Person: AYDINER, ELİF
Loading...
Email Address
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
AYDINER
First Name
ELİF
Name
4 results
Search Results
Now showing 1 - 4 of 4
Publication Metadata only Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy(AMER ASSOC ADVANCEMENT SCIENCE, 2015) AYDINER, ELİF; Lo, Bernice; Zhang, Kejian; Lu, Wei; Zheng, Lixin; Zhang, Qian; Kanellopoulou, Chrysi; Zhang, Yu; Liu, Zhiduo; Fritz, Jill M.; Marsh, Rebecca; Husami, Ammar; Kissell, Diane; Nortman, Shannon; Chaturvedi, Vijaya; Haines, Hilary; Young, Lisa R.; Mo, Jun; Filipovich, Alexandra H.; Bleesing, Jack J.; Mustillo, Peter; Stephens, Michael; Rueda, Cesar M.; Chougnet, Claire A.; Hoebe, Kasper; McElwee, Joshua; Hughes, Jason D.; Karakoc-Aydiner, Elif; Matthews, Helen F.; Price, Susan; Su, Helen C.; Rao, V. Koneti; Lenardo, Michael J.; Jordan, Michael B.Mutations in the LRBA gene (encoding the lipopolysaccharide-responsive and beige-like anchor protein) cause a syndrome of autoimmunity, lymphoproliferation, and humoral immune deficiency. The biological role of LRBA in immunologic disease is unknown. We found that patients with LRBA deficiency manifested a dramatic and sustained improvement in response to abatacept, a CTLA4 (cytotoxic T lymphocyte antigen-4)-immunoglobulin fusion drug. Clinical responses and homology of LRBA to proteins controlling intracellular trafficking led us to hypothesize that it regulates CTLA4, a potent inhibitory immune receptor. We found that LRBA colocalized with CTLA4 in endosomal vesicles and that LRBA deficiency or knockdown increased CTLA4 turnover, which resulted in reduced levels of CTLA4 protein in FoxP3(+) regulatory and activated conventional Tcells. In LRBA-deficient cells, inhibition of lysosome degradation with chloroquine prevented CTLA4 loss. These findings elucidate a mechanism for CTLA4 trafficking and control of immune responses and suggest therapies for diseases involving the CTLA4 pathway.Publication Open Access Expanding the clinical and immunological phenotypes and natural history of MALT1 deficiency(2022-04-01) KOLUKISA, BURCU; BARIŞ, SAFA; ÖZEN, AHMET OĞUZHAN; AYDINER, ELİF; Sefer A. P., Abolhassani H., Ober F., KAYAOĞLU B., Eltan S. B., Kara A., ERMAN B., Yilmaz N. S., Aydogmus C., Aydemir S., et al.Purpose MALT1 deficiency is a combined immune deficiency characterized by recurrent infections, eczema, chronic diarrhea, and failure to thrive. Clinical and immunological characterizations of the disease have not been previously reported in large cohorts. We sought to determine the clinical, immunological, genetic features, and the natural history of MALT-1 deficiency. Methods The clinical findings and treatment outcomes were evaluated in nine new MALT1-deficient patients. Peripheral lymphocyte subset analyses, cytokine secretion, and proliferation assays were performed. We also analyzed ten previously reported patients to comprehensively evaluate genotype/phenotype correlation. Results The mean age of patients and disease onset were 33 +/- 17 and 1.6 +/- 0.7 months, respectively. The main clinical findings of the disease were recurrent infections (100%), skin involvement (100%), failure to thrive (100%), oral lesions (67%), chronic diarrhea (56%), and autoimmunity (44%). Eosinophilia and high IgE were observed in six (67%) and two (22%) patients, respectively. The majority of patients had normal T and NK cells, while eight (89%) exhibited reduced B cells. Immunoglobulin replacement and antibiotics prophylaxis were mostly ineffective in reducing the frequency of infections and other complications. One patient received hematopoietic stem cell transplantation (HSCT) and five patients died as a complication of life-threatening infections. Analyzing this cohort with reported patients revealed overall survival in 58% (11/19), which was higher in patients who underwent HSCT (P = 0.03). Conclusion This cohort provides the largest analysis for clinical and immunological features of MALT1 deficiency. HSCT should be offered as a curative therapeutic option for all patients at the early stage of life.Publication Metadata only Low Density Granulocytes and Dysregulated Neutrophils Driving Autoinflammatory Manifestations in NEMO Deficiency(SPRINGER/PLENUM PUBLISHERS, 2022) ÖZEN, AHMET OĞUZHAN; Yilmaz, Naz Surucu; Eltan, Sevgi Bilgic; Kayaoglu, Basak; Geckin, Busranur; Heredia, Raul Jimenez; Sefer, Asena Pinar; Kiykim, Ayca; Nain, Ercan; Kasap, Nurhan; Dogru, Omer; Yucelten, Ayse