Omer Karadag
Hacettepe University
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Featured researches published by Omer Karadag.
The New England Journal of Medicine | 2014
Qing Zhou; Dan Yang; Amanda K. Ombrello; Andrey Zavialov; Camilo Toro; Anton V. Zavialov; Deborah L. Stone; Jae Jin Chae; Sergio D. Rosenzweig; Kevin Bishop; Karyl S. Barron; Hye Sun Kuehn; Patrycja Hoffmann; Alejandra Negro; Wanxia L. Tsai; Edward W. Cowen; Wuhong Pei; Joshua D. Milner; Christopher Silvin; Theo Heller; David T. Chin; Nicholas J. Patronas; John S. Barber; Chyi-Chia R. Lee; Geryl Wood; Alexander Ling; Susan J. Kelly; David E. Kleiner; James C. Mullikin; Nancy J. Ganson
BACKGROUND We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, and systemic vasculopathy in three unrelated patients. We suspected a genetic cause because the disorder presented in early childhood. METHODS We performed whole-exome sequencing in the initial three patients and their unaffected parents and candidate-gene sequencing in three patients with a similar phenotype, as well as two young siblings with polyarteritis nodosa and one patient with small-vessel vasculitis. Enzyme assays, immunoblotting, immunohistochemical testing, flow cytometry, and cytokine profiling were performed on samples from the patients. To study protein function, we used morpholino-mediated knockdowns in zebrafish and short hairpin RNA knockdowns in U937 cells cultured with human dermal endothelial cells. RESULTS All nine patients carried recessively inherited mutations in CECR1 (cat eye syndrome chromosome region, candidate 1), encoding adenosine deaminase 2 (ADA2), that were predicted to be deleterious; these mutations were rare or absent in healthy controls. Six patients were compound heterozygous for eight CECR1 mutations, whereas the three patients with polyarteritis nodosa or small-vessel vasculitis were homozygous for the p.Gly47Arg mutation. Patients had a marked reduction in the levels of ADA2 and ADA2-specific enzyme activity in the blood. Skin, liver, and brain biopsies revealed vasculopathic changes characterized by compromised endothelial integrity, endothelial cellular activation, and inflammation. Knockdown of a zebrafish ADA2 homologue caused intracranial hemorrhages and neutropenia - phenotypes that were prevented by coinjection with nonmutated (but not with mutated) human CECR1. Monocytes from patients induced damage in cocultured endothelial-cell layers. CONCLUSIONS Loss-of-function mutations in CECR1 were associated with a spectrum of vascular and inflammatory phenotypes, ranging from early-onset recurrent stroke to systemic vasculopathy or vasculitis. (Funded by the National Institutes of Health Intramural Research Programs and others.).
Joint Bone Spine | 2008
Bunyamin Kisacik; Abdurrahman Tufan; Umut Kalyoncu; Omer Karadag; Ali Akdogan; Oztürk Ma; Sedat Kiraz; I. Ertenli; Meral Calguneri
AIMS The aim of this retrospective study was to investigate the correlation between MPV and the clinical disease activity indices of rheumatoid arthritis and ankylosing spondylitis. METHODS The study consisted of 32 active RA patients (males/females: 7/25, mean age: 49+/-13) and 30 active AS patients (males/females: 15/15, mean age: 36+/-12) along with 26 osteoarthritis (OA) patients (males/females: 4/22, mean age: 52+/-8) and 29 age-matched healthy subjects (males/females: 5/24, mean age: 41+/-7) as control groups for RA and AS, respectively. RESULTS MPV was significantly lower in both AS patients and RA patients with active disease as compared to controls (RA vs OA p<0.001, AS vs healthy subjects p<0.001). After treatment MPV values significantly increased in AS and RA (p<0.001 for all). However, MPV values remained somewhat lower in RA patients than OA patients (p=0.019). There was a negative correlation between MPV values and BASDAI scores in AS patients after two months of treatment (r=-0.507; p=0.004). CONCLUSION Our results suggest that assessment of MPV may provide additional information about inflammation in AS and RA.
