Person: ÖZEN, AHMET OĞUZHAN
Loading...
Email Address
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
ÖZEN
First Name
AHMET OĞUZHAN
Name
39 results
Search Results
Now showing 1 - 10 of 39
Publication Open Access Outcome of Hematopoietic Stem Cell Gene Therapy for Wiskott-Aldrich Syndrome(AMER SOC HEMATOLOGY, 2019-11-13) ÖZEN, AHMET OĞUZHAN; Labrosse, Roxane; Chu, Julia; Armant, Myriam; van der Spek, Jet; Miggelbrink, Alexandra; Fong, Johnson; Everett, John K.; Raymond, Hayley; Kessler, Lyanna; Dansereau, Colleen; Mackinnon, Brenda; Koo, Stephanie; Morris, Emily; London, Wendy B.; Ozen, Ahmet; Baris, Safa; Despotovic, Jenny M.; Forbes, Lisa; Saitoh, Akihiko; Takachi, Takayuki; King, Alejandra; Thi Mai Anh Thi Nguyen; Vy Do Uyen Vu; Bushman, Frederic D.; Galy, Anne; Notarangelo, Luigi; Williams, David A.; Pai, Sung-YunPublication Open Access Immediate adverse reactions to intravenous immunoglobulin in primary immune deficiencies: a single center experience(2020) ÖZEN, AHMET OĞUZHAN; Nain, Ercan; Kıykım, Ayça; Kasap, Nurhan Aruci; Barış, Safa; Özen, Ahmet; Aydıner, Elif KarakoçPublication Open Access Protein Expression in the Diagnosis of LRBA Deficiency by Flow Cytometer(BILIMSEL TIP YAYINEVI, 2017-11-17) ÖZEN, AHMET OĞUZHAN; Ogulur, Ismail; Kiykim, Ayca; Nain, Ercan; Somer, Ayper; Guven, Ayla; Baris, Safa; Ozen, Ahmet; Karakoc Aydiner, ElifObjective: Lipopolysaccharide-responsive beige-like anchor (LRBA) plays a role in cell surface expression of inhibitory cytotoxic T lymphocyte-associated protein-4 (CTLA-4) protein. Recently identified LRBA deficiency leads to immune deficiency and autoimmunity and is diagnosed by mutation analyses and protein expression. Herein, we quantified stimulated and unstimulated intracellular LRBA protein expression by flow cytometry in LRBA deficiency patients. Materials and Methods: Five LRBA deficient patients and seven healthy controls were evaluated. The LRBA expressions were assessed in peripheral-blood-mononuclear-cells in the presence or absence of phorbol-miristat-acetate and ionomycin stimulation. The difference in mean-fluorescence-intensity (Delta MFI) was calculated. Results: The differences in mean-fluorescence-intensity values of LRBA by flow cytometry were 24 +/- 9 for the healthy controls and 4.8 +/- 2.8 for the patients..MFIs were 20.8 for P3, 19 for P4 and 49.6 for healthy controls with stimulants and 4.8, 4.6 and 20.1 respectively without stimulants. Conclusion: As a rapid and widely available assay, flow cytometric assessment of intracellular LRBA expression has been found to be an effective and reliable method in the identification of LRBA deficiency.Publication Open Access Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1(SPRINGER/PLENUM PUBLISHERS, 2016-10) ÖZEN, AHMET OĞUZHAN; Baris, Safa; Alroqi, Fayhan; Kiykim, Ayca; Karakoc-Aydiner, Elif; Ogulur, Ismail; Ozen, Ahmet; Charbonnier, Louis-Marie; Bakir, Mustafa; Boztug, Kaan; Chatila, Talal A.; Barlan, Isil B.Loss and gain-of-function (GOF) mutations in human signal transducer and activator of transcription 1 (STAT1) lead to distinct phenotypes. Although recurrent infections are common to both types of STAT1 mutations, GOF mutations are distinguished by chronic mucocutaneous candidiasis and autoimmunity. However, the clinical spectra of STAT1 GOF mutations continue to expand. We here describe two patients with STAT1 GOF mutations presenting early in life with combined immunodeficiency (CID). Clinical data and laboratory findings including immunophenotyping, level of interferon (IFN)-gamma/IL-17(+) T cells, interferon-induced STAT1 phosphorylation, and JAK inhibitor assays were evaluated. Sequencing of STAT1 gene was performed by Sanger sequencer. Patient 