Research Project: Otoimmün Nörolojik Hastalıklarda İmmünopatogenezin ve Klinik Özelliklerle İlişkili Immünolojik Parametrelerin Araştırılması
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Contributors
Funders
ID
TB.00387
Authors
Vural, Atay
Faculty Member
Publications
Pediatric-onset chronic inflammatory demyelinating polyneuropathy: a multicenter study
(Elsevier Science Inc, 2023) Kızılırmak, Ali Burak; Vural, Atay; Yousefi, Mohammadreza; Uzan, Gamze Sarikaya; Yuksel, Deniz; Aksoy, Erhan; Oztoprak, Ulkuhan; Canpolat, Mehmet; Ozturk, Selcan; Yildirim, Celebi; Gulec, Ayten; Per, Huseyin; Gumus, Hakan; Okuyaz, Cetin; Direk, Meltem Cobanoullari; Kosmur, Mustafa; Unalp, Aycan; Yilmaz, Unsal; Bektas, Omer; Teber, Serap; Aliyeva, Nargiz; Dundar, Nihal Olgac; Gencpinar, Pinar; Gurkas, Esra; Yilmaz, Sanem Keskin; Kanmaz, Seda; Tekgtil, Hasan; Aksoy, Ayse; Tuncer, Gokcen Oz; Arslan, Elif Acar; Tosun, Ayse; Ayanoglu, Muge; Bodur, Muhittin; Unay, Bulent; Kurul, Semra Hiz; Yis, Uluc; KUTTAM (Koç University Research Center for Translational Medicine); School of Medicine; Yes; Research Center; SCHOOL OF MEDICINE
Background: To evaluate the clinical features, demographic features, and treatment modalities of pediatric-onset chronic inflammatory demyelinating polyneuropathy (CIDP) in Turkey. Methods: The clinical data of patients between January 2010 and December 2021 were reviewed retrospectively. The patients were evaluated according to the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society Guideline on the management of CIDP (2021). In addition, patients with typical CIDP were divided into two groups according to the first-line treatment modalities (group 1: IVIg only, group 2: IVIg + steroid). The patients were further divided into two separate groups based on their magnetic resonance imaging (MRI) characteristics. Results: A total of 43 patients, 22 (51.2%) males and 21 (48.8%) females, were included in the study. There was a significant difference between pretreatment and post-treatment modified Rankin scale (mRS) scores (P < 0.05) of all patients. First-line treatments include intravenous immunoglobulin (IVIg) (n = 19, 4 4.2%), IVIg + steroids (n = 20, 46.5%), steroids (n = 1, 2.3%), IVIg + steroids + plasmapheresis (n = 1, 2.3%), and IVIg + plasmapheresis (n = 1, 2.3%). Alternative agent therapy consisted of azathioprine (n = 5), rituximab (n = 1), and azathioprine + mycophenolate mofetil + methotrexate (n = 1). There was no difference between the pretreatment and post-treatment mRS scores of groups 1 and 2 (P > 0.05); however, a significant decrease was found in the mRS scores of both groups with treatment (P < 0.05). The patients with abnormal MRI had significantly higher pretreatment mRS scores compared with the group with normal MRI (P < 0.05). Conclusions: This multicenter study demonstrated that first-line immunotherapy modalities (IVIg vs IVIg + steroids) had equal efficacy for the treatment of patients with CIDP. We also determined that MRI features might be associated with profound clinical features, but did not affect treatment response.
CD20+ natural killer cells are polyfunctional, memory-like cells that are enriched in inflammatory disorders
(Oxford Univ Press, 2025) Albayrak, Özgür; Tiryaki, Ergün; Kızılırmak, Ali Burak; Doran, Tansu; Gökmenoğlu, Gökçe; Yüksel, Muhammed; Ulukan, Bürge; Arıkan, Çiğdem; Vural, Seçil; Zeybel, Müjdat; Vural, Atay; Akkaya, Nazan; Ulukan, Bürge; Tiryaki, Ergün; Akkaya, Nazan; Doran, Tansu; Kızılırmak, Ali Burak; Uzulmez, Mina; Baytekin, Isil; Soylu, Onder Kemal; Esendagli, Gunes; Meinl, Ingrid; Koseoglu, Mesrure; Yuksel, Burcu; Erus, Suat; Soysal, Aysun; Meinl, Edgar; KUTTAM (Koç University Research Center for Translational Medicine); Graduate School of Health Sciences; School of Medicine; Yes; Gökmenoğlu, Gökçe; SCHOOL OF MEDICINE; GRADUATE SCHOOL OF HEALTH SCIENCES; Research Center
While CD20 was initially characterized as a B cell-specific marker, its expression on memory T cells has expanded our understanding of this molecule's distribution and function. Here, we identify a previously unrecognized CD20-expressing NK cell population and demonstrate its functional significance. CD56(+)CD20(+) NK cells exhibit hallmarks of cellular activation, including elevated NKp46, CD69, and CD137 expression, enhanced proliferative capacity, and increased production of inflammatory cytokines (IFN-gamma, GM-CSF, TNF-alpha, IL-10). Functional analyses revealed enhanced cytotoxicity against K562 targets, correlating with increased expression of cytolytic mediators including granzymes A, B, and K, perforin, FASL, and TRAIL. Single-cell transcriptional profiling demonstrated that MS4A1-expressing NK cells possess a distinct molecular signature characterized by elevated granzyme K expression and memory-like features. These cells preferentially localize to secondary lymphoid organs and accumulate in inflammatory tissues. Notably, CD56(+)CD20(+) NK cells are enriched in multiple inflammatory conditions, including multiple sclerosis, autoimmune hepatitis, hepatitis B infection, hepatocellular carcinoma, and lung cancer. Treatment with rituximab depletes this population, suggesting potential therapeutic implications. Our findings establish CD20(+) NK cells as a functionally distinct lymphocyte subset with enhanced effector capabilities and tissue-homing properties, providing new insights into immune regulation in inflammatory diseases.
