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Benign MS Hastalarinin B Hücre İmmünfenotiplemesi ve B Hücresine Özgü Moleküllerin Ekspresyon Analizi

Year 2019, Volume: 9 Issue: 3, 105 - 112, 01.12.2019

Abstract

DOI: 10.26650/experimed.2019.19026

Amaç: Multipl Skleroz (MS), aksonal dejenerasyona, demiyelinizasyona ve inflamasyona bağlı gelişen, merkezi sinir sistemini etkileyen progresif bir hastalıktır. Bu çalışmada benign MS (BMS) grubunda periferik kan B hücre immünofenotiplerinin ve B hücresi ile ilişkili gen ekspresyonlarının hastalık ve bilişsel süreçlerle ilişkisinin araştırılması hedeflenmiştir.

Gereç ve Yöntem: Yirmi BMS hastası, 16 benign olmayan MS (Non-BMS) hastası ve 28 sağlıklı gönüllü çalışmaya dahil edildi. Daha önce periferik kan hücrelerinde yapılan gen mikroarray çalışması ile gruplar arasında ekspresyonu değişikliği gözlenen genlerin validasyonu gerçek zamanlı PZR ile yapıldı. Periferik B hücrelerinin immünofenotiplemesi akım sitometrisi ile değerlendirildi. Bilişsel fonksiyonlar ile gen ekspresyon seviyeleri ve B hücre alttipleri arasındaki olası ilişki araştırıldı.

Bulgular: Naif (CD19+ IgD+CD27-) B hücrelerinin BMS grubunda sağlıklılara göre yüksek olduğu, hafıza B hücrelerinin zıt yönde değişiklik gösterdiği gözlendi. Dönüşmemiş hafıza B hücrelerinin (CD19+IgD+CD27+) ise benign grupta sağlıklılara göre yüksek olduğu belirlendi. BANK ve BLNK gen ekspresyonları her iki MS grubunda da sağlıklılardan düşük olarak belirlendi. Nöropsikolojik incelemeler ve kognitif testler sonucunda, BMS’te motor süreçlerin Non-BMS’ye göre korunduğu gözlendi.

Sonuç: Bu bulgular B hücresi işlevlerinin moleküler ve hücresel etkileri olabileceği ve inflamasyon ile klinik progresyonda gerilemeye yol açabileceği yönündeki görüşleri desteklemektedir. Değişiklik gösteren moleküllerin MS hastalığında prognostik biyobelirteç olarak rol oynaması da mümkündür.

Cite this article as: Şen M, Akbayır E, Türkoğlu R, Tüzün E, Yılmaz V. B Cell Immunophenotyping and Expression Analysis of B Cell Specific Molecules of Patients with Benign Multiple Sclerosis. Experimed 2019; 9(3): 105-12.