American Journal of Human Genetics | 2013
Güher Saruhan-Direskeneli; Travis Hughes; Kenan Aksu; Gokhan Keser; Patrick Coit; Sibel Zehra Aydin; Fatma Alibaz-Oner; Sevil Kamali; Murat Inanc; Simon Carette; Gary S. Hoffman; Servet Akar; Fatos Onen; Nurullah Akkoc; Nader Khalidi; Curry L. Koening; Omer Karadag; Sedat Kiraz; Carol A. Langford; Carol A. McAlear; Zeynep Ozbalkan; Aşkın Ateş; Yasar Karaaslan; Kathleen Maksimowicz-McKinnon; Paul A. Monach; Huseyin T. E. Ozer; Emire Seyahi; Izzet Fresko; Ayse Cefle; Philip Seo
Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ~200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r(2) < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10(-9); and rs189754752, OR = 2.47, p = 4.22 × 10(-9)). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10(-12)). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10(-8)).
Annals of the Rheumatic Diseases | 2009
Emilio Filippucci; S Zehra Aydin; Omer Karadag; Fausto Salaffi; Marwin Gutierrez; Walter Grassi
Objective: The present study was mainly aimed at investigating the interobserver and intraobserver reproducibility of ultrasound (US) results in the assessment of Achilles tendon enthesopathy in patients with seronegative spondyloarthropathies (SpA). Methods: A total of 28 patients with a diagnosis of SpA according to the European Spondyloarthropathy Study Group criteria were included. The patient female/male ratio was 1.8 (18/10), mean age was 42 (range 25–75) years and mean disease duration was 9 (range 1–35) years. Mean (SD) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) scores were 32.4 (14.5) and 26.3 (9.2), respectively. Bilateral Achilles tendon US examinations were carried out independently by three investigators using a MyLab70 XVG (Esaote Biomedica, Genoa, Italy), equipped with a broadband 6–18 MHz linear probe. Each Achilles tendon was scanned for assessing the presence/absence of US findings indicative of enthesopathy according to the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) preliminary definition. The same findings were also scored on a 3-grade semiquantitative scoring system on which investigators reached a consensus prior to the study. Total additive scores per Achilles tendon were calculated. Results: Moderate to excellent interobserver and intraobserver agreements were found for most of the US findings indicative of enthesopathy. Similar results were obtained using semiquantitative assessments, with weighted κ values estimating the interobserver and intraobserver agreements for soft tissue inflammation of 0.696 and 0.816, respectively and for tissue damage 0.711 and 0.901, respectively. Conclusion: US assessment of Achilles tendon enthesopathy in patients with SpA, using the OMERACT preliminary definition, was found to be reliable. Bone irregularity and entheseal hypoechogenicity were the most difficult abnormalities to reach agreement on.
Echocardiography-a Journal of Cardiovascular Ultrasound and Allied Techniques | 2007
Alper Kepez; Ali Akdogan; L. Elif Sade; Ali Deniz; Umut Kalyoncu; Omer Karadag; Mutlu Hayran; Kudret Aytemir; I. Ertenli; Sedat Kiraz; Meral Calguneri; Giray Kabakci; Lale Tokgozoglu
Background: Cardiac involvement is one of the major problems in systemic sclerosis (SSc). Subclinical cardiac involvement has a higher frequency than thought previously. In this study we investigated whether subclinical cardiac involvement can be detected by using echocardiographic strain imaging in SSc patients without pulmonary hypertension. Methods: Echocardiographic examinations were performed to 27 SSc patients and 26 healthy controls. Left ventricular strain parameters were obtained from apical views and average strain value was calculated from these measurements. Results: There were no significant differences between patients and controls regarding two‐dimensional (2D), conventional Doppler and tissue Doppler velocity measurements. Strain was reduced in 6 of 12 segments of the left ventricle (LV) and in 1 of 2 segments of the right ventricle (RV). Strain rate (SR) was reduced in 2 of 12 segments of the LV and 1 of 2 segments of the RV in SSc patients as compared to controls (P < 0.05 for all). These involvements did not match any particular coronary artery distribution. More important differences were detected by average strain and SR values of the LV between patients and controls (19.78 ± 3.00% vs 23.41 ± 2.73%, P < 0.001; 2.01 ± 0.41 vs 2.23 ± 0.27/sec, P = 0.026, respectively). Furthermore, carbon monoxide diffusion capacity (DLCO) in scleroderma patients significantly correlated with LV average strain (r = 0.59; P = 0.001). Conclusion: Evaluation of ventricular function by using echocardiographic strain imaging appears to be useful to detect subclinical cardiac involvement in SSc patients with normal standard echocardiographic and tissue Doppler velocity findings.