1 (P1) had persistent oral candidiasis and cytomegalovirus (CMV) infection since 2 months of age and later developed cavitary lung lesions due to Mycobacterium tuberculosis. Patient 2 (P2) presented with oral candidiasis and recurrent pneumonia at 4 months of age and subsequently developed CMV pneumonitis. Both patients suffered heterozygous missense mutations in STAT1, leading to deleterious amino acid substitutions in the DNA binding domain (P1: c.1154C > T; p.T385M; P2. c.971G > T; p.C324F). Circulating CD4(+) T cells of both patients exhibited increased interferon-gamma and decreased IL-17 expression as compared to controls. They also exhibited increased IFN-beta and -gamma-induced STAT1 phosphorylation that was reversed upon treatment with the JAK kinase inhibitor ruxolitinib. STAT1 GOF mutations may present early in life with CID, consistent with the clinical heterogeneity of the disease. JAK kinase inhibitors may potentially be useful in some patients as adjunct therapy pending definitive treatment with bone marrow transplantation.Publication Open Access Mucus sialylation determines intestinal host-commensal homeostasis(2022-03-31) ÖZEN, AHMET OĞUZHAN; BARIŞ, SAFA; ERTEM ŞAHİNOĞLU, DENİZ; Yao Y., Kim G., Shafer S., Chen Z., Kubo S., Ji Y., Luo J., Yang W., Perner S. P., Kanellopoulou C., et al.Intestinal mucus forms the first line of defense against bacterial invasion while providing nutrition to support microbial symbiosis. How the host controls mucus barrier integrity and commensalism is unclear. We show that terminal sialylation of glycans on intestinal mucus by ST6GALNAC1 (ST6), the dominant sialyltransferase specifically expressed in goblet cells and induced by microbial pathogen-associated molecular patterns, is essential for mucus integrity and protecting against excessive bacterial proteolytic degradation. Glycoproteomic profiling and biochemical analysis of ST6 mutations identified in patients show that decreased sialylation causes defective mucus proteins and congenital inflammatory bowel disease (IBD). Mice harboring a patient ST6 mutation have compromised mucus barriers, dysbiosis, and susceptibility to intestinal inflammation. Based on our understanding of the ST6 regulatory network, we show that treatment with sialylated mucin or a Foxo3 inhibitor can ameliorate IBD.Publication Open Access A boy with a novel homozygous ZAP70 mutation presenting with a dermatological phenotype and postnatal decrease in CD8(+) T cells(2022-03-01) AYDINER, ELİF; ÖZEN, AHMET OĞUZHAN; BARIŞ, SAFA; Babayeva R., Mongellaz C., Karakus I. S., Cansever M., Bilgic Eltan S., Catak M. C., Bulutoglu A., Kendir Demirkol Y., Eser M., Karakoc-Aydiner E., et al.Patients with deficiency of zeta-chain-associated protein kinase 70 (ZAP-70) protein generally present as combined immunodeficiency (CID) with severe recurrent infections and dermatological findings during the first years of life. They also suffer from diarrhea, mainly resulting from viral agents, lymphoproliferation, and autoimmunity (autoimmune cytopenia, bullous pemphigoid, nephrotic syndrome, and adrenal insufficiency). The most striking immunological findings are severely decreased CD3+CD8+ T-cell counts with decreased proliferation. The current definitive treatment of ZAP-70 deficiency is hematopoietic stem cell transplantation (HSCT).1 To date, 52 patients with biallelic mutations in the ZAP70 gene have been described in the literature.1,2 Herein, we report a patient with a novel missense mutation in the ZAP70 who presented with atypical skin lesions and a rapid decrease in CD8+ T-cell counts on immunological evaluations between 6 and 9 months of age. Despite undetectable ZAP-70 protein, the