References

  • 1. Garg N, Smith TW. An update on immunopathogenesis, diagnosis and treatment of multiple sclerosis. Brain Behav 2015; 5: 1-13. [CrossRef] 2. Samkoff LM, Goodman AD. Multiple Sclerosis and CNS İnflammatory Disorders,Wiley-Blackwell; 2014. [CrossRef] 3. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: Results of an international survey. Neurology 1996; 46: 907-11. [CrossRef] 4. Hawkins SA, McDonell GV. Benign multiple sclerosis? Clinical course, long term follow up, and assessment of prognostic factors. J Neurol Neurosurg Psychiatry 1999; 67: 148-52. [CrossRef] 5. Ozakbas S, Turkoglu R, Tamam Y, Terzi M, Taskapilioglu O, Yucesan C, et al N. Prevalence of and risk factors for cognitive impairment in patients with relapsing-remitting multiple sclerosis: Multi-center, controlled trial. Mult Scler Relat Disord 2018; 22: 70-6. [CrossRef] 6. Tuzun E. Multipl skleroz patogenezinde B hücrelerinin rolü ve B hücre karşıtı monoklonal antikor tedavileri. Nöropsikiyatri Arşivi 2011; 48: 73-8. [CrossRef] 7. Sospedra M, Martin R. Immunology of multiple sclerosis. Annu Rev Immunol 2005; 23: 683-747. [CrossRef] 8. Naegelin Y, Naegelin P, von Felten S, Lorscheider J, Sonder J, Uitdehaag BMJ, et al. Association of Rituximab Treatment With Disability Progression Among Patients With Secondary Progressive Multiple Sclerosis JAMA Neurol 2019; 76: 274-81. [CrossRef] 9. Yamout BI, El-Ayoubi NK, Nicolas J, El Kouzi Y, Khoury SJ, Zeineddine MM.Safety and Efficacy of Rituximab in Multiple Sclerosis: A Retrospective Observational Study. J Immunol Res 2018; 2018: doi: 10.1155/2018/9084759. [CrossRef] 10. Achiron A, Feldman A, Magalashvili D, Dolev M, Gurevich M. Suppressed RNA-polymerase 1 pathway is associated with benign multiple sclerosis. PLoS One 2012; 7: doi: 10.1371/journal.pone.0046871. [CrossRef] 11. Yang J, Ren J, Yang Y, Sun J, Zhou X, Zheng S, et al. BANK1 alters B cell responses and influences the interactions between B cells and induced T regulatory cells in mice with collagen-induced arthritis. Arthritis Res Ther 2018; 20: 9. doi: 10.1186/s13075-017-1503-x. [CrossRef] 12. Kurtzke, J.F., A reassessment of the distribution of multiple sclerosis. Acta Neurologica Scandinavica 1975; 51: 110-36. [CrossRef] 13. Willer CJ, Dyment DA, Sadovnick AD, Ebers GC. Maternal-offspring HLA-DRB1 compatibility in multiple sclerosis. Tissue Antigens 2005; 66: 44-7. [CrossRef] 14. Düzgün N. İmmün Sistemin Tanıtımı. s: 97-122. Available from: URL: http://ichastaliklariromatoloji.medicine.ankara.edu.tr/files/2014/02/%C4%B0mm%C3%BCn-Sistemin-Tan%C4%B1t%C4%B1m%C4%B1.pdf 15. O’Connor BP, Raman VS, Erickson LD, Cook WJ, Weaver LK, Ahonen C, et al. BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med 2004; 199: 91-8. [CrossRef] 16. Aktura ŞD, Yılmaz V, Özkan-Yaşargün D, Ulusoy C, Tüzün E, Türkoğlu R. Peripheral blood memory B cell frequency predicts conversion from clinically isolated syndrome to multiple sclerosis. Mult Scler Relat Disord 2018; 23: 9-14. [CrossRef] 17. Komai T, Inoue M, Okamura T, Morita K, Iwasaki Y, Sumitomo S, et al. Transforming growth factor-β and interleukin-10 synergistically regulate humoral immunity via modulating metabolic signals. Front Immunol 2018; 9: 1364. doi: 10.3389/fimmu.2018.01364. [CrossRef] 18. Molnarfi N, Bjarnadóttir K, Benkhoucha M, Juillard C, Lalive PH. Activation of human B cells negatively regulates TGF-β1 production. J Neuroinflammation 2017; 14: 13. doi: 10.1186/s12974-017-0798-5. [CrossRef]

B Cell Immunophenotyping and Expression Analysis of B Cell Specific Molecules of Patients with Benign Multiple Sclerosis

Year 2019, Volume: 9 Issue: 3, 105 - 112, 01.12.2019

Abstract

DOI: 10.26650/experimed.2019.19026

Objective: Multiple Sclerosis (MS) is a progresive and an immune mediated inflammatory central nervous disease. The focus of this study was to determine the possible relationship between B cell immunophenotypes and related gene expressions in the benign MS (BMS) group with disease and cognitive processes.

Material and Method: Twenty BMS patients, 16 non-BMS and 28 healthy volunteers were included in the study. Gene expression was performed by real-time PCR (RT-PCR). Immunophenotyping of peripheral B cells was also evaluated by flow cytometry. The relationship between cognitive functions and gene expression levels and B cell subtypes was investigated.

Results: It was observed that naïve (CD19+ IgD+CD27-) cells were higher in the BMS group compared to the healthy group (HC), and memory B cells showed opposite changes. Un-switched memory B cells(CD19+IgD+CD27+) were found to be higher in the benign group than in the HC. The expression of BANK and BLNK was found to be lower in both MS groups than in the HC. As a result of neuropsychological examinations and cognitive tests; it was observed that motor processes in BMS were better protected than Non-BMS.

Conclusion: These findings support that B cell functions may have molecular and cellular effects, and may lead to regression in inflammation and clinical progression. Molecules showing significant changes in our study may play a role as prognostic biomarkers in MS.

Cite this article as: Şen M, Akbayır E, Türkoğlu R, Tüzün E, Yılmaz V. B Cell Immunophenotyping and Expression Analysis of B Cell Specific Molecules of Patients with Benign Multiple Sclerosis. Experimed 2019; 9(3): 105-12.

