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ÖZEN, AHMET OĞUZHAN

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ÖZEN

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AHMET OĞUZHAN

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    Lymphocyte Subset Abnormalities in Pediatric-Onset Common Variable Immunodeficiency
    (KARGER, 2020) ÖZEN, AHMET OĞUZHAN; Ogulur, Ismail; Kiykim, Ayca; Baser, Dilek; Karakoc-Aydiner, Elif; Ozen, Ahmet; Baris, Safa
    Introduction: Common variable immunodeficiency (CVID) is characterized by recurrent infections, autoimmunity, lymphoproliferation, hypogammaglobulinemia, and defective antibody production. In CVID, B-cell abnormalities were described to predict end organ involvement and prognosis. Pediatric-onset CVID is much rarer than adult CVID, and lymphocyte subset abnormalities have not been thoroughly evaluated. Objective: We sought to determine lymphocyte subset abnormalities and their association with end organ involvement in pediatric-onset CVID patients. Methods: The clinical manifestations and laboratory findings including absolute numbers and percentages of B-, T-, and NK cell populations were assessed in pediatric-onset CVID patients and compared to age-matched healthy controls. The patients were divided into 2 groups according to age at assessment (pediatric CVID patients: 10-16 years, n = 9; and adult CVID patients: >16 years, n = 13). The comparisons between lymphocyte subsets and organ involvement were also evaluated. Results: Mean age at symptom onset was 18 (3-204) months. All CVID patients with pediatric onset had decreased levels of total and memory B cells, CD4(+) T cells, CD4(+)CD45RA(+) naive T cells, and recent thymic emigrant (RTE) cells. On the other hand, they had increases in CD8(+)CD45RO(+) memory T cells. Interestingly, adult CVID patients demonstrated high frequencies of activated and double-negative T cells, which were unique only for this group of patients. Specific cellular abnormalities associated with the reduction in B and NK cells and increase in CD8(+) T cells were found in patients with bronchiectasis. Moreover, in pediatric CVID patients, low serum IgA levels and decreased numbers of naive T and RTE cells were determined as risk factors for chronic diarrhea. Conclusions: Specific abnormalities in B- and T-lymphocyte compartments were identified in pediatric-onset CVID patients and appear to be associated with end organ manifestations.
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    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, Safa
    Background 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.
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    Evaluation of Hyperimmunoglobulin M Syndrome by Flow Cytometry
    (TURKISH SOC IMMUNOLOGY, 2015) ÖZEN, AHMET OĞUZHAN; Cinar, Suzan; Gelmez, Metin Yusuf; Baris, Safa; Aydiner, Elif Karakoc; Ozen, Ahmet Oguzhan; Akturk, Hacer; Barlan, Isil; Camcioglu, Yildiz; Deniz, Gunnur
    Objectives: In this study, we discuss CD40 and CD40L expression findings in hyperimmunoglobuline M (HIGM) syndrome suspected patients obtained by flow cytometry. Patients and methods: Between May 2009 and February 2014, CD40 analysis was performed in 12 male (range, 4 months to 20 years) and eight female patients (range, 2 months to 28 years) and CD40 ligand (CD40L) analysis in eight male patients (range, 11 months to 20 years). Peripheral blood mononuclear cell (PBMC) samples were stained with anti-CD19, -CD45, -CD20 and -CD40 monoclonal antibodies and CD19(+)CD40(+) cells were detected in the flow cytometer. For the diagnosis of X-linked HIGM syndrome, isolated PBMCs were cultured in phorbol myristate acetate and ionomycin for four hours and then CD3(+)CD4(+)CD8(-)CD40L(+) cells were analyzed by flow cytometry. Results: Compared to the healthy controls, low CD40 expression in one female patient (0.09%) and low CD40L expression in three male patients (0.03%, 2.7% and 4%, respectively) were observed. Conclusion: Although flow cytometry is a quick and reliable method in the diagnosis of HIGM syndrome, additional genetic testing is required to establish the definite diagnosis.