Scandinavian Journal of Infectious Diseases | 2007
Umut Kalyoncu; Omer Karadag; Ali Akdogan; Bunyamin Kisacik; Mustafa Erman; Sibel Ergüven; A. Ihsan Ertenli
Patients with rheumatoid arthritis (RA) have an increased risk of infection as a result of alterations in immune regulation, debility, and comorbid illnesses. TNF-α is of central importance in the pathophysiological responses to infection and inflammation, and plays a crucial role in host defence. Pneumocystis carinii is an opportunistic pathogen that commonly affects individuals with inadequate T-cell mediated immune response. Patients with acquired immune deficiency, as well as those receiving immunosuppressive drugs for various conditions have an increased risk of P. carinii pneumonia (PCP). We report the development of PCP in a woman with RA shortly after the initiation of anti-TNF-α treatment with adalimumab.
Arthritis Research & Therapy | 2012
Ziver Sahin; Muge Bicakcigil; Kenan Aksu; Sevil Kamali; Servet Akar; Fatos Onen; Omer Karadag; Zeynep Ozbalkan; Aşkın Ateş; Huseyin T. E. Ozer; Vuslat Yilmaz; Emire Seyahi; Mehmet Akif Öztürk; Ayse Cefle; Veli Cobankara; A. Mesut Onat; Ercan Tunc; Nurşen Düzgün; Sibel Zehra Aydin; Neslihan Yilmaz; Izzet Fresko; Yasar Karaaslan; Sedat Kiraz; Nurullah Akkoc; Murat Inanc; Gokhan Keser; F. Aytül Uyar; Güher Saruhan-Direskeneli
IntroductionHLA-B*51 and HLA-B*52 are two close human leukocyte antigen (HLA) allele groups with minor amino acid differences. However, they are associated with two different vasculitides (HLA-B*51 in Behçets disease and HLA-B*52 in Takayasus arteritis (TAK)) and with major clinical and immunological differences. In this study, we aimed to screen a large cohort of TAK patients from Turkey for the presence of HLA-B*51 and HLA-B*52 as susceptibility and severity factors.MethodsTAK patients (n = 330) followed at a total of 15 centers were included in the study. The mean age of the patients was 37.8 years, and 86% were women. DNA samples from the patients and healthy controls (HC; n = 210) were isolated, and the presence of HLA-B*51 or HLA-B*52 was screened for by using PCR with sequence-specific primers.ResultsWe found a significant association of HLA-B*52 with TAK (20.9% vs HC = 6.7%, P = 0.000, OR = 3.7, 95% CI = 2.02 to 6.77). The distribution of HLA-B*51 did not differ between TAK patients and HCs (22.7% vs 24.8%, OR = 0.9, 95% CI = 0.60 to 1.34). The presence of HLA-B*52 decreased in late-onset patients (> 40 years of age; 12.0%, P = 0.024, OR = 0.43, 95% CI = 0.20 to 0.91). Patients with angiographic type I disease with limited aortic involvement also had a lower presence of HLA-B*52 compared to those with all other disease subtypes (13.1% vs 26%, P = 0.005, OR = 0.43, 95% CI = 0.23 to 0.78).ConclusionsIn this study, the previously reported association of TAK with HLA-B*52 in other populations was confirmed in patients from Turkey. The functional relevance of HLA-B*52 in TAK pathogenesis needs to be explored further.