References

  • 1. Garg N, Smith TW. An update on immunopathogenesis, diagnosis and treatment of multiple sclerosis. Brain Behav 2015; 5: 1-13. [CrossRef] 2. Samkoff LM, Goodman AD. Multiple Sclerosis and CNS İnflammatory Disorders,Wiley-Blackwell; 2014. [CrossRef] 3. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: Results of an international survey. Neurology 1996; 46: 907-11. [CrossRef] 4. Hawkins SA, McDonell GV. Benign multiple sclerosis? Clinical course, long term follow up, and assessment of prognostic factors. J Neurol Neurosurg Psychiatry 1999; 67: 148-52. [CrossRef] 5. Ozakbas S, Turkoglu R, Tamam Y, Terzi M, Taskapilioglu O, Yucesan C, et al N. Prevalence of and risk factors for cognitive impairment in patients with relapsing-remitting multiple sclerosis: Multi-center, controlled trial. Mult Scler Relat Disord 2018; 22: 70-6. [CrossRef] 6. Tuzun E. Multipl skleroz patogenezinde B hücrelerinin rolü ve B hücre karşıtı monoklonal antikor tedavileri. Nöropsikiyatri Arşivi 2011; 48: 73-8. [CrossRef] 7. Sospedra M, Martin R. Immunology of multiple sclerosis. Annu Rev Immunol 2005; 23: 683-747. [CrossRef] 8. Naegelin Y, Naegelin P, von Felten S, Lorscheider J, Sonder J, Uitdehaag BMJ, et al. Association of Rituximab Treatment With Disability Progression Among Patients With Secondary Progressive Multiple Sclerosis JAMA Neurol 2019; 76: 274-81. [CrossRef] 9. Yamout BI, El-Ayoubi NK, Nicolas J, El Kouzi Y, Khoury SJ, Zeineddine MM.Safety and Efficacy of Rituximab in Multiple Sclerosis: A Retrospective Observational Study. J Immunol Res 2018; 2018: doi: 10.1155/2018/9084759. [CrossRef] 10. Achiron A, Feldman A, Magalashvili D, Dolev M, Gurevich M. Suppressed RNA-polymerase 1 pathway is associated with benign multiple sclerosis. PLoS One 2012; 7: doi: 10.1371/journal.pone.0046871. [CrossRef] 11. Yang J, Ren J, Yang Y, Sun J, Zhou X, Zheng S, et al. BANK1 alters B cell responses and influences the interactions between B cells and induced T regulatory cells in mice with collagen-induced arthritis. Arthritis Res Ther 2018; 20: 9. doi: 10.1186/s13075-017-1503-x. [CrossRef] 12. Kurtzke, J.F., A reassessment of the distribution of multiple sclerosis. Acta Neurologica Scandinavica 1975; 51: 110-36. [CrossRef] 13. Willer CJ, Dyment DA, Sadovnick AD, Ebers GC. Maternal-offspring HLA-DRB1 compatibility in multiple sclerosis. Tissue Antigens 2005; 66: 44-7. [CrossRef] 14. Düzgün N. İmmün Sistemin Tanıtımı. s: 97-122. Available from: URL: http://ichastaliklariromatoloji.medicine.ankara.edu.tr/files/2014/02/%C4%B0mm%C3%BCn-Sistemin-Tan%C4%B1t%C4%B1m%C4%B1.pdf 15. O’Connor BP, Raman VS, Erickson LD, Cook WJ, Weaver LK, Ahonen C, et al. BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med 2004; 199: 91-8. [CrossRef] 16. Aktura ŞD, Yılmaz V, Özkan-Yaşargün D, Ulusoy C, Tüzün E, Türkoğlu R. Peripheral blood memory B cell frequency predicts conversion from clinically isolated syndrome to multiple sclerosis. Mult Scler Relat Disord 2018; 23: 9-14. [CrossRef] 17. Komai T, Inoue M, Okamura T, Morita K, Iwasaki Y, Sumitomo S, et al. Transforming growth factor-β and interleukin-10 synergistically regulate humoral immunity via modulating metabolic signals. Front Immunol 2018; 9: 1364. doi: 10.3389/fimmu.2018.01364. [CrossRef] 18. Molnarfi N, Bjarnadóttir K, Benkhoucha M, Juillard C, Lalive PH. Activation of human B cells negatively regulates TGF-β1 production. J Neuroinflammation 2017; 14: 13. doi: 10.1186/s12974-017-0798-5. [CrossRef]
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Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Article
Authors

Melis Şen This is me

Recai Türkoğlu This is me

Erdem Tüzün This is me

Vuslat Yılmaz

Publication Date December 1, 2019
Submission Date November 18, 2019
Published in Issue Year 2019 Volume: 9 Issue: 3

Cite

Vancouver Şen M, Türkoğlu R, Tüzün E, Yılmaz V. B Cell Immunophenotyping and Expression Analysis of B Cell Specific Molecules of Patients with Benign Multiple Sclerosis. Experimed. 2019;9(3):105-12.