Tenascin-C and Interleukin-17 Up-regulation in Axial Spondyloarthritis Patients
Vol. 30 No. 4 (2022), Original Articles
Vol. 30 No. 4 (2022)

Tenascin-C and Interleukin-17 Up-regulation in Axial Spondyloarthritis Patients

Original Articles
https://doi.org/10.35465/30.4.2022.pp3-11
Published March 6, 2023
Mohammed S. Al-Hindawi
Applied Sciences Department, Applied Chemists Division, University of Technology, 10001 Baghdad, Iraq
https://orcid.org/0000-0003-1487-5943
Abdulnasser M. Al-Gebori
Applied Sciences Department, Applied Chemists Division, University of Technology, 10001 Baghdad, Iraq
https://orcid.org/0000-0002-4038-282X
Mohammed Hadi Munshed Alosami
Department of Medicine, Rheumatology Unit, Colleges of Medicine, University of Baghdad, 10001 Baghdad, Iraq
https://orcid.org/0000-0001-8521-5876
PDF EN

Keywords

Axial spondyloarthritis; Tenascin-C; Interleukin-17; BASDAI.

How to Cite

Al-Hindawi, M., Al-Gebori, A., & Alosami, M. (2023). Tenascin-C and Interleukin-17 Up-regulation in Axial Spondyloarthritis Patients. Rheumatology (Bulgaria), 30(4), 3-11. https://doi.org/10.35465/30.4.2022.pp3-11
ACM ACS APA ABNT Chicago Harvard IEEE MLA Turabian Vancouver

Download Citation

Endnote/Zotero/Mendeley (RIS) BibTeX

Abstract

Background: Axial spondyloarthritis (axSpA) is an inflammatory, systemic rheumatic condition that mostly affects the axial skeleton. Tenascin-C (TN-C) is a hexameric glycoprotein of considerable size, upregulated in many inflammatory conditions, while Interleukin-17 (IL-17) a cytokine that plays an important role in SpA symptoms. Objective: to investigate the upregulation between the serum levels of TN-C and IL-17 in Iraqi axSpA patients and the disease characteristics. Patients and Methods: Seventy-four axSpA patients and 28 matched controls were studied. Fifty-four patients received a tumor necrosis factor inhibitor (TNFi) and 20 did not. Serum TN-C and IL-17 concentrations were determined using the ELISA technique. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was assessed. For statistical tests, Chi Square, Mann Whitney, Independent Samples T, and Pearson's correlation tests are used. Results: Patients mean age was 35.6±0.9 years, 65 males and 9 females, and disease duration was 5.18±0.6 years. 47.4% were smokers, 47% had inflammatory low back pain, and HLA-B27 was present in 91%. BASDAI mean was 6.1±0.4 in non-TNFi and 2.6±0.3 in those on TNFi. The serum TN-C concentration was significantly increased in patients, especially those on non-TNFi (79±9.6 pg/mL) compared to those on TNFi (69.1±3.2 pg/mL) and control (53±3.9 pg/mL) (p=0.003). Serum IL-17 was significantly elevated in those receiving TNFi (877.9±257 pg/mL) compared to non-TNFi (487.2±234 pg/mL) and control (182.4±36.6 pg/mL) (p=0.033). The TN-C significantly correlated with erythrocyte sedimentation rate (r=0.27, p=0.02) and with hemoglobin (Hb) concentration (r=0.26, p=0.02). TN-C and IL-17 were non-significantly related (r=0.14, p=0.2). Conclusions: axSpA Patients demonstrated high levels of serum TN-C, particularly in those not receiving TNFi, and high IL-17 levels in those receiving TNFi, suggesting that there is an association with tissue injury from the disease and stimulation of immunological and resident tissue cells. Patients who had not received TNFi showed significantly higher disease activity than others.

https://doi.org/10.35465/30.4.2022.pp3-11
PDF EN

References

  1. Deodhar A, van der Heijde D, Gensler LS, Kim TH, Maksymowych WP, Østergaard M, et al. Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial. Lancet. 2020;395(10217):53-64. DOI:10.1016/S0140-6736(19)32971-X.
  2. Sakr BR, Mohamed HE, Effat DA. Relationship of adherence to treatment with disease activity, physical function, quality of life, treatment satisfaction and beliefs in axial spondyloarthritis patients. Egypt Rheumatol. 2022;44(3):191-195. DOI:10.1016/j.ejr.2021.12.001.
  3. Navarro-Compán V. An update on diagnosis and classification of axial spondyloarthritis. Curr Rheumatol Rep. 2019;21(8):1-7. DOI:10.1007/s11926-019-0838-5.
  4. Michelena X, López-Medina C, Marzo-Ortega H. Non-radiographic versus radiographic axSpA: what’s in a name?. Rheumatol (United Kingdom). 2020;59:18-24. DOI:10.1093/rheumatology/keaa422.
  5. Midwood KS, Hussenet T, Langlois B, Orend G. Advances in tenascin-C biology. Cell Mol Life Sci. 2011;68(19):3175-3199. DOI:10.1007/s00018-011-0783-6
  6. Zuliani-Alvarez L, Marzeda AM, Deligne C, Schwenzer A, McCann FE, Marsden BD, et al. Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers. Nat Commun. 2017;8(1):1-4. DOI:10.1038/s41467-017-01718-7.
  7. Chiquet M. Tenascin-C: From discovery to structure-function relationships. Front Immunol. 2020;11:611789. DOI:10.3389/fimmu.2020.611789.
  8. Li Z, Chen S, Cui H, Li X, Chen D, Hao W, et al. Tenascin-C-mediated suppression of extracellular matrix adhesion force promotes entheseal new bone formation through activation of Hippo signalling in ankylosing spondylitis. Ann Rheum Dis. 2021;80(7):891-902. DOI:10.1136/annrheumdis-2021-220002.
  9. Gupta L, Bhattacharya S, Aggarwal A. Tenascin-C, a biomarker of disease activity in early ankylosing spondylitis. Clin Rheumatol. 2018;37(5):1401-1405. DOI:10.1007/s10067-017-3938-5.
  10. Page TH, Charles PJ, Piccinini AM, Nicolaidou V, Taylor PC, Midwood KS. Raised circulating tenascin-C in rheumatoid arthritis. Arthritis Res Ther. 2012;14(6):1-9. DOI:10.1186/ar4105.
  11. Al-Gebori AM, Alosami MH, Al-Hashimi NH. Prevalence of 25-hydroxy vitamin D deficiency and some biochemical parameters in Iraqi patients with rheumatoid arthritis and their associations with disease activity. Asian J Pharm Clin Res. 2020;13(4):132-136. DOI:10.22159/ajpcr.2020.v13i4.36759.
  12. Al-Hashimi NH, Al-Gebori AM, Alosami MH. Evaluation of the Human Pulmonary Activation-Regulated Chemokine (CCL18/PARC) and Alkaline Phosphatase (ALP) Levels in Iraqi Patients with Rheumatoid Arthritis. Iraqi J Sci. 2020,26:713-719. DOI:10.24996/ijs.2020.61.4.1
  13. Sulaiman GM, Al-ansari RF, AL-Gebori AM, Khalil KA, Albukhaty S, Ahmed EM, et al. Serum Levels of Interleukin 10, Interleukin 17A, and Calcitriol in Different Groups of Colorectal Cancer Patients. Jordan J Biol Sci. 2022;15(1):75-81. DOI:10.54319/jjbs/150110.
  14. Sieper J, Poddubnyy D, Miossec P. The IL-23–IL-17 pathway as a therapeutic target in axial spondyloarthritis. Nat Rev Rheumatol. 2019;15(12):747-757. DOI:10.1038/s41584-019-0294-7.