patient did not present severe infections in the first year of life. This description expands the spectrum of disease caused by mutations in thePublication Open Access Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study(MOSBY-ELSEVIER, 2018-03) ÖZEN, AHMET OĞUZHAN; Barzaghi, Federica; Hernandez, Laura Cristina Amaya; Neven, Benedicte; Ricci, Silvia; Kucuk, Zeynep Yesim; Bleesing, Jack J.; Nademi, Zohreh; Slatter, Mary Anne; Ulloa, Erlinda Rose; Shcherbina, Anna; Roppelt, Anna; Worth, Austen; Silva, Juliana; Aiuti, Alessandro; Murguia-Favela, Luis; Speckmann, Carsten; Carneiro-Sampaio, Magda; Fernandes, Juliana Folloni; Baris, Safa; Ozen, Ahmet; Karakoc-Aydiner, Elif; Kiykim, Ayca; Schulz, Ansgar; Steinmann, Sandra; Notarangelo, Lucia Dora; Gambineri, Eleonora; Lionetti, Paolo; Shearer, William Thomas; Forbes, Lisa R.; Martinez, Caridad; Moshous, Despina; Blanche, Stephane; Fisher, Alain; Ruemmele, Frank M.; Tissandier, Come; Ouachee-Chardin, Marie; Rieux-Laucat, Frederic; Cavazzana, Marina; Qasim, Waseem; Lucarelli, Barbarella; Albert, Michael H.; Kobayashi, Ichiro; Alonso, Laura; De Heredia, Cristina Diaz; Kanegane, Hirokazu; Lawitschka, Anita; Seo, Jong Jin; Gonzalez-Vicent, Marta; Diaz, Miguel Angel; Goyal, Rakesh Kumar; Sauer, Martin G.; Yesilipek, Akif; Kim, Minsoo; Yilmaz-Demirdag, Yesim; Bhatia, Monica; Khlevner, Julie; Padilla, Erick J. Richmond; Martino, Silvana; Montin, Davide; Neth, Olaf; Molinos-Quintana, Agueda; Valverde-Fernandez, Justo; Broides, Arnon; Pinsk, Vered; Ballauf, Antje; Haerynck, Filomeen; Bordon, Victoria; Dhooge, Catharina; Garcia-Lloret, Maria Laura; Bredius, Robbert G.; Kalwak, Krzysztof; Haddad, Elie; Seidel, Markus Gerhard; Duckers, Gregor; Pai, Sung-Yun; Dvorak, Christopher C.; Ehl, Stephan; Locatelli, Franco; Goldman, Frederick; Gennery, Andrew Richard; Cowan, Mort J.; Roncarolo, Maria-Grazia; Bacchetta, RosaBackground: Immunodysregulation polyendocrinopathy enteropathy x-linked(IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. Objective: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. Methods: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. Results: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n 5 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. Conclusions: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term.disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.Publication 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 Open Access A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity(AMER ASSOC ADVANCEMENT SCIENCE, 2018-06-08) ÖZEN, AHMET OĞUZHAN; Beziat, Vivien; Li, Juan; Lin, Jian-Xin; Ma, Cindy S.; Li, Peng; Bousfiha, Aziz; Pellier, Isabelle; Zoghi, Samaneh; Baris, Safa; Keles, Sevgi; Gray, Paul; Du, Ning; Wang, Yi; Zerbib, Yoann; Levy, Romain; Leclercq, Thibaut; About, Fredegonde; Lim, Ai Ing; Rao, Geetha; Payne, Kathryn; Pelham, Simon J.; Avery, Danielle T.; Deenick, Elissa K.; Pillay, Bethany; Chou, Janet; Guery, Romain; Belkadi, Aziz; Guerin, Antoine; Migaud, Melanie; Rattina, Vimel; Ailal, Fatima; Benhsaien, Ibtihal; Bouaziz, Matthieu; Habib, Tanwir; Chaussabel, Damien; Marr, Nico; El-Benna, Jamel; Grimbacher, Bodo; Wargon, Orli; Bustamante, Jacinta; Boisson, Bertrand; Mueller-Fleckenstein, Ingrid; Fleckenstein, Bernhard; Chandesris, Marie-Olivia; Titeux, Matthias; Fraitag, Sylvie; Alyanakian, Marie-Alexandra; Leruez-Ville, Marianne; Picard, Capucine; Meyts, Isabelle; Di Santo, James P.; Hovnanian, Alain; Somer, Ayper; Ozen, Ahmet; Rezaei, Nima; Chatila, Talal A.; Abel, Laurent; Leonard, Warren J.; Tangye, Stuart G.; Puel, Anne; Casanova, Jean-LaurentHeterozygosity for human signal transducer and activator of transcription 3 (STAT3) dominant-negative (DN) mutations underlies an autosomal dominant form of hyper-immunoglobulin E syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341. ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including the STAT3 promoter. The patients' cells have low basal levels of STAT3 mRNA and protein. The autoinduction of STAT3 production, activation, and function by STAT3-activating cytokines is strongly impaired. Like patients with STAT3 DN mutations, ZNF341-deficient patients lack T helper 17 (T(H)17) cells, have an excess of T(H)2 cells, and have low memory B cells due to the tight dependence of STAT3 activity on ZNF341 in lymphocytes. Their milder extra-hematopoietic manifestations and stronger inflammatory responses reflect the lower ZNF341 dependence of STAT3 activity in other cell types. Human ZNF341 is essential for the STAT3 transcription-dependent autoinduction and sustained activity of STAT3.Publication Open Access Genomic Spectrum and Phenotypic Heterogeneity of Human IL-21 Receptor Deficiency(SPRINGER/PLENUM PUBLISHERS, 2021-08) ÖZEN, AHMET OĞUZHAN; Cagdas, Deniz; Mayr, Daniel; Baris, Safa; Worley, Lisa; Langley, David B.; Metin, Ayse; Aytekin, Elif Soyak; Atan, Raziye; Kasap, Nurhan; Bal, Sevgi Koestel; Dmytrus, Jasmin; Heredia, Raul Jimenez; Karasu, Gulsun; Torun, Selda Hancerli; Toyran, Muge; Karakoc-Aydiner, Elif; Christ, Daniel; Kuskonmaz, Baris; Uckan-Cetinkaya, Duygu; Uner, Aysegul; Oberndorfer, Felicitas; Schiefer, Ana-Iris; Uzel, Gulbu; Deenick, Elissa K.; Keller, Baerbel; Warnatz, Klaus; Neven, Benedicte; Durandy, Anne; Sanal, Ozden; Ma, Cindy S.; Ozen, Ahmet; Stepensky, Polina; Tezcan, Ilhan; Boztug, Kaan; Tangye, Stuart G.Biallelic inactivating mutations in IL21R causes a combined immunodeficiency that is often complicated by cryptosporidium infections. While eight IL-21R-deficient patients have been reported previously, the natural course, immune characteristics of disease, and response to hematopoietic stem cell transplantation (HSCT) remain to be comprehensively examined. In our study, we have collected clinical histories of 13 patients with IL-21R deficiency from eight families across seven centers worldwide, including five novel patients identified by exome or NGS panel sequencing. Eight unique mutations in IL21R were identified in these patients, including two novel mutations. Median age at disease onset was 2.5 years (0.5-7 years). The main clinical manifestations were recurrent bacterial (84.6%), fungal (46.2%), and viral (38.5%) infections; cryptosporidiosis-associated cholangitis (46.2%); and asthma (23.1%). Inflammatory skin diseases (15.3%) and recurrent anaphylaxis (7.9%) constitute novel phenotypes of this combined immunodeficiency. Most patients exhibited hypogammaglobulinemia and reduced proportions of memory B cells, circulating T follicular helper cells, MAIT cells and terminally differentiated NK cells. However, IgE levels were elevated in 50% of IL-21R-deficient patients. Overall survival following HSCT (6 patients, mean follow-up 1.8 year) was 33.3%, with pre-existing organ damage constituting a negative prognostic factor. Mortality of non-transplanted patients (n = 7) was 57.1%. Our detailed analysis of the largest cohort of IL-21R-deficient patients to date provides in-depth clinical, immunological and immunophenotypic features of these patients, thereby establishing critical non-redundant functions of IL-21/IL-21R signaling in lymphocyte differentiation, humoral immunity and host defense against infection, and mechanisms of disease pathogenesis due to IL-21R deficiency. Outcome following HSCT depends on prior chronic infections and organ damage, which should thus be considered as early as possible following molecular diagnosis.