Person: ÖĞÜLÜR, İSMAİL
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ÖĞÜLÜR
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İSMAİL
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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 Open Access The Diagnostic Value of Flow Cytometry in DOCK8 Deficiency(TURKISH SOC IMMUNOLOGY, 2019) ÖZEN, AHMET OĞUZHAN; Ogulur, Ismail; Kiykim, Ayca; Nain, Ercan; Kasap, Nurhan; Akgun, Gamze; Karakoc-Aydiner, Elif; Ozen, Ahmet; Baris, SafaIntroduction: DOCK8 deficiency is a combined immunodeficiency with severe eczema, food allergy and autoimmunity. Early diagnosis is important for the treatment of patients. In this study, diagnostic value of flow cytometric detection of DOCK8 protein expression was evaluated in patients with DOCK8 deficiency. Material and Methods: Seven patients with DOCK8 deficiency and 20 healthy controls were enrolled in the study. Peripheral blood mononuclear cells (PBMCs) were isolated from patients and healthy controls, and DOCK8 protein expressions were detected. The data were analyzed as raw mean fluorescein intensity (MFI) and difference in MFI (Delta MFI) between cells stained in patients and healthy controls with and-DOCK8 antibody and isotype control. As the experiments were done on different days, the Delta MPI values obtained were normalized according to the current healthy control values and percent values were calculated. Results: The median age of DOCK8 patients was 12 years (8-15). Six of the patients have large deletions and 1 has a missense mutation in DOCK8 gene. Raw MFI values (p=0.0008) and normalized Delta MFI-percent values (p<0.0001) were significantly lower in DOCK8 patients compared to healthy controls. The patient with missense mutation had a raw MFI value close to the control (patient MFI: 23.70, control MFI: 35.50). Median of raw MFI was 4.95 (3.65-5.67) in patients and 26.2 (21.6-32.1) in healthy controls. Conclusion: Flow cytometric detection of DOCK8 protein is very important for the diagnosis of DOCK8 deficiency since the deletion mutations cause almost complete loss of DOCK8 protein expression, while patients with missense mutations could have nearly normal levels of protein, and this can lead to the underestimation of the diagnosis. Therefore, flow cytometric detection is an adjunct method for the diagnosis of DOCK8 disease, and genetic analysis should be offered to all suspicious cases.Publication 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 Lymphocyte proliferation in common variable immunodeficiency (CVID) patients by carboxyfluorescein succinimidyl ester (CFSE)(2011-01-01) AKKOÇ, TUNÇ; ÖĞÜLÜR, İSMAİL; AYDINER, ELİF; BARIŞ, SAFA; Izgi A., AKKOÇ T., Ogulur I., Tevetoglu A., AYDINER E., BARIŞ S., Bahceciler N., Barlan I.Objective: Common variable immunodeficiency (CVID) is a heterogeneous disease in the group of predominantly antibody deficiencies, which is defined by hypogammaglobulinemia and normal or low level of B cells, and characterized by increased susceptibility to recurrent bacterial infections, autoimmune disorders, and malignancies. In this study, we aimed to investigate the proliferation of the B and T lymphocytes in patients with CVID.Publication Open Access Diagnostic Usage of Intracellular Protein Staining by Flow Cytometer in Primary Immune Deficiencies; Marmara Experience(BILIMSEL TIP YAYINEVI, 2018-01-10) ÖZEN, AHMET OĞUZHAN; Ogulur, Ismail; Baris, Safa; Ozen, Ahmet; Nain, Ercan; Kiykim, Ayca; Karakoc-Aydiner, ElifObjective: The aim of our study was the optimization and standardization of intracellular dedicator of cytokinesis 8 (DOCK8), LPS-responsive beige-like anchor protein (LRBA), SH2D1A/SLAM-ssociated protein (SAP) and X-linked inhibitor of apoptosis protein (XIAP) protein expressions in healthy controls with a single flow cytometer protocol and to concomitantly evaluate the possible use of this method for diagnosis. Materials and Methods: Peripheral blood mononuclear cells were isolated from heparinized blood samples. Protein expressions were analyzed as mean fluorescein intensity difference (Delta MFI) according to the isotype. Results: Delta MFI values obtained by DOCK8 antibody staining were 21.3 +/- 4 in CD3+ T cells and 25 +/- 3.3 in CD20+ T cells in healthy controls. These values in patients with DOCK8 deficiency were either very low or completely absent. Delta MFI values obtained by LRBA protein antibody staining were 36 +/- 7.7 in healthy controls, while they were at the very low levels of 5.9 +/- 1.8 in the LRBA protein deficiency patients. The values obtained by SAP and XIAP antibody staining were 30.2 +/- 3 in CD8+ T cells for SAP, 13.9 +/- 3.2 in CD3+ T and 14.6 +/- 3.5 in CD20+ B cells for XIAP. Since the SAP and XIAP results were not confirmed by gene sequencing, the results were not compared to healthy controls. Conclusion: Due to its rapid and reliable results in clinically relevant cases for DOCK8 and LRBA deficiencies, analysis of protein expression is primarily suitable to evaluate intracellular staining protocol by flow cytometer. In addition, this particular method could be suitable for patients considered to be SAP and XIAP deficient.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.