Yıl: 2021 Cilt: 11 Sayı: 1 Sayfa Aralığı: 33 - 37 Metin Dili: İngilizce DOI: 10.26650/experimed.2021.888583 İndeks Tarihi: 03-12-2021

Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis

Öz:
Objective: We have previously shown altered blood B cells in the first attack blood samples of clinically isolated syndrome (CIS) patients, who converted to multiple sclerosis (MS). Our aim was to investigate levels of B cell receptor (BCR)-associated genes expression in converting CIS (CIS-c) and non-converting CIS patients (CISnc) with a 5-year follow-up. Methods: Seven CIS-c patients, 12 CIS-nc patients and 10 agesex matched healthy donors were enrolled in this study. RNA was extracted from frozen peripheral blood cells of subjects that were obtained in the first attack using a RNA isolation kit. Expression levels of B-cell adaptor protein with ankyrin repeats 1 (BANK1), B lymphocyte kinase (BLK) and Fc receptor-like protein 2 (FCRL2) genes were evaluated samples by real-time polymerase chain reaction (RT-PCR). Results: CIS-nc patients showed elevated BANK1, BLK and FCRL2 gene expression levels as compared to CIS-c patients and healthy controls. Conclusions: Expression levels of the genes that inhibit BCR signaling are increased in CIS-nc, suggesting that inhibiting exaggerated B cell response by optimization of B cell proliferation may prevent the progression of clinically isolated syndrome to MS.
Anahtar Kelime:

B Hücre Reseptör (BHR) Sinyal Yolağı Faktörlerinin Ekspresyon Düzeyleri Klinik İzole Sendromdan Multipl Skleroza Dönüşümle İlişkilidir

Öz:
Amaç: Daha önceki çalışmalarımızda, multipl skleroza (MS) dönüşen klinik izole sendrom (KİS) olgularının ilk atakta alınan kan örneklerinde periferik kan B hücre düzeylerinin değiştiğini gösterilmiştir. Bu çalışmada beş yıllık takipte MS’e dönüşen ve dönüşmeyen KİS olgularında B hücre reseptör (BHR) ilişkili genlerin ekspresyon düzeylerinin araştırılması amaçlanmıştır. Yöntem: Yedi MS’e dönüşen, 12 MS’e dönüşmeyen KİS olgusu ile yaş ve cinsiyet açısından eşleştirilmiş 10 sağlıklı donör çalışmaya dahil edildi. İlk atak döneminde elde edilen donmuş periferik kan mononükleer hücrelerinden (PKMH) RNA izolasyon kiti kullanılarak total RNAlar izole edildi. Örneklerden gerçek zamanlı polimeraz zincir reaksiyonu (RT-PCR) yöntemi ile ankrin tekrarlı B-hücre adaptör proteini (BANK1), B lenfosit kinaz (BLK), Fc reseptör benzeri protein 2 (FCRL2) genlerinin ekspresyonları değerlendirildi. Bulgular: MS’e dönüşmeyen KİS olgularında BANK1, BLK ve FCRL2 gen ekspresyon düzeyleri MS’e dönüşen KİS olguları ve sağlıklı kontrollere kıyasla artmış olarak saptandı. Sonuç: BHR sinyalizasyonunu inhibe eden gen ekspresyonlarının MS’e dönüşmeyen olgularda artması, abartılı B hücre yanıtının B hücre proliferasyonunun optimize edilmesi yoluyla baskılanmasının KİS’ten MS’e ilerleyişi engelleyebileceğini düşündürmüştür.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med 2000; 343(13): 938-52. [CrossRef ]
  • 2. Yadav SK, Mindur JE, Ito K, Dhib-Jalbut S. Advances in the immunopathogenesis of multiple sclerosis. Curr Opin Neurol 2015; 28(3): 206-19. [CrossRef ]
  • 3. Serafini B, Rosicarelli B, Magliozzi R, Stigliano E, Aloisi F. Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 2004; 14(2): 164-74. [CrossRef ]
  • 4. Bar-Or A, Fawaz L, Fan B, Darlington PJ, Rieger A, Ghorayeb C, et al. Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS? Ann Neurol 2010; 67(4): 452-61. [CrossRef ]
  • 5. Fisniku LK, Brex PA, Altmann DR, Miszkiel KA, Benton CE, Lanyon R, et al. Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 2008; 131(Pt 3): 808- 17. [CrossRef ]
  • 6. Brettschneider J, Czerwoniak A, Senel M, Fang L, Kassubek J, Pinkhardt E, et al. The chemokine CXCL13 is a prognostic marker in clinically isolated syndrome (CIS). PLoS One 2010; 5(8): e11986. [CrossRef ]
  • 7. Aktura SD, Yilmaz V, Ozkan-Yasargun D, Ulusoy C, Tuzun E, Turkoglu 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 ]
  • 8. Åkerblad P, Sigvardsson M. Early B cell factor is an activator of the B lymphoid kinase promoter in early B cell development. The Journal of Immunology 1999; 163(10): 5453-61.