Deniz; Cinel, Leyla; Karasu, Gulsun; Yesilipek, Akif; Sozeri, Betul; Kaya, Goksu Gokberk; Yilmaz, Ismail Cem; Baydemir, Ilayda; Aydin, Yagmur; Kahraman, Deniz Cansen; Haimel, Matthias; Boztug, Kaan; Karakoc-Aydiner, Elif; Gursel, Ihsan; Ozen, Ahmet; Baris, Safa; Gursel, MaydaNF-kappa B essential modulator (NEMO, IKK-gamma) deficiency is a rare combined immunodeficiency caused by mutations in the IKBKG gene. Conventionally, patients are afflicted with life threatening recurrent microbial infections. Paradoxically, the spectrum of clinical manifestations includes severe inflammatory disorders. The mechanisms leading to autoinflammation in NEMO deficiency are currently unknown. Herein, we sought to investigate the underlying mechanisms of clinical autoinflammatory manifestations in a 12-years old male NEMO deficiency (EDA-ID, OMIM #300,291) patient by comparing the immune profile of the patient before and after hematopoietic stem cell transplantation (HSCT). Response to NF-kB activators were measured by cytokine ELISA. Neutrophil and low-density granulocyte (LDG) populations were analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMC) transcriptome before and after HSCT and transcriptome of sorted normal-density neutrophils and LDGs were determined using the NanoString nCounter gene expression panels. ISG15 expression and protein ISGylation was based on Immunoblotting. Consistent with the immune deficiency, PBMCs of the patient were unresponsive to toll-like and T cell receptor-activators. Paradoxically, LDGs comprised 35% of patient PBMCs and elevated expression of genes such as MMP9, LTF, and LCN2 in the granulocytic lineage, high levels of IP-10 in the patient's plasma, spontaneous ISG15 expression and protein ISGylation indicative of a spontaneous type I interferon (IFN) signature were observed, all of which normalized after HSCT. Collectively, our results suggest that type I IFN signature observed in the patient, dysregulated LDGs and spontaneously activated neutrophils, potentially contribute to tissue damage in NEMO deficiency.Publication Metadata only Expanding the Clinical and Immunological Phenotypes and Natural History of MALT1 Deficiency(SPRINGER/PLENUM PUBLISHERS, 2022) ÖZEN, AHMET OĞUZHAN; Sefer, Asena Pinar; Abolhassani, Hassan; Ober, Franziska; Kayaoglu, Basak; Eltan, Sevgi Bilgic; Kara, Altan; Erman, Baran; Yilmaz, Naz Surucu; Aydogmus, Cigdem; Aydemir, Sezin; Charbonnier, Louis-Marie; Kolukisa, Burcu; Azizi, Gholamreza; Delavari, Samaneh; Momen, Tooba; Aliyeva, Simuzar; Demirkol, Yasemin Kendir; Tekin, Saban; Kiykim, Ayca; Baser, Omer Faruk; Cokugras, Haluk; Gursel, Mayda; Karakoc-Aydiner, Elif; Ozen, Ahmet; Krappmann, Daniel; Chatila, Talal A.; Rezaei, Nima; Baris, SafaPurpose MALT1 deficiency is a combined immune deficiency characterized by recurrent infections, eczema, chronic diarrhea, and failure to thrive. Clinical and immunological characterizations of the disease have not been previously reported in large cohorts. We sought to determine the clinical, immunological, genetic features, and the natural history of MALT-1 deficiency. Methods The clinical findings and treatment outcomes were evaluated in nine new MALT1-deficient patients. Peripheral lymphocyte subset analyses, cytokine secretion, and proliferation assays were performed. We also analyzed ten previously reported patients to comprehensively evaluate genotype/phenotype correlation. Results The mean age of patients and disease onset were 33 +/- 17 and 1.6 +/- 0.7 months, respectively. The main clinical findings of the disease were recurrent infections (100%), skin involvement (100%), failure to thrive (100%), oral lesions (67%), chronic diarrhea (56%), and autoimmunity (44%). Eosinophilia and high IgE were observed in six (67%) and two (22%) patients, respectively. The majority of patients had normal T and NK cells, while eight (89%) exhibited reduced B cells. Immunoglobulin replacement and antibiotics prophylaxis were mostly ineffective in reducing the frequency of infections and other complications. One patient received hematopoietic stem cell transplantation (HSCT) and five patients died as a complication of life-threatening infections. Analyzing this cohort with reported patients revealed overall survival in 58% (11/19), which was higher in patients who underwent HSCT (P = 0.03). Conclusion This cohort provides the largest analysis for clinical and immunological features of MALT1 deficiency. HSCT should be offered as a curative therapeutic option for all patients at the early stage of life.