Person: ÖZEN, AHMET OĞUZHAN
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ÖZEN
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AHMET OĞUZHAN
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Publication Metadata only CHAPLE disease and non-CHAPLE protein losing enteropathies: natural history and immune characteristics(2021-08-01) SELÇUK, MERVE; BARIŞ, SAFA; ÖZEN, AHMET OĞUZHAN; ÖĞÜLÜR, İSMAİL; AYDINER, ELİF; Selcuk M., Sefer A. P., Baser D., Ogulur I., Eltan S. B., Dursun E., Kocamis B., Kasap N., BARIŞ S., AYDINER E., et al.Publication Metadata only Evaluation of a Standardized Bakery Product (SUTMEK) as a Potential Tool for Baked-Milk Tolerance and Immunotherapy Research Studies(KARGER, 2019) ÖZEN, AHMET OĞUZHAN; Kiykim, Ayca; Karakoc-Aydiner, Elif; Gunes, Esra; Nain, Ercan; Ogulur, Ismail; Yazici, Duygu; Aktac, Sule; Bicer, Ayse Humeyra; Sackesen, Cansin; Baris, Safa; Ozen, AhmetBackground and Objectives: About 65-80% of children with IgE-mediated cow's milk allergy (CMA) can tolerate extensively heated milk. We have invested in the mass fabrication of a test product containing milk protein baked at 180 degrees C for 30 min (SUTMEK-milk) and a milk-free placebo (SUTMEK-placebo) to carry out a standardised double-blind placebo-controlled food challenge (DBPCFC) test in patients with CMA. Methods: We studied children with IgE-mediated CMA between 13 and 48 months of age. Specific IgEs (spIgE) to milk proteins were quantified. A DBPCFC with our bakery products was performed, and factors determining reactivity to extensively heated milk were evaluated. We also tested the applicability of SUTMEK products in baked-milk oral immunotherapy in a pilot assessment. Results: We studied 15 children (8 girls, 7 boys) with a median age of 26 months (range: 13-48 months). Nine (60%) patients tolerated a challenge with extensively heated milk, while 6 (40%) were found reactive (anaphylaxis: 2, wheezing: 2, urticaria: 2). spIgE to milk, alpha-lactalbumin, and casein, and the wheal diameter on skin prick testing were higher in the reactive group than the tolerant groups (p = 0.001, p = 0.001, p = 0.002, and p = 0.048, respectively). Receiver-operating characteristic curve analyses yielded the following cut-off values for spIgEs that would predict a reactivity to extensively heated milk; milk: 25 kU/L (area under curve, AUC: 0.981), casein: 32 kU/L (AUC: 0.983), and alpha-lactalbumin: 17 kU/L (AUC: 0.981). Nine patients have tolerated well a continued daily consumption of SUTMEK-milk or -placebo for 6 months at the desired doses. Conclusions: Our bakery products were successfully used in DBPCFC studies and qualified as an acceptable tool for use in the research of interventional tolerance induction. Although spIgE appears useful in determining children at high risk of reacting to extensively heated milk, the predictive cut-off values are still far from being perfect. (c) 2018 S. Karger AG, BaselPublication Metadata only Could Sublingual Immunotherapy Affect Oral Health in Children with Asthma and/or Allergic Rhinitis Sensitized to House Dust Mite?(KARGER, 2017) ÖZEN, AHMET OĞUZHAN; Kiykim, Ayca; Mumcu, Gonca; Ogulur, Ismail; Karakoc-Aydiner, Elif; Direskeneli, Haner; Baris, Safa; Cagan, Hasret; Ozen, AhmetBackground: Sublingual immunotherapy (SLIT) has been successfully employed in IgE-mediated respiratory allergies. However, it is not known whether the modulation of immune responses in the sublingual area during SLIT has any deleterious effect on oral health. We sought to determine the oral health prospectively in children receiving SLIT for house dust mite allergy. Material and Methods: Eighteen children with allergic asthma and/or rhinitis and 31 agematched healthy controls (HC) were included in an openlabeled trial. Oral health was evaluated by scoring the decayed, missing, and filled teeth for primary (dmft) and permanent (DMFT) dentition, and the plaque and gingival indices. Moreover, cariogenic food intake and teeth-brushing habits were also noted at baseline and at 19 months. Results: The mean age of the SLIT participants was 9.5 +/- 3.1 years and that of the HC was 9.2 +/- 3.7 years. The mean duration of SLIT was 19.13 +/- 3.81 months. At baseline, the total dmft and DMFT indices were similar in the SLIT and HC groups (p > 0.05), which demonstrated poor hygiene overall. In the within-group comparisons at the examination at 19 months, the SLIT group had a lower number of carious primary teeth and a higher number of filled primary teeth compared to the count at baseline (p = 0.027 and p = 0.058, respectively). Conclusion: Our study showed no detrimental effect of SLIT on oral health during a period of 19 months of follow-up. Parents should be motivated to use dental health services to prevent new caries formation since our cohort had overall poor oral hygiene at the baseline. (C) 2017 