Brief Communication
 

Quantitative Evaluation of BAFF, HMGB1, TLR 4 AND TLR 7 Expression in Patients with Relapsing Remitting Multiple Sclerosis

Abstract

Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by a complex immune response. Because of the complex nature of MS pathogenesis, a panel of biomarkers derived from different platforms will be required to reflect disease-related alterations. Monitoring and evaluation of molecules associated with the pathogenesis of the disease would provide useful information on disease progression and therapeutic assessment. In view of this, we evaluated the mRNA expression levels of B-cell activating factor (BAFF), high mobility group box 1 (HMGB-1), Toll like receptor (TLR) 4 and TLR7 in MS. These molecules are implicated in the pathogenesis of MS; however, they havereceived little attention. PBMCs were isolated from whole blood of 84 Relapsing Remitting Multiple Sclerosis patients and 70 healthy controls. Relative quantitative RT-PCR was applied to quantify the transcriptional levels of the immune markers. The mRNA expression levels of TLR7 were significantly elevated in RRMS patients than healthy controls. Whereas, TLR4 expression was found to be significantly lower in the patients than control group. We found no difference analyzing the mRNA levels of BAFF and HMGB1. Our data highlights the immune marker correlates in RRMS patients. However, further in-depth studies are warranted to check for their reliability of biomarkers in autoimmune diseases such as MS.

1. Srivastava P, Mujtaba A, Singhal M. “Gene and Cytokines expression of Multiple Sclerosis and its therapeutic regimen: A Systemic Review”, Int J Drug Dev & Res 2012; 4(3): 55-66.

2. Stadelmann C. Multiple sclerosis as a neurodegenerative disease: pathology, mechanisms and therapeutic implications. Curr Opin Neurol 2011; 24(3):224-9.

3. Oksenberg JR, Baranzini SE, Sawcer S, Hauser SL. The genetics of multiple sclerosis: SNPs to pathways to pathogenesis. Nat Rev Genet 2008; 9(7):516–26.

4. Compston A, Coles A. Multiple sclerosis. Lancet 2008;372(9648):1502–17.

5. Sahraian MA, Khorramnia S, Ebrahim MM, Moinfar Z, Lotfi J, Pakdaman H. Multiple sclerosis in Iran: a demographic study of 8,000 patients and changes over time. Eur Neurol 2010; 64(6):331–6.

6. Tolou-Ghamari Z. A Review of Geoepidemiological Differences of Multiple Sclerosis in Iran and Other Middle East Countries. Arch Neurosci 2015; 2(3):e22028.

7. Etemadifar M, Maghzi AH. Sharp increase in the incidence and prevalence of multiple sclerosis in Isfahan, Iran. Mult Scler 2011; 17(8):1022–7.

8. Etemadifar M, Abtahi SH. Multiple sclerosis in Isfahan, Iran: Past, Present and Future. Int J Prev Med 2012;3(5):301–2.

9. Etemadifar M, Sajjadi S, Nasr Z, Firoozeei TS, Abtahi SH, Akbari M, et al. Epidemiology of multiple sclerosis in Iran: a systematic review. Eur Neurol 2013; 70(5-6):356-63.

10. Vosoughi R, Freedman MS. Review of Therapy of MS.Clin Neurol and Neurosurg 2010; 112(5):365-85.

11. Martins TB, Rose JW, Jaskowski TD, Wilson AR, Husebye D, Seraj HS, et al. Analysis of proinflammatory and anti-Inflammatory cytokine serum concentrations in patients with Multiple Sclerosis by using a Multiplexed Immunoassay. Am J Clin Pathol 2011; 136(5):696-704.

12. Batoulis H, Addicks K, Kuerten S. Emerging concepts in autoimmune encephalomyelitis beyond the CD4/T (H)1 paradigm. Ann Anat 2010; 192(4):179-93.

13. Ramagopalan SV, Dobson R, Meier UC, Giovannoni G.Multiple sclerosis: risk factors, prodromes, and potential causal pathways. Lancet Neurol 2010; 9(7):727-39.

14. Romme Christensen J, Börnsen L, Hesse D, Krakauer M, Sørensen PS, Søndergaard HB, et al. Cellular sources of dysregulated cytokines in relapsing-remitting multiple sclerosis. J Neuroinflammation 2012; 9:215.

15. Kunz M, Ibrahim SM. Cytokines and cytokine profiles in human autoimmune diseases and animal models of autoimmunity. Mediators Inflamm 2009; 2009:979258.

16. Martins TB, Anderson JL, Muhlestein JB, Horne BD, Carlquist JF, Roberts WL, et al. Risk factor analysis of plasma cytokines in patients with coronary artery disease by a multiplexed fluorescent immunoassay. Am J Clin Pathol 2006; 125(6):906-13.

17. Katsavos S, Anagnostouli M. Biomarkers in Multiple Sclerosis: An Up-to-Date Overview. Mult Scler Int 2013;2013:340508.

18. Holmøy T, Løken-Amsrud KI, Bakke SJ, Beiske AG, Bjerve KS, Hovdal H, et al. Inflammation markers in Multiple Sclerosis: CXCL16 reflects and may also predict disease activity. PLoS ONE 2013; 8(9):e75021.

19. Kreuzaler M, Rauch M, Salzer U, Birmelin J, Rizzi M, Grimbacher B, et al. Soluble BAFF levels inversely correlate with peripheral B cell numbers and the expression of BAFF receptors. J Immunol 2012;188 (1):497–503.

20. Vincent FB, Morand EF, Mackay F. BAFF and innate immunity: new therapeutic targets for systemic lupus erythematosus. Immunol Cell Biol 2012; 90(3):293-303.

21. Kalled SL, Ambrose C, Hsu YM. The biochemistry and biology of BAFF, APRIL and their receptors. Curr Dir Autoimmun 2005; 8:206-42.

22. Mongini PK, Inman JK, Han H, Kalled SL, Fattah RJ, McCormick S. Innate immunity and human B cell clonal expansion: effects on the recirculating B2 subpopulation. J Immunol 2005; 175(9):6143-54.

23. Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, et al. "HMG-1 as a late mediator of endotoxin lethality in mice". Science 1999; 285(5425):248-51

24. Racke MK, Drew PD. Toll-Like receptors in multiple sclerosis. Curr Top Microbiol Immunol 2009; 336:155–68.

25. Derkow K, Bauer JM, Hecker M, Paap BK, Thamilarasan M, Koczan D, et al. Multiple Sclerosis: Modulation of Toll-Like Receptor (TLR) Expression by Interferon-β Includes Upregulation of TLR7 in Plasmacytoid Dendritic Cells. PLoS ONE 2013; 8(8):e70626.

26. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteriafor multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001; 50(1):121-7.

27. Podda G, Nyirenda M, Crooks J, Gran B. Innate immune responses in the CNS: role of toll-like receptors, mechanisms, and therapeutic opportunities in multiple sclerosis. J Neuroimmune Pharmacol 2013; 8(4):791-806.

28. Thangarajh M, Gomes A, Masterman T, Hillert J, Hjelmström P. Expression of B-cell-activating factor of the TNF family (BAFF) and its receptors in multiple sclerosis. J Neuroimmunol 2004; 152(1-2):183-90.

29. Huard B, Arlettaz L, Ambrose C, Kindler V, Mauri D, Roosnek E, et al. BAFF production by antigen-presenting cells provides T cell co-stimulation. Int Immunol 2004;16(3):467-75.

30. Andersson A, Covacu R, Sunnemark D, Danilov AI, Dal Bianco A, Khademi M, et al. Pivotal Advance: HMGB1 expression in active lesions of human and experimental multiple sclerosis. J Leukoc Biol 2008; 84(5):1248–55.

31. Miranda-Hernandez S, Baxter AG. Role of toll-like receptors in multiple sclerosis Am J Clin Exp Immunol 2013; 2(1):75-93.

32. Vaure C, Liu Y. A comparative review of toll-like receptor 4 expression and functionality in different animal species. Front immunol 2014; 5:316.

Files
IssueVol 15, No 1 (2016) QRcode
SectionBrief Communication
Keywords
Biomarkers Cytokines HMGB proteins Inflammation Multiple sclerosis RNA messenger

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Hamid K, Nejati A, Shoja Z, Mollaei-Kandelousd Y, Doosti R, Mirshafiey A, Tafakhori A, Sahraian MA, Marashi SM. Quantitative Evaluation of BAFF, HMGB1, TLR 4 AND TLR 7 Expression in Patients with Relapsing Remitting Multiple Sclerosis. Iran J Allergy Asthma Immunol. 2016;15(1):75-81.