  • 9. Yokoyama K, Su Ih IH, Tezuka T, Yasuda T, Mikoshiba K, Tarakhovsky A, et al. BANK regulates BCR-induced calcium mobilization by promoting tyrosine phosphorylation of IP(3) receptor. EMBO J 2002; 21(1-2): 83-92. [CrossRef ]
  • 10. Chikaev NA, Bykova EA, Najakshin AM, Mechetina LV, Volkova OY, Peklo MM, et al. Cloning and characterization of the human FCRL2 gene. Genomics 2005; 85(2): 264-72. [CrossRef ]
  • 11. Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the Mc- Donald criteria. Lancet Neurol 2018; 17(2): 162-73. [CrossRef ]
  • 12. Gauld SB, Dal Porto JM, Cambier JC. B cell antigen receptor signaling: roles in cell development and disease. Science 2002; 296(5573): 1641-2. [CrossRef ]
  • 13. Aiba Y, Yamazaki T, Okada T, Gotoh K, Sanjo H, Ogata M, et al. BANK negatively regulates Akt activation and subsequent B cell responses. Immunity 2006; 24(3): 259-68. [CrossRef ]
  • 14. Islam KB, Rabbani H, Larsson C, Sanders R, Smith CI. Molecular cloning, characterization, and chromosomal localization of a human lymphoid tyrosine kinase related to murine Blk. J Immunol 1995; 154(3): 1265-72.
  • 15. Bernal-Quiros M, Wu YY, Alarcon-Riquelme ME, Castillejo-Lopez C. BANK1 and BLK act through phospholipase C gamma 2 in B-cell signaling. PLoS One 2013; 8(3): e59842. [CrossRef ]
  • 16. Samuelson EM, Laird RM, Papillion AM, Tatum AH, Princiotta MF, Hayes SM. Reduced B lymphoid kinase (Blk) expression enhances proinflammatory cytokine production and induces nephrosis in C57BL/6-lpr/lpr mice. PLoS One 2014; 9(3): e92054. [CrossRef ]
  • 17. Delgado-Vega AM, Dozmorov MG, Quiros MB, Wu YY, Martinez- Garcia B, Kozyrev SV, et al. Fine mapping and conditional analysis identify a new mutation in the autoimmunity susceptibility gene BLK that leads to reduced half-life of the BLK protein. Ann Rheum Dis 2012; 71(7): 1219-26. [CrossRef ]
  • 18. Matesanz-Isabel J, Sintes J, Llinas L, de Salort J, Lazaro A, Engel P. New B-cell CD molecules. Immunol Lett 2011; 134(2): 104-12. [CrossRef ]
  • 19. Jackson TA, Haga CL, Ehrhardt GR, Davis RS, Cooper MD. FcR-like 2 Inhibition of B cell receptor-mediated activation of B cells. J Immunol 2010; 185(12): 7405-12. [CrossRef ]
  • 20. Shabani M, Bayat AA, Jeddi-Tehrani M, Rabbani H, Hojjat-Farsangi M, Ulivieri C, et al. Ligation of human Fc receptor like-2 by monoclonal antibodies down-regulates B-cell receptor-mediated signalling. Immunology 2014; 143(3): 341-53. [CrossRef ]
  • 21. Comabella M, Canto E, Nurtdinov R, Rio J, Villar LM, Picon C, et al. MRI phenotypes with high neurodegeneration are associated with peripheral blood B-cell changes. Hum Mol Genet 2016; 25(2): 308-16. [CrossRef ]
APA Karaaslan Z, Akbayır E, Şanlı E, Şen M, Yüceer H, Kucukali C, Tuzun E, Türkoğlu R (2021). Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis. , 33 - 37. 10.26650/experimed.2021.888583
Chicago Karaaslan Zerrin,Akbayır Ece,Şanlı Elif,Şen Melis,Yüceer Hande,Kucukali Cem Ismail,Tuzun Erdem,Türkoğlu Recai Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis. (2021): 33 - 37. 10.26650/experimed.2021.888583
MLA Karaaslan Zerrin,Akbayır Ece,Şanlı Elif,Şen Melis,Yüceer Hande,Kucukali Cem Ismail,Tuzun Erdem,Türkoğlu Recai Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis. , 2021, ss.33 - 37. 10.26650/experimed.2021.888583
AMA Karaaslan Z,Akbayır E,Şanlı E,Şen M,Yüceer H,Kucukali C,Tuzun E,Türkoğlu R Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis. . 2021; 33 - 37. 10.26650/experimed.2021.888583
Vancouver Karaaslan Z,Akbayır E,Şanlı E,Şen M,Yüceer H,Kucukali C,Tuzun E,Türkoğlu R Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis. . 2021; 33 - 37. 10.26650/experimed.2021.888583
IEEE Karaaslan Z,Akbayır E,Şanlı E,Şen M,Yüceer H,Kucukali C,Tuzun E,Türkoğlu R "Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis." , ss.33 - 37, 2021. 10.26650/experimed.2021.888583
ISNAD Karaaslan, Zerrin vd. "Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis". (2021), 33-37. https://doi.org/10.26650/experimed.2021.888583
APA Karaaslan Z, Akbayır E, Şanlı E, Şen M, Yüceer H, Kucukali C, Tuzun E, Türkoğlu R (2021). Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis. EXPERIMED, 11(1), 33 - 37. 10.26650/experimed.2021.888583
Chicago Karaaslan Zerrin,Akbayır Ece,Şanlı Elif,Şen Melis,Yüceer Hande,Kucukali Cem Ismail,Tuzun Erdem,Türkoğlu Recai Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis. EXPERIMED 11, no.1 (2021): 33 - 37. 10.26650/experimed.2021.888583
MLA Karaaslan Zerrin,Akbayır Ece,Şanlı Elif,Şen Melis,Yüceer Hande,Kucukali Cem Ismail,Tuzun Erdem,Türkoğlu Recai Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis. EXPERIMED, vol.11, no.1, 2021, ss.33 - 37. 10.26650/experimed.2021.888583
AMA Karaaslan Z,Akbayır E,Şanlı E,Şen M,Yüceer H,Kucukali C,Tuzun E,Türkoğlu R Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis. EXPERIMED. 2021; 11(1): 33 - 37. 10.26650/experimed.2021.888583
Vancouver Karaaslan Z,Akbayır E,Şanlı E,Şen M,Yüceer H,Kucukali C,Tuzun E,Türkoğlu R Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis. EXPERIMED. 2021; 11(1): 33 - 37. 10.26650/experimed.2021.888583
IEEE Karaaslan Z,Akbayır E,Şanlı E,Şen M,Yüceer H,Kucukali C,Tuzun E,Türkoğlu R "Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis." EXPERIMED, 11, ss.33 - 37, 2021. 10.26650/experimed.2021.888583
ISNAD Karaaslan, Zerrin vd. "Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis". EXPERIMED 11/1 (2021), 33-37. https://doi.org/10.26650/experimed.2021.888583