DAILY VARIABILITY IN SOLUBLE TOLL-LIKE RECEPTORS 2 IN THE SERUM OF WOMEN WITH RHEUMATOID ARTHRITIS: ITS ASSOCIATION WITH THE DISEASE

  • K. O. Zaichko NATIONAL PIROGOV MEMORIAL MEDICAL UNIVERSITY, VINNYTSYA
  • M. A. Stanislavchuk NATIONAL PIROGOV MEMORIAL MEDICAL UNIVERSITY, VINNYTSYA
  • N. V. Zaichko NATIONAL PIROGOV MEMORIAL MEDICAL UNIVERSITY, VINNYTSYA
Keywords: rheumatoid arthritis, toll-like receptor 2, circadian rhythms

Abstract

Introduction. Rheumatoid arthritis (RA) is a disease that associated with disorders of the circadian rhythms of proinflammatory mediators. Activation of immunoinflammatory and angiogenic processes in the synovium occurs with the participation of toll-like receptors 2 (TLR2). The study of the circadian rhythms of TLR2 productioin, in particular their soluble form (sTLR2) contained in biological fluids, will allow to personalize the prognosis of the disease and control the effectiveness of treatment in patients with RA.

The aim of the study – to find out the daily variability of sTLR2 in the serum of women with RA and to evaluate its association with the course of the disease.

Researh Methods. 173 patients with RA (100 % female) aged (43.7±7.35) years and 34 female of the control groups aged (42.4±10.5) years were examined. The diagnosis of RA was established by ACR/EULAR criteria 2010. Serum sTLR2 level was determined at 0800; 1400; 2000 and 0200 by Cloud-Clone Corp. (TLR2, SEA663Hu). The study was conducted in compliance with bioethical standards. Statistical processing of the results was performed in the SPSS22 application package.

Results and Discussion. Circadian oscillations of serum sTLR2 level with acrophase at 800 and batiphase at 2000 were found in healthy women. Patients with RA have circadian features of sTLR2 production: there is an increase in serum sTLR2 during the day (2 times) compared to the control group; variability in blood levels of sTLR2 in patients with RA is less significant, than in the control group; it was established a direct relationship between serum sTLR2 level, radiographic stage, and disease activity rates (DAS28, CDAI, HAQ, RAID).

Conclusions. Circadian variability of sTLR2 level in serum of women with RA and practically healthy subjects was established. In patients with RA, there is an increase in sTLR2 levels (more pronounced in the morning), which is associated with an increase in the severity of the disease.

References

Cutolo, M. (2016). Glucocorticoids and chrono­therapy in rheumatoid arthritis. RMD Open, 2 (1), e000203. doi: 10.1136/rmdopen-2015-000203. [PubMed].

Gibbs, J., & Ray, D. (2013). The role of the circadian clock in rheumatoid arthritis. Arthritis Research & Therapy, 15 (1), 205. doi: 10.1186/ar4146. [PubMed].

Kirwan, J., Clarke, L., Hunt, L., Perry, M., Straub, R., & Jessop, D. (2010). Effect of novel therapeutic glucocorticoids on circadian rhythms of hormones and cytokines in rheumatoid arthritis. Annals of The New York Academy Of Sciences, 1193 (1), 127-133. doi: 10.1111/ j.1749-6632.2009.05289.x. [PubMed].

Sierakowski, S., & Cutolo, M. (2011). Morning symptoms in rheumatoid arthritis: a defining characteristic and marker of active disease. Scandinavian Journal of Rheumatology, 40 (125), 1-5. doi: 10.3109/03009742. 2011.566433. [PubMed].

Radstake, T., Roelofs, M., Jenniskens, Y., Oppers-Walgreen, B., van Riel, P., & Barrera, P. (2004). Expression of Toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation by proinflammatory cytokines interleukin-12 and interleukin-18 via interferon-? Arthritis & Rheumatism, 50 (12), 3856-3865. doi: 10.1002/art.20678. [PubMed].

Hu, F., Li, Y., Zheng, L., Shi, L., Liu, H., & Zhang, X. (2014). Toll-Like receptors expressed by synovial fibro­blasts perpetuate Th1 and Th17 cell responses in rheu­matoid arthritis. Plos ONE, 9 (6), e100266. doi: 10.1371/journal.pone.0100266. [PubMed].

McGarry, T., Veale, D., Gao, W., Orr, C., Fearon, U., & Connolly, M. (2015). Toll-like receptor 2 (TLR2) induces migration and invasive mechanisms in rheumatoid arthri­tis. Arthritis Research & Therapy, 17 (1). doi: 10.1186/s13075-015-0664-8. [PubMed].

Langjahr, P., Díaz-Jiménez, D., De la Fuente, M., Rubio, E., Golenbock, D., & Bronfman, F. (2014). Metallo­proteinase-dependent TLR2 ectodomain shedding is involved in soluble toll-like receptor 2 (sTLR2) production. Plos ONE, 9 (12), e104624. doi: 10.1371/journal.pone.0104624. [PubMed].

