Salivary Levels of Interleukin-17 in Iranian Patients With Systemic Sclerosis
-
Ali Tadayon
,
Javad Moayedi
,
Mohamad Ali Nazarinia
,
Mahyar Malekzadeh
,
Sara Kazemi
,
Maryam Mardani
Abstract
Systemic sclerosis (SSc) is a rare immune-mediated rheumatic disease in which the skin, muscles, blood vessels, and internal organs are damaged through chronic inflammation. Interleukin-17 (IL-17) is a potent pro-inflammatory cytokine produced by T helper 17 (Th17) cells, and plays a critical role in many inflammatory conditions. This study aims to assess the salivary IL-17 levels in Iranian patients with SSc. In this cross-sectional study, unstimulated saliva samples were collected from patients with SSc (n=80) and age- and sex- matched healthy individuals (n=80). The salivary levels of IL-17 in all samples were measured using a commercially available enzyme–linked immunosorbent assay (ELISA) kit. The mean salivary levels of IL-17 in patients with SSc were significantly higher than the control group (199.6±38.9 pg/mL vs. 112.7±39.4 pg/mL, P<0.0001). IL-17 in the patient group had a significant positive correlation with anticentromere antibody (ACA) concentration (r=0.875, P<0.0001). The salivary levels of IL-17 showed no significant differences between males and females. Based on the results, salivary levels of IL-17 could be considered a good marker to differentiate patients with SSc from healthy subjects. Considering the role of this inflammatory cytokine in tissue inflammation and its association with ACA concentration, IL-17 might be involved in the pathogenesis of SSc; however, further comprehensive studies are needed to confirm our findings.
1. Kurasawa K, Hirose K, Sano H, Endo H, Shinkai H, Nawata Y, et al. Increased interleukin‐17 production in patients with systemic sclerosis. Arthritis Rheum. 2000;43(11):2455-63.
2. Hashempour A, Moayedi J, Musavi Z, Ghasabi F, Halaji M, Hasanshahi Z, et al. First report of HHV-8 viral load and seroprevalence of major blood-borne viruses in Iranian patients with systemic sclerosis. Mult Scler Relat Disord. 2021;51(2021):102872.
3. Stern EP, Denton CP. The pathogenesis of systemic sclerosis. Rheum Dis Clin. 2015;41(3):367-82.
4. Yang X, Yang J, Xing X, Wan L, Li M. Increased frequency of Th17 cells in systemic sclerosis is related to disease activity and collagen overproduction. Arthritis Res Ther. 2014;16(1):1-11.
5. Fuschiotti P. Current perspectives on the immunopathogenesis of systemic sclerosis. Immunotargets Ther. 2016;5(1):21-35.
6. Singh N, Baby D, Rajguru JP, Patil PB, Thakkannavar SS, Pujari VB. Inflammation and cancer. Ann Afr Med. 2019;18(3):121-6.
7. Wu B, Sodji QH, Oyelere AK. Inflammation, fibrosis and cancer: Mechanisms, therapeutic options and challenges. Cancers. 2022;14(3):552-89.
8. Sierra-Sepúlveda A, Esquinca-González A, Benavides-Suárez SA, Sordo-Lima DE, Caballero-Islas AE, Cabral-Castañeda AR, et al. Systemic sclerosis pathogenesis and emerging therapies, beyond the fibroblast. Biomed Res Int. 2019;2019(4569826):1-15.
9. Qu N, Xu M, Mizoguchi I, Furusawa J-i, Kaneko K, Watanabe K, et al. Pivotal roles of T-helper 17-related cytokines, IL-17, IL-22, and IL-23, in inflammatory diseases. Clin Dev Immunol. 2013;2013(968549):1-13.
10. O’Reilly S, Hügle T, Van Laar JM. T cells in systemic sclerosis: a reappraisal. Rheumatology. 2012;51(9):1540-9.
11. Xu S, Cao X. Interleukin-17 and its expanding biological functions. Cell Mol Immunol. 2010;7(3):164-74.
12. Park SJ, Lee YC. Interleukin-17 regulation: an attractive therapeutic approach for asthma. Respir Res. 2010;11(1):1-11.
13. Tabarkiewicz J, Pogoda K, Karczmarczyk A, Pozarowski P, Giannopoulos K. The role of IL-17 and Th17 lymphocytes in autoimmune diseases. Arch Immunol Ther Exp. 2015;63(6):435-49.
14. Martin DA, Towne JE, Kricorian G, Klekotka P, Gudjonsson JE, Krueger JG, et al. The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings. J Invest Dermatol. 2013;133(1):17-26.
15. de Morales JMGR, Puig L, Daudén E, Cañete JD, Pablos JL, Martín AO, et al. Critical role of interleukin (IL)-17 in inflammatory and immune disorders: an updated review of the evidence focusing in controversies. Autoimmun Rev. 2020;19(1):102429.