The Journal of Rheumatology | 2015
Ezgi Deniz Batu; Omer Karadag; Ekim Z. Taskiran; Umut Kalyoncu; Ivona Aksentijevich; Mehmet Alikasifoglu; Seza Ozen
To the Editor: Deficiency of adenosine deaminase 2 (DADA2) causes a vasculopathy with autoinflammatory features associated with mutations in CECR1 1. The phenotype of DADA2 varies from only cutaneous lesions to full-blown systemic disease with central nervous system (CNS) involvement and aneurysms in visceral arteries that may overlap with the spectrum of polyarteritis nodosa (PAN)1,2,3. The Chapel Hill Consensus Conference (CHCC) 2012 defines PAN as a necrotizing vasculitis of medium or small arteries without glomerulonephritis or vasculitis in arterioles, venules, or capillaries and not associated with antineutrophil cytoplasmic antibodies4. Now, with the discovery of DADA2, we know that monogenic disorders may cause a PAN-like vasculopathy. Thus, DADA2 should be classified under the group of “vasculitis with a probable cause” in CHCC 20124. We herein present the characteristics of 6 DADA2 patients and their response to various therapies. Three of our patients had been initially screened at the U.S. National Institutes of Health (NIH) because they had suggestive features for the CECR1 mutations. Subsequently, we screened 17 patients with suggestive features and identified 3 new cases. We have evaluated the course of these patients for a followup of median 8.5 years. All patients were Turkish and were followed in the departments of Rheumatology and Pediatric Rheumatology at Hacettepe University, Ankara, Turkey. Three (patients 2, 3, and 5) had been included in a previous paper2. Peripheral blood samples for DNA extraction were obtained. Sanger sequencing was performed to sequence 10 exons of CECR1 in NIH (n = 3) and Hacettepe University (n = 3). Primer sequences are available in the Appendix. PCR products were directly sequenced using ABI Prism 3130 Automated Sequencer (Applied Biosystems). We defined 6 DADA2 patients from 5 families. The characteristics and treatment of patients … Address correspondence to Dr. S. Ozen, Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey. E-mail: sezaozen{at}hacettepe.edu.tr
Arthritis & Rheumatism | 2015
Paul Renauer; Güher Saruhan-Direskeneli; Patrick Coit; Adam Adler; Kenan Aksu; Gokhan Keser; Fatma Alibaz-Oner; Sibel Zehra Aydin; Sevil Kamali; Murat Inanc; Simon Carette; David Cuthbertson; Gary S. Hoffman; Servet Akar; Fatos Onen; Nurullah Akkoc; Nader Khalidi; Curry L. Koening; Omer Karadag; Sedat Kiraz; Carol A. Langford; Kathleen Maksimowicz-McKinnon; Carol A. McAlear; Zeynep Ozbalkan; Aşkın Ateş; Yasar Karaaslan; Nurşen Düzgün; Paul A. Monach; Huseyin T. E. Ozer; Eren Erken
Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome‐wide association analysis of Takayasu arteritis.
Rheumatology International | 2009
Asli Kurne; Rana Karabudak; Omer Karadag; Gul Yalcin-Cakmakli; Kader Karlı-Oğuz; Kivilcim Yavuz; Meral Calguneri; Mehmet Akif Topcuoglu
Severe primary central nervous system (CNS) involvement such as vasculitis and pachymeningitis can rarely occur in rheumatoid arthritis (RA) even in the absence of systemic disease activation. The authors illustrate a female patient with well-controlled RA who presented with headaches, encephalopathy, seizures and relapsing focal neurological deficits. Primary rheumatoid cerebral vasculitis and pachymeningitis were diagnosed based on suggestive brain magnetic resonance (MR) imaging, MR angiography, cerebrospinal fluid analysis and cerebral angiography. MR showed abnormal leptomeningeal enhancement and hyperintense FLAIR signal in the cortical subarachnoid spaces consistent with pachymeningitis. Cerebral angiography findings were consistent with vasculitis. Aggressive treatment resulted in significant clinicoradiological resolution. Cerebral vasculitis is a rare but certain manifestation of RA. This complication can be diagnosed in the presence of suggestive angiographic and CSF findings. The condition may be steroid resistant, and needs to be treated more aggressively.