Hossain, M., Morandi, E., Tanasescu, R., Fra­kich, N., Caldano, M., & Onion, D. (2018). The soluble form of toll-like receptor 2 is elevated in serum of multiple sclerosis patients: a novel potential disease biomarker. Frontiers in Immunology, 9. doi: 10.3389/fimmu.2018. 00457. [PubMed].

Houssen, M., El-Mahdy, R., & Shahin, D. (2014). Serum soluble toll-like receptor 2: a novel biomarker for systemic lupus erythematosus disease activity and lupus-related cardiovascular dysfunction. International Journal of Rheumatic Diseases, 19 (7), 685-692. doi: 10.1111/1756-185x.12452. [PubMed].

Silver, A., Buckley, S., Hughes, M., Hastings, A., Nitabach, M., & Fikrig, E. (2018). Daily oscillations in expression and responsiveness of Toll-like receptors in splenic immune cells. Heliyon, 4 (3), e00579. doi: 10.1016/j.heliyon.2018.e00579. [PubMed].

Aletaha, D., Neogi, T., Silman, A.J., Funovits, J., Felson, D.T., & Bingham, C.O. (2010) Rheumatoid arthritis classification criteria: an American College of Rheuma­tology/European League Against Rheumatism collabo­rative initiative. Ann. Rheum. Dis., (69), 1580-1588. [PubMed].

Hochberg, M., Chang, R., Dwosh, I., Lindsey, S., Pincus, T., & Wolfe, F. (1992). The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis & Rheumatism, 35 (5), 498-502. doi: 10.1002/art.1780350502. [PubMed].

Stanislavchuk, M., & Zaichko, K. (2019) Kros-kulturalna adaptatsiia ta validyzatsiia ukrainomovnoi versii RAID u khvorykh na revmatoidnyi artryt [Cross-cultural adaptation and validation of the Ukrainian version of RAID in patients with rheumatoid arthritis]. Ukrainskyi revma­tolohichnyi zhurnal – Ukrainian Journal of Rheumatology, 3 (77), 51-55 [in Ukrainian]

Gossec, L., Paternotte, S., Aanerud, G., Bala­nescu, A., Boumpas, D., & Carmona, L. (2011). Fina­lisation and validation of the rheumatoid arthritis impact of disease score, a patient-derived composite measure of impact of rheumatoid arthritis: a EULAR initiative. Annals of the Rheumatic Diseases, 70 (6), 935-942. doi: 10.1136/ard.2010.142901. [PubMed].

Sokka, T., Toloza, S., Cutolo, M., Kautiainen H., Makinen H., & Gogus F. (2009). Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA Study. Arthritis Research & Therapy, 11 (7). doi:10.1186/ar2591. [PubMed].

Yan, L., & Silver, R. (2016). Neuroendocrine underpinnings of sex differences in circadian timing sys­tems. The Journal of Steroid Biochemistry and Molecular Biology, 160, 118-126. doi: 10.1016/j.jsbmb.2015.10.007. [PubMed].

Lacerte, P., Brunet, A., Egarnes, B., Duchêne, B., Brown, J., & Gosselin, J. (2016). Overexpression of TLR2 and TLR9 on monocyte subsets of active rheumatoid arthritis patients contributes to enhance responsiveness to TLR agonists. Arthritis Research & Therapy, 18 (1). doi: 10.1186/s13075-015-0901-1. [PubMed].

Cho, M., Ju, J., Kim, H., Oh, H., Kang, C., & Jhun, J. (2007). Toll-like receptor 2 ligand mediates the upregulation of angiogenic factor, vascular endothelial growth factor and interleukin-8/CXCL8 in human rheu­matoid synovial fibroblasts. Immunology Letters, 108 (2), 121-128. doi: 10.1016/j.imlet.2006.11.005. [PubMed].

Saber, T., Veale, D., Balogh, E., McCormick, J., NicAnUltaigh, S., Connolly, M., & Fearon, U. (2011). Toll-like receptor 2 induced angiogenesis and invasion is mediated through the tie2 signalling pathway in rheu­matoid arthritis. Plos ONE, 6 (8), e23540. doi: 10.1371/journal.pone.0023540. [PubMed].

Kim, H., Kim, K., Kim, B., Cho, M., & Lee, S. (2015). The effect of vascular endothelial growth factor on osteoclastogenesis in rheumatoid arthritis. PLOS ONE, 10(4), e0124909. doi: 10.1371/journal.pone. 0124909. [PubMed].

Published
2020-01-30
How to Cite
Zaichko, K. O., Stanislavchuk, M. A., & Zaichko, N. V. (2020). DAILY VARIABILITY IN SOLUBLE TOLL-LIKE RECEPTORS 2 IN THE SERUM OF WOMEN WITH RHEUMATOID ARTHRITIS: ITS ASSOCIATION WITH THE DISEASE. Medical and Clinical Chemistry, (4), 5-12. https://doi.org/10.11603/mcch.2410-681X.2019.v.i4.10820
Section
ORIGINAL INVESTIGATIONS