16. Liu Y, HO RCM, Mak A. The role of interleukin (IL)‐17 in anxiety and depression of patients with rheumatoid arthritis. Int J Rheum Dis. 2012;15(2):183-7.
17. Rosu A, Margaritescu C, Stepan A, Musetescu A, Ene M. IL-17 patterns in synovium, serum and synovial fluid from treatment-naive, early rheumatoid arthritis patients. Rom J Morphol Embryol. 2012;53(1):73-80.
18. Bilik MZ, Kaplan I, Polat N, Akil MA, Akyüz A, Acet H, et al. Serum levels of IL-17 and IL-23 in patients with rheumatic mitral stenosis. Medicine. 2016;95(18):e3562.
19. Chen XQ, Yu YC, Deng HH, Sun JZ, Dai Z, Wu YW, et al. Plasma IL-17A is increased in new-onset SLE patients and associated with disease activity. J Clin Immunol. 2010;30(2):221-5.
20. Katsifis GE, Rekka S, Moutsopoulos NM, Pillemer S, Wahl SM. Systemic and local interleukin-17 and linked cytokines associated with Sjögren’s syndrome immunopathogenesis. Am J Pathol. 2009;175(3):1167-77.
21. Esendagli G, Kurne AT, Sayat G, Kilic AK, Guc D, Karabudak R. Evaluation of Th17-related cytokines and receptors in multiple sclerosis patients under interferon beta-1 therapy. J Neuroimmunol. 2013;255(1-2):81-4.
22. Bălaşa R, Bajko Z, Huţanu A. Serum levels of IL-17A in patients with relapsing–remitting multiple sclerosis treated with interferon-β. Mult Scler J. 2013;19(7):885-90.
23. Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut. 2003;52(1):65-70.
24. Nielsen O, Kirman I, Rüdiger N, Hendel J, Vainer B. Upregulation of interleukin-12 and-17 in active inflammatory bowel disease. Scand J Gastroenterol. 2003;38(2):180-5.
25. Coimbra S, Oliveira H, Reis F, Belo L, Rocha S, Quintanilha A, et al. Interleukin (IL)‐22, IL‐17, IL‐23, IL‐8, vascular endothelial growth factor and tumour necrosis factor‐α levels in patients with psoriasis before, during and after psoralen–ultraviolet A and narrowband ultraviolet B therapy. Br J Dermatol. 2010;163(6):1282-90.
26. Ivanov S, Lindén A. Interleukin-17 as a drug target in human disease. Trends Pharmacol Sci. 2009;30(2):95-103.
27. Najafi S, Mardani M, Motamedifar M, Nazarinia MA, Hadadi M. Salivary Streptococcus mutans and Lactobacilli Levels as Indicators of Dental Caries Development in Iranian Patients with Systemic Sclerosis. Iran J Med Microbiol. 2022;16(4):350-6.
28. Parat K, Radić M, Perković D, Lukenda DB, Kaliterna DM. Reduced salivary flow and caries status are correlated with disease activity and severity in patients with diffuse cutaneous systemic sclerosis. J Int Med Res. 2020;48(10):0300060520941375.
29. Abbas MJ, Al Rawi NA, Al-Duboni GI. The role of salivary interleukin 17 as a dependent positive predictive biomarker among iraqi patients with oral squamous cell carcinoma. J Pharm Sci Res. 2018;10(12):3149-52.
30. Saheb Sharif-Askari F, Sharif-Askari NS, Hafezi S, Mdkhana B, Alsayed HAH, Ansari AW, et al. Interleukin-17, a salivary biomarker for COVID-19 severity. PloS One. 2022;17(9):e0274841.
31. Verstappen GM, Corneth OB, Bootsma H, Kroese FG. Th17 cells in primary Sjögren's syndrome: pathogenicity and plasticity. J Autoimmun. 2018;87:16-25.
32. Asano Y. The pathogenesis of systemic sclerosis: An understanding based on a common pathologic cascade across multiple organs and additional organ-specific pathologies. J Clin Med. 2020;9(9):2687-714.
33. Robak E, Gerlicz-Kowalczuk Z, Dziankowska-Bartkowiak B, Wozniacka A, Bogaczewicz J. Serum concentrations of IL-17A, IL-17B, IL-17E and IL-17F in patients with systemic sclerosis. Arch Med Sci. 2019;15(3):706-12.
34. Murata M, Fujimoto M, Matsushita T, Hamaguchi Y, Hasegawa M, Takehara K, et al. Clinical association of serum interleukin-17 levels in systemic sclerosis: is systemic sclerosis a Th17 disease? J Dermatol Sci. 2008;50(3):240-2.
35. Dantas AT, de Almeida AR, Sampaio MCPD, Cordeiro MF, de Oliveira PSS, de Ataíde Mariz H, et al. Different profile of cