no data regarding the prevalence of malignancies in patients with primary immunodeficiency (PID) in Turkey. Along with the prevalence of malignancy, we aimed to present the types of malignancy and define the underlying immune deficiency of the patients.

Method: Between the years 1992 and 2018, from five tertiary immunology clinics, fifty-nine patients with PID who developed malignancy were included. All patients were evaluated for demographics, clinical features, and prognosis.

Results: The prevalence of malignancy in our cohort was detected as 0.9% (59/6392). The male-to-female ratio was 1.8 (38/21), and the median age of patients was 14 years (range: 1.5-51). The median age at diagnosis of malignancy was 10 years (range: 1.5-51). Ataxia-telangiectasia was the most frequent PID in patients with malignancy (n = 19, 32.2%), and non-Hodgkin lymphoma was the most common malignancy (n = 32, 51.6%). The rate of malignancy in DOCK8 deficiency (n = 7/43, 16.3%) was higher than AT (n = 19/193, 9.8%), Wiskott-Aldrich syndrome (n = 2/22, 9.1%), and common variable immunodeficiency (n = 11/205, 5.4%). EBV quantitative PCR was positive in 16 out of 53 patients (30.2%). Three patients had secondary malignancies. Remission was achieved in 26 patients (44.1%). However, 31 patients (52.5%) died. Two patients (3.4%) are still on chemotherapy.

Conclusion: This study is the largest cohort investigating the association of malignancy in patients with PID in Turkey. While lymphoid malignancies were the most common malignancy and observed more frequently in AT patients, the risk for malignancy was higher in patients with DOCK8 deficiency compared to AT.
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http://dx.doi.org/10.1111/pai.13231DOI Listing
July 2020

Cystic fibrosis in Turkey: First data from the national registry.

Pediatr Pulmonol 2020 02 11;55(2):541-548. Epub 2019 Nov 11.

Division of Pediatric Pulmonology, Ankara Children's Hematology Oncology Training and Research Hospital, Ankara, Turkey.

Background: Cystic fibrosis (CF) care has been implemented in Turkey for a long time; however, there had been no patient registry. For this purpose, the Turkish National CF Registry was established. We present the first results of registry using data collected in 2017.

Methods: The data were collected using a data-entry software system, which was accessed from the internet. Demographic and annually recorded data consisted of 15 and 79 variables, respectively.

Results: There were 1170 patients registered from 23 centers; the estimated coverage rate was 30%. The median age at diagnosis was 1.7 years (median current age: 7.3 years); 51 (4.6%) patients were aged over 18 years. Among 293 patients who were under 3 years of age, 240 patients (81.9%) were diagnosed through newborn screening. Meconium ileus was detected in 65 (5.5%) patients. Genotyping was performed in 978 (87.4%) patients and 246 (25.2%) patients' mutations were unidentified. The most common mutation was deltaF508 with an allelic frequency of 28%, followed by N1303K (4.9%). The median FEV1% predicted was 86. Chronic colonization with Pseudomonas aeruginosa was seen in 245 patients. The most common complication was pseudo-Bartter syndrome in 120 patients. The median age of death was 13.5 years in a total of 15 patients.

Conclusions: Low coverage rate, lack of genotyping, unidentified mutations, and missing data of lung functions are some of our greatest challenges. Including data of all centers and reducing missing data will provide more accurate data and help to improve the CF care in Turkey in the future.
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http://dx.doi.org/10.1002/ppul.24561DOI Listing
February 2020

Abatacept as a Long-Term Targeted Therapy for LRBA Deficiency.

J Allergy Clin Immunol Pract 2019 Nov - Dec;7(8):2790-2800.e15. Epub 2019 Jun 22.

Division of Pediatric Allergy and Immunology, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey.

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.
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http://dx.doi.org/10.1016/j.jaip.2019.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842687PMC
October 2020

Vedolizumab treatment in a patient with X-linked agammaglobulinemia, is it safe and efficient?

Turk J Pediatr 2019 ;61(6):937-940

Divisions of Pediatric Immunology, Uludağ University Faculty of Medicine, Bursa, Turkey.

Çekiç Ş, Özgür T, Karalı Y, Özkan T, Kılıç SŞ. Vedolizumab treatment in a patient with X-linked agammaglobulinemia, is it safe and efficient? Turk J Pediatr 2019; 61: 937-940. The loss of inflammatory regulation resulting from the absence of B-lymphocytes leads to a risk for autoimmune and autoinflammatory complications. There is no data on the use of Vedolizumab in patients with X-linked agammaglobulinemia (XLA) as well as children with another primary immunodeficiency (PID) diseases. A 4-year-old boy was admitted to our clinic with a history of recurrent respiratory tract infections. He was diagnosed with XLA based on extremely low immunoglobulins, very low level of B cells, genetic mutation of BTK gene, and family history. At the age of 8, he suffered from intermittent fever attacks, abdominal pain, weakness, oral aft, and weight loss. His clinical and laboratory features were consistent with inflammatory bowel disease. Histopathological examination of the biopsy material obtained from terminal ileum, colon and cecum showed Crohn`s disease. Initially, he was treated with prednisolone and infliximab. Because of the lack of response, infliximab treatment was switched to adalimumab. Terminal ileum was resected to relieve obstruction complication. Although he had been treated with adalimumab, a significant improvement was not observed. Vedolizumab (Entyvio™), a humanized monoclonal antibody α4β7 integrin-receptor antagonist, was commenced. After treatment with vedolizumab, his fever and abdominal pain attacks reduced, his total daily calorie intake increased and weight gain improved. He began to walk again and continued his school education properly. No side effects were observed in 18 months. This is the first immunocompromised child treated with vedolizumab. The symptoms of the patient receded and no side effect were seen during the treatment.
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http://dx.doi.org/10.24953/turkjped.2019.06.016DOI Listing
August 2020

Ocular Involvement in Muckle-Wells Syndrome.

Ocul Immunol Inflamm 2020 17;28(1):70-78. Epub 2018 Dec 17.

Pediatric Allergy and Clinical Immunology, Uludag University School of Medicine, Bursa, Turkey.

: To present the ocular findings of the members of a family that has the diagnosis of Muckle Wells syndrome, a form of cryopyrin associated periodic syndrome (CAPS).: Nine patients with MWS were included in this study. Each study participant underwent a systemic evaluation, comprehensive ophthalmic examination, and auxillary testings.: In this study, conjunctivitis was the most prominent ocular finding. Other relatively common ocular findings included band keratopathy, clinical signs of past uveitis, and corneal topography abnormalities. Nystagmus, corneal leukoma, and optic nerve pallor with epiretinal membrane were also detected. Rare ocular manifestations were posterior stromal corneal opacification with edema, anterior iris snychecia, and mild cataract.: MWS is a rare systemic autoinflammatory disorder that presents with a variety of ocular findings. Exacerbation of systemic and ocular findings with cold is a hallmark of the disease.
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http://dx.doi.org/10.1080/09273948.2018.1552305DOI Listing
December 2020

Delayed Puberty and Gonadal Failure in Patients with HAX1 Mutation.

J Clin Immunol 2017 Aug 5;37(6):524-528. Epub 2017 Jul 5.

Division of Pediatric Immunology, Uludag University Faculty of Medicine, Görükle, 16059, Bursa, Turkey.

Purpose: Homozygous mutations in the HAX1 gene cause an autosomal recessive form of severe congenital neutropenia (SCN). There are limited data on cases of gonadal insufficiency that involve the HAX1 gene mutation. We aimed to evaluate the pubertal development and gonadal functions of our patients with a p.Trp44X mutation in the HAX1 gene.

Method: Pubertal development, physical and laboratory findings of one male and seven female patients with HAX1 deficiency were evaluated.

Results: The age of the patients was between 13 and 25 years. All female patients were diagnosed with primary ovarian insufficiency (POI) based on amenorrhea and elevated gonadotropins. The ovary volumes in female patients were determined to be smaller than normal for their age through sonographic studies. Short stature associated with gonadal insufficiency was also observed in three patients.

Conclusion: The HAX1 gene is important for ovarian development, in which a p.Trp44X mutation may cause POI in female patients. It is crucial to follow up and evaluate the gonadal functions of female patients in such cases.
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http://dx.doi.org/10.1007/s10875-017-0412-8DOI Listing
August 2017

Is colchicine more effective to prevent periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis episodes in Mediterranean fever gene variants?

Pediatr Int 2017 Jun 24;59(6):655-660. Epub 2017 Apr 24.

Departments of Pediatric Immunology-Rheumatology, Uludag University Faculty of Medicine, Görükle, Bursa, Turkey.

Background: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is the most frequent repetitive fever syndrome in childhood. It is characterized by fever episodes lasting for approximately 3-6 days, once every 3-8 weeks.

Methods: Clinical and laboratory data for PFAPA syndrome patients between January 2010 and December 2014 followed up at a tertiary pediatric care hospital were reviewed.

Results: Four hundred children (256 male, 144 female; mean age at diagnosis, 4.2 ± 2.2 years), were enrolled in the study. During the episodes, mean leukocyte number was high (12 725/mm ) with predominant neutrophils. The mean number of monocytes was 1256/mm , and 90.2% had monocytosis. Serum amyloid A and C-reactive protein were high in 84.6% and in 77.8% of the patients, respectively. Mediterranean fever (MEFV) gene heterozygous mutation was identified in 57 of the 231 patients (24.7%) in whom genetic analysis had been performed. The most frequent mutation was heterozygous M694V (10%, n = 23). Extension of between-episode interval following prophylaxis was noted in 85% of those on regular colchicine treatment (n = 303). In the colchicine group, between-episode interval was prolonged from 18.8 ± 7.9 days (before colchicine treatment) to 49.5 ± 17.6 days on prophylactic colchicine therapy; also, prophylactic treatment was more effective in reducing episode frequency in patients with MEFV gene variant (n = 54, 96%) than in those without (n = 122, 80%; P = 0.003).

Conclusions: This study has involved the largest number of PFAPA syndrome patients in the literature. It is particularly important to assess and to demonstrate the high rate of response to colchicine prophylaxis in PFAPA syndrome patients, especially those with MEFV variant. On blood screening, neutrophilia associated with monocytosis and low procalcitonin could contribute to diagnosis.
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http://dx.doi.org/10.1111/ped.13265DOI Listing
June 2017

Health-care conditions in elementary schools and teachers' knowledge of childhood asthma.

Paediatr Int Child Health 2016 Feb 9;36(1):64-71. Epub 2014 Sep 9.

Division of Paediatric Allergy.

Background: For the adequate control of asthma in school-age children, it is recommended that teachers, school health personnel and administrators should have sufficient knowledge of how to manage asthma during school hours.

Aim: To investigate asthma health care in elementary schools, and teachers' knowledge of childhood asthma and its management.

Methods: The extent of knowledge of childhood asthma in 2779 teachers in 141 elementary schools (children aged 6-14, grades 1-8) in Bursa, the fourth largest city in Turkey, was evaluated. Section I comprised questions about asthma health-care in schools, Section II teachers' knowledge of the main characteristics of asthma and Section III (Likert Scale) teachers' detailed knowledge of the signs, triggering factors, treatment and general knowledge of asthma.

Results: The findings of Section I demonstrated that the organisation of health-care for asthma in schools was insufficient. Of the teachers questioned, 14·7% were not even aware and only 1% and 9·6% of the teachers had been made aware by school health personnel and school records, respectively, of asthmatic children. Only 27·3% of the teachers stated that they were responsible for the health of an asthmatic child. The majority of teachers (70%) said that asthmatic children could use the medication (e.g. inhalers) themselves. In Section II, there were between 44·1% and 75·5% correct answers, while in Section III this figure ranged from 3·3% to 78·4%. The correct answer rate was 60·4% for Sections II and III combined. The results of Sections II and III showed that the teachers' knowledge of asthma was poor in many respects. Teachers who stated that they had asthma or had first-degree relatives with asthma, or those with 10 or more years' experience provided significantly more correct answers in Sections II and III combined than did those without these characteristics (P<0·001).

Conclusions: There is a need to improve and standardise health care for asthma (asthma management policies) in schools. The implementation of asthma education programmes for teachers and other staff responsible for pupils' health should result in better control of this common disease.
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http://dx.doi.org/10.1179/2046905514Y.0000000150DOI Listing
February 2016

Evaluation of the patients diagnosed with Stevens Johnson syndrome and toxic epidermal necrolysis: a single center experience.

Turk Pediatri Ars 2016 Sep 1;51(3):152-158. Epub 2016 Sep 1.

Division of Pediatric Allergy, Department of Pediatrics, Uludağ University School of Medicine, Bursa, Turkey.

Aim: Stevens Johnson syndrome and toxic epidermal necrolysis are severe acute mucocutaneous diseases. In this study, we evaluated the clinical aspects of Steven Johnson syndrome, toxic epidermal necrolysis and Stevens-Johnson syndrome/toxic epidermal necrolysis overlap patients who admitted to our clinics in the last five years.

Material And Methods: Eleven patients diagnosed as Stevens-Johnson syndrome, toxic epidermal necrolysis and Stevens-Johnson syndrome/toxic epidermal necrolysis overlap in Department of Pediatric Allergy in Uludağ University School of Medicine were included in this study. Clinical findings, laboratory tests and response to treatments were evaluated via electronic files.

Results: Two of the patients had Stevens-Johnson syndrome, four had Stevens-Johnson syndrome/toxic epidermal necrolysis overlap, and five had toxic epidermal necrolysis. The median period for drug usage was 10 days (2-44 days). Herpes simpleks virus IgM antibody was detected two patients. The median healing time was 38 days 26-94 days). Maculopapular eruptions and oral mucositis were seen in all patients. Vesicul or bullae, epidermal detachment and ocular involvement in 10 of patients. Wound care, H1 antihistamine and methyl prednisolon were used in all patients, intravenous immunoglobulin were used in 7 patients and cyclosporine in 1 patient. Sequel lesions developed in 2 of the patients and there was no death.

Conclusion: Anticonvulsants, antibiotics and non steroid anti-inflammatory drugs play a major role in the etiology of Stevens-Johnson syndrome and toxic epidermal necrolysis. Anticonvulsants are associated with severe disease. The patients with proper wound care and treatment with immunosuppressive drugs can be recovered without or with minimal sequelae.
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http://dx.doi.org/10.5152/TurkPediatriArs.2016.3836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5047364PMC
September 2016

Massive ascites in a canakinumab resistant case with MVA leading to bone marrow transplantation.

Rheumatol Int 2016 Jul 10;36(7):1011-3. Epub 2016 Mar 10.

Division of Immunology, Department of Pediatrics, Uludag University Faculty of Medicine, Bursa, Turkey.

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http://dx.doi.org/10.1007/s00296-016-3456-9DOI Listing
July 2016

Juvenile Idiopathic Inflammatory Myopathy in a Patient With Dyskeratosis Congenita Due to C16orf57 Mutation.

J Pediatr Hematol Oncol 2016 Mar;38(2):e75-7

Department of Pediatric Immunology, Uludag University Medical Faculty, Görükle, Bursa, Turkey.

Dyskeratosis congenita (DC) is a rare inherited disorder characterized by reticular skin pigmentation, oral cavity leukoplakia, and nail dystrophy. A variety of noncutaneous (dental, pulmonary, gastrointestinal, neurological, genitourinary, ophthalmic, and skeletal) abnormalities also have been reported. An 8-year-old boy with DC developed juvenile idiopathic inflammatory myopathy. C16orf57 mutation was identified as a genetic cause of DC. Treatment with methylprednisolone was initiated, followed with methotrexate, prednisolone, and high-dose intravenous immunoglobulin treatment. This is the first report on a patient with juvenile idiopathic inflammatory myopathy and DC.
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http://dx.doi.org/10.1097/MPH.0000000000000455DOI Listing
March 2016
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