S. Karger AG, BaselPublication Metadata only JAGN1 Deficient Severe Congenital Neutropenia: Two Cases from the Same Family(SPRINGER/PLENUM PUBLISHERS, 2015) ÖZEN, AHMET OĞUZHAN; Baris, S.; Karakoc-Aydiner, E.; Ozen, A.; Delil, K.; Kiykim, A.; Ogulur, I.; Baris, I.; Barlan, I. B.Recently autosomal recessively inherited mutations in the gene encoding Jagunal homolog 1 (JAGN1) was described as a novel disease-causing gene of severe congenital neutropenia (SCN) JAGN1-mutant neutrophils were characterized by abnormality in endoplasmic reticulum structure, absence of granules, abnormal N-glycosylation of proteins and susceptibility to apoptosis. These findings imply the role of JAGN1 in neutrophil survival. Here, we report two siblings with a homozygous mutation in JAGN1 gene, exhibiting multisystemic involvement.Publication Metadata only Basophil activation test for inhalant allergens in pediatric patients with allergic rhinitis(ELSEVIER IRELAND LTD, 2017) ÖZEN, AHMET OĞUZHAN; Ogulur, Ismail; Kiykim, Ayca; Baris, Safa; Ozen, Ahmet; Yuce, Ezgi Gizem; Karakoc-Aydiner, ElifObjective: Flow cytometric quantification of in vitro basophil activation can be quite performant and reliable tool to measure IgE-dependent allergen-specific responses in allergic patients. Current study aimed to evaluate the clinical relevance of basophil activation test (BAT) for the diagnosis of pediatric grass pollen and house dust mite (HDM) allergies. Methods: Forty-seven patients suffering from allergic rhinitis with HDM and grass pollen co sensitization with clinical history of allergic rhinitis and/or asthma and 15 non-allergic healthy subjects were enrolled. BAT was determined by flow cytometry upon double staining with anti-IgE/anti-CD63 mAb. Results: Regarding HDM with cut-off point greater than 12.5% for CD63(+) basophils sensitivity and specificity of the BAT were 90% and 73%, with positive predictive value (PPV) and negative predictive value (NPV) as 0.70 and 0.91, respectively. The analysis of concordance of being either allergic or healthy in comparison to BAT results for HDM revealed a substantial concordance (K index = 0.61, p < 0.001). Grass pollen with cut-off point greater than 11%, BAT attained a sensitivity, specificity, PPV, and NPV of 96%, 93%, 0.98, and 0.88, respectively. The analysis of concordance of being either allergic or healthy in comparison to BAT results for grass pollen revealed an almost perfect concordance (K index = 0.87, p < 0.001). Conclusion: Our findings concluded that BAT is reliable technique in the diagnosis of sensitization to grass pollen and HDM. The sensitivity of BAT in pollen allergic children was found to be remarkably higher in our cohort compared to other studies. (C) 2017 Elsevier B.V. All rights reserved.Publication Metadata only Potentially Beneficial Effect of Hydroxychloroquine in a Patient with a Novel Mutation in Protein Kinase C delta Deficiency(SPRINGER/PLENUM PUBLISHERS, 2015) ÖZEN, AHMET OĞUZHAN; Kiykim, Ayca; Ogulur, Ismail; Baris, Safa; Salzer, Elisabeth; Karakoc-Aydiner, Elif; Ozen, Ahmet Oguzhan; Garncarz, Wojciech; Hirschmugl, Tatjana; Krolo, Ana; Yucelten, Ayse Deniz; Boztug, Kaan; Barlan, Isil B.Protein kinase C delta (PRKCD) has essential functions in controlling B-cell proliferation and apoptosis, development of B-cell tolerance and NK-cell cytolitic activity. Human PRKCD deficiency was recently identified to be causative for an autoimmune lymphoproliferative syndrome like disorder with significant B-cell proliferation particularly of immature B cells. Here we report a child with a novel mutation in PRKCD gene who presented with CMV infection and an early onset SLE-like disorder which was successfully treated with hydroxychloroquine.Publication Metadata only The effect of systemic corticosteroids on the innate and adaptive immune system in children with steroid responsive nephrotic syndrome(SPRINGER, 2016) ÖZEN, AHMET OĞUZHAN; Baris, Hatice Ezgi; Baris, Safa; Karakoc-Aydiner, Elif; Gokce, Ibrahim; Yildiz, Nurdan; Cicekkoku, Dilek; Ogulur, Ismail; Ozen, Ahmet; Alpay, Harika; Barlan, IsilThe severity and duration of immunosuppression caused by corticosteroids (CSs) usage have not been extensively studied. We aimed to investigate the effects of CSs on the various compartments of immune system in relation to timing of initiation and persistence of therapy. Pediatric patients with idiopathic nephrotic syndrome (NS) treated with 2 mg/kg/day prednisolone and healthy control (HC) were enrolled. Blood samples were drawn for immunologic analyses at baseline and at the first and second weeks and first, second, and third months of CS therapy in addition to first and second weeks and first, second, and third months of discontinuation. Fourteen patients (M/F, 7/7) between 1 and 8 years old were evaluated. Untreated NS exhibited high absolute lymphocyte count (ALC)(p = 0.010), absolute CD3(+) T cells (p = 0.020) and absolute CD8(+) T cells (p = 0.006) compared to HC. Suppression in ALC was observed and nadir value was noted at first month of therapy compared to baseline (p = 0.002). The CD4(+) (p = 0.036) and CD8(+) T cell (p = 0.013) counts decreased significantly at the first week of treatment compared to baseline. While baseline B cell counts was indifferent from HC, gradually increased in 2 weeks of CS initiation and decreased during the treatment with a statistical significance compared to HC (p = 0.010). However, after cessation of CS, B cell counts continued to decline and found to be significantly different than baseline at first week (p = 0.008) and at third month (p = 0.040). Conclusion: Apart from baseline lymphocyte subset changing observed in untreated NS patients, our data implies that T cells were suppressed very early in the CS treatment. Interestingly, depressed B cell counts were detected later but persisted even after CS cessation. Due to early decrease in T cells, it would be beneficial to assume the patients as immunosuppressed at the very beginning of CS treatment to avoid infections.Publication Metadata only Parents of ataxia-telangiectasia patients display a distinct cellular immune phenotype mimickingATM-mutated patients(WILEY, 2021) ÖZEN, AHMET OĞUZHAN; Ogulur, Ismail; Ertuzun, Tugce; Kocamis, Burcu; Kendir Demirkol, Yasemin; Uyar, Emel; Kiykim, Ayca; Baser, Dilek; Yesil, Gozde; Akturk, Hacer; Somer, Ayper; Ozen, Ahmet; Karakoc-Aydiner, Elif; Muftuoglu, Meltem; Baris, SafaBackground Heterozygous relatives of ataxia-telangiectasia (AT) patients are at an increased risk for certain AT-related manifestations. We also show that there is an increase of infection frequency in parents of AT patients. Thus, we hypothesized that the parents might exhibit immune alterations similar to their affected children. Methods Lymphocyte phenotyping to enumerate T- and B-cell subsets was performed. Functional analyses included in vitro quantified gamma-H2AX, poly (ADP-ribose) polymerase (PARP) and caspase-9 proteins. Chromosomal instability was determined by comet assay. Results We analyzed 20 AT patients (14F/6M), 31 parents (16F/15M), and 35 age-matched healthy controls. The AT patients' parents exhibited low frequency of naive CD4(+)T- (n = 14, 45%) and recent thymic emigrants (n = 11, 35%) in comparison with the age-matched healthy donors. Interestingly, parents with low naive T cells also demonstrated high rate of recurrent infections (9/14, 64%). In comparison with age-matched controls, parents who had recurrent infections and low naive T cells showed significantly higher baseline gamma-H2AX levels and H2O2-induced DNA damage as well as increased cleaved caspase-9 and PARP proteins. Conclusion Parents of AT patients could present with recurrent infections and display cellular defects that mimic AT patients. The observed immunological changes could be associated with increased DNA double-strand breaks.Publication Metadata only Oxidative Burst with Dihydrorhodamine Test: Reference Values in Healthy Controls(TURKISH SOC IMMUNOLOGY, 2015) ÖZEN, AHMET OĞUZHAN; Cicekkoku, Dilek; Ogulur, Ismail; Karakoc-Aydiner, Elif; Baris, Safa; Kiykim, Ayca; Ozen, Ahmet; Barlan, IstObjectives: In this study, we report reference data of stimulation index (SI) and variation coefficient (VC) data in dihydrorhodamine test in healthy controls. Materials and methods: Two hundred ten healthy controls without primary immunodeficiency warning signs and chronic disease were enrolled in this study. Evaluation was performed in 184 individuals (67 females, 117 males; mean age 9.0 +/- 9.6 years; range 0.3 to 59.2 years) with full data analysis. 2 mL peripheral blood samples were taken from healthy controls and lysis of erythrocytes was provided in flow cytometer tubes. The cells were washed twice with Hank's buffered salt solution (HBSS) and incubated at 37 degrees C for 14 minutes in the 50 ng/mL phorbol myristate acetate (PMA) stimulation. The cells were immediately evaluated using gating granulocytes in the BD FACS Calibur flow cytometer tool. The SI was calculated by dividing the ratio of geometric mean of fluorescence intensities obtained from PMA stimulated neutrophils to non-stimulated values. In flow cytometry, VC values of fluorescence intensity on the x-axis of histogram were obtained in PMA stimulated cells. Results: In the healthy controls, SI values were observed to vary ranging between 20.1 and 125.2 (mean 36.75 +/- 18.3). In the same series, VC values were between 9.9-25.2 (mean 18.2 +/- 3.7). Conclusion: Besides the use of a diagnostic test for chronic granulomatous disease, DHR test is useful in identifying the inheritance type of this disease and carriers. Values presented herein can be used as reference data for the assessment of patients and carriers.