Myelin oligodendrocyte glycoprotein antibody associated central nervous system demyelinating disease: a tertiary center experience from Turkey
(Elsevier, 2020) Vural, Atay; İnan, Berin; Göçmen, Rahşan; Çolpak, Ayşe İlksen; Meinl, Edgar; Karabudak, Rana; Tuncer, Aslı; School of Medicine; KUTTAM (Koç University Research Center for Translational Medicine); Yes; SCHOOL OF MEDICINE; Research Center
Background: To identify the clinical and radiological characteristics of adult patients with myelin oligodendrocyte glycoprotein antibody disease (MOG-AD) in a Turkish cohort. Methods: Clinical and radiological data were obtained retrospectively. Serological testing was done with fixed and live cell-based assays. Results: Optic neuritis was the most common presenting symptom, and neuromyelitis optica spectrum disorder (NMOSD) without aquaporin-4 antibody (AQP4-IgG) was the most common phenotype. Most patients had a relapsing course. Steroid dependency was common. Conus involvement was a frequent clinical and radiological feature. Radiological features such as long segment involvement and perineural optic nerve gadolinium enhancement were also typical in our cohort. One patient presented with encephalopathy and seizures, pointing out to the importance of testing of myelin oligodendrocyte antibody (MOG-IgG) in such patients as well. Conclusion: Myelin oligodendrocyte glycoprotein antibody disease is a heterogeneous clinical entity with characteristic clinical and radiological features. Our single-center experience underlines prominent clinical and magnetic resonance imaging (MRI) features and provides our treatment experiences.
Myelin oligodendrocyte glycoprotein antibodies in genetic leukodystrophies
(Elsevier B.V., 2022) Doran, Tansu; Vural, Atay; Yousefi, Mohammadreza; Eroğlu Ertuğrul, Nesibe Gevher; Pekgüzel, Faruk; Guenbey, Ceren; Topçu, Meral; Oğuz, Kader K.; Özkara, Hatice Asuman; Anlar, Banu; KUTTAM (Koç University Research Center for Translational Medicine); School of Medicine; Yes; Research Center; SCHOOL OF MEDICINE
Accumulation of intermediate metabolites due to enzyme deficiencies and demyelination can provoke inflammation in genetic leukodystrophies. Thirty patients with genetic leukodystrophy and 48 healthy control sera were tested for anti-myelin oligodendrocyte glycoprotein (MOG) antibodies by fixed and/or live cell-based assays. MOG-IgG was detected in two late infantile metachromatic leukodystrophy (MLD) cases, both of which were also weakly positive for IgG1, and one with IgG3 as the dominant anti-MOG IgG subclass. MOG-IgG was borderline positive in a vanishing white matter (VWM) disease patient. These results suggest that inherited metabolic or degenerative processes can have an autoimmune component, possibly as an epiphenomenon.
Frequency of myelin oligodendrocyte glycoprotein antibodies in pediatric onset multiple sclerosis
(Elsevier, 2022) Doran, Tansu; Vural, Atay; Yousefi, Mohammadreza; Solmaz, İsmail; Konuşkan, Bahadır; Öncel, İbrahim; Anlar, Banu; KUH (Koç University Hospital); School of Medicine; Yes; KUH (KOÇ UNIVERSITY HOSPITAL); SCHOOL OF MEDICINE
Background: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are associated with acute demyelinating syndromes and only rarely detected in multiple sclerosis (MS). As MOG-Ab associated disease is common in childhood, we speculated young patients might be more likely to produce MOG-Ab and investigated the frequency of MOG-Ab seropositivity in pediatric onset MS (POMS).Material and methods: Patients who experienced their first acute demyelinating event before age 18 years and were diagnosed with MS during follow-up were included in this single-center study. Patient data were retrieved from clinical records. Serum samples obtained and frozen at clinical visits were analyzed for MOG-Ab by a live cell-based assay (CBA) measuring delta mean fluorescence intensity (MFI) and MFI ratio. The control group consisted of patients referred to pediatric neurology for headache or vertigo and who had no neurological dis-order (n = 48). Another control group consisted of patients with systemic inflammatory disorders systemic lupus erythematosus (n = 17) and juvenile idiopathic arthritis (n = 13) diagnosed in the rheumatology clinic.Results: The patient group (n 1/4 122, F/M: 90/32, mean age 17.8 & PLUSMN; 2.6 years) were initially diagnosed as: MS, 62/122 (50.8%), clinically isolated syndrome, 43/122 (35.2%), radiologically isolated syndrome, 9/122 (7.3%), and acute disseminated encephalomyelitis 8/122 (6.5%). All received the final diagnosis of POMS. Serum was sampled 22.4 & PLUSMN; 29.2 (0-132) months after the first episode. None of the control groups had MOG-Ab positivity while 2/122 (1.6%) POMS cases had MOG-Abs, and a third patient had positive MFI and a MFI ratio slightly below the cut-off. These three patients' initial and final diagnoses were MS, their annualized relapsing rates (ARRs) were 0.4-0.6, and most recent Expanded Disability Status Scale was 0.Conclusion: Low titers of MOG-Ab can be detected in a small number of POMS patients at similar frequency with adult MS. Our POMS cases with MOG-Abs presented brainstem-cerebellar findings or seizures and had low ARR. Further series and longer follow-up will define whether these cases differ significantly from MOG-Ab negative POMS cases.