  15. Torgutalp M, Poddubnyy D. IL-17 inhibition in axial spondyloarthritis: current and future perspectives. Expert Opin Biol Ther. 2019;19(7):631-641. DOI:10.1080/14712598.2019.1605352.
  16. Elsayed EK, El-Saadany HM, Elfar NN, El-Khouly RM, Almaidany SH, Gaber RA. Association of interleukin-17 with peripheral spondyloarthropathic changes detected by musculoskeletal ultrasound in psoriatic patients. Egypt Rheumatol. 2020;42(4):303-307. DOI:10.1016/j.ejr.2019.04.011
  17. Rudwaleit M, Van Der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 2009;68(6):777-783. DOI:10.1136/ard.2009.108233.
  18. Calin A, Nakache JP, Gueguen A, Zeidler H, Mielants H, Dougados M. Defining disease activity in ankylosing spondylitis: is a combination of variables (Bath Ankylosing Spondylitis Disease Activity Index) an appropriate instrument?. Rheumatology. 1999;38(9):878-882. DOI:10.1093/rheumatology/38.9.878.
  19. Udalova IA, Ruhmann M, Thomson SJ, Midwood KS. Expression and immune function of tenascin-C. Crit Rev Immunol. 2011;31(2),115-145. DOI:10.1615/CritRevImmunol.v31.i2.30
  20. Midwood KS, Orend G. The role of tenascin-C in tissue injury and tumorigenesis. J Cell Commun Signal. 2009;3(3):287-310. DOI:10.1007/s12079-009-0075-1.
  21. Midwood K, Sacre S, Piccinini AM, Inglis J, Trebaul A, Chan E, et al. Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nat Med. 2009;15(7):774-780. DOI:10.1038/nm.1987.
  22. Bubová K, Prajzlerova K, Hulejova H, Gregova M, Mintálová K, Husakova M et al. Elevated tenascin-C serum levels in patients with axial spondyloarthritis. Physiol Res. 2020;69(4):653-660. DOI:10.33549/physiolres.934414.
  23. Ruhmann M, Piccinini AM, Kong PL, Midwood KS. Endogenous activation of adaptive immunity: tenascin-C drives interleukin-17 synthesis in murine arthritic joint disease. Arthritis Rheum. 2012;64(7):2179-2190. DOI:10.1002/art.34401.
  24. Van Mechelen M, Lories R. Tenascin-C, a novel target to inhibit new bone formation in axial spondyloarthritis, linked with inflammation, mechanical strain and tissue damage. Ann Rheum Dis. 2021;80(7):823-824. DOI:10.1136/annrheumdis-2021-220443
  25. Wendling D, Cedoz JP, Racadot E, Dumoulin G. Serum IL-17, BMP-7, and bone turnover markers in patients with ankylosing spondylitis. Jt Bone Spine. 2007;74(3):304-305. DOI:10.1016/j.jbspin.2006.11.005.
  26. Mei Y, Pan F, Gao J, Ge R, Duan Z, Zeng Z, et al. Increased serum IL-17 and IL-23 in the patient with ankylosing spondylitis. Clin Rheumatol. 2011;30(2):269-273. DOI:10.1007/s10067-010-1647-4.
  27. DeLay ML, Turner MJ, Klenk EI, Smith JA, Sowders DP, Colbert RA. HLA–B27 misfolding and the unfolded protein response augment interleukin‐23 production and are associated with Th17 activation in transgenic rats. Arthritis Rheum. 2009;60(9):2633-2643. DOI:10.1002/art.24763.
  28. Babaie F, Hasankhani M, Mohammadi H, Safarzadeh E, Rezaiemanesh A, Salimi R, et al. The role of gut microbiota and IL-23/IL-17 pathway in ankylosing spondylitis immunopathogenesis: New insights and updates. Immunol Lett. 2018;196:52-62. DOI:10.1016/j.imlet.2018.01.014.
  29. van der Heijde D, Wei JC, Dougados M, Mease P, Deodhar A, Maksymowych WP, et al. Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial. Lancet. 2018;392(10163):2441-2451. DOI:10.1016/S0140-6736(18)31946-9.
  30. Akiyama S, Sakuraba A. Distinct roles of interleukin-17 and T helper 17 cells among autoimmune diseases. J Transl Autoimmun. 2021;4:100-104. DOI:10.1016/j.jtauto.2021.100104.
  31. Momčilović M, Stamenković V, Jovanović M, Andjus PR, Jakovčevski I, Schachner M, et al. Tenascin-C deficiency protects mice from experimental autoimmune encephalomyelitis. J Neuroimmunol. 2017;302:1-6. DOI:10.1016/j.jneuroim.2016.12.001.
  32. Taams LS, Steel KJ, Srenathan U, Burns LA, Kirkham BW. IL-17 in the immunopathogenesis of spondyloarthritis. Nat Rev Rheumatol. 2018;14(8):453-466. DOI:10.1038/s41584-018-0044-2.
  33. Machino‐Ohtsuka T, Tajiri K, Kimura T, Sakai S, Sato A, Yoshida T, et al. Tenascin‐C aggravates autoimmune myocarditis via dendritic cell activation and Th17 cell differentiation. J Am Heart Ass. 2014;3(6):e001052. DOI:10.1161/JAHA.114.001052.
  34. Boers N, Michielsens CA, Van Der Heijde D, Den Broeder AA, Welsing PM. The effect of tumour necrosis factor inhibitors on radiographic progression in axial spondyloarthritis: a systematic literature review. Rheumatology. 2019;58(11):1907-1922. DOI:10.1093/rheumatology/kez363.
  35. Huang Y, Deng W, Zheng S, Feng F, Huang Z, Huang Q, et al. Relationship between monocytes to lymphocytes ratio and axial spondyloarthritis. Int Immunopharmacol.2018;57:43-46. DOI:10.1016/j.intimp.2018.02.008.
  36. Brown MA, Li Z, Cao KA. Biomarker development for axial spondyloarthritis. Nat Rev Rheumatol.2020;16(8):448-463. DOI:10.1038/s41584-020-0450-0.
  37. Wang J, Su J, Yuan Y, Jin X, Shen B, Lu G. The role of lymphocyte-monocyte ratio on axial spondyloarthritis diagnosis and sacroiliitis staging. BMC Musculoskelet Disord. 2021;22(1):1-9. DOI:10.1186/s12891-021-03973-8
  38. Gracey E, Yao Y, Green B, Qaiyum Z, Baglaenko Y, Lin A, et al. Sexual dimorphism in the Th17 signature of ankylosing spondylitis. Arthritis Rheumatol. 2016;68(3):679-689. DOI:10.1002/art.39464.
  39. Rusman T, van Bentum RE, Van der Horst-Bruinsma IE. Sex and gender differences in axial spondyloarthritis: myths and truths. Rheumatology. 2020;59:iv38-46. DOI:10.1093/rheumatology/keaa543.
  40. Ciurea A, Scherer A, Weber U, Exer P, Bernhard J, Tamborrini G, et al. Impaired response to treatment with tumour necrosis factor α inhibitors in smokers with axial spondyloarthritis. Ann Rheum Dis. 2016;75(3):532-539. DOI:10.1136/annrheumdis-2013-205133.
  41. Shukla A, Gaur P, Aggarwal A. Tenascin-C levels, a toll-like receptor 4 ligand, in enthesitis-related arthritis category of juvenile idiopathic arthritis: a cross-sectional and longitudinal study. J Rheumatol. 2015;42(5):891-896. DOI:10.3899/jrheum.141365.
  42. Riedl S, Tandara A, Reinshagen M, Hinz U, Faissner A, Bodenmüller H, et al. Serum tenascin-C is an indicator of inflammatory bowel disease activity. Int J Colorectal Dis. 2001;16(5):285-291. DOI:10.1007/s003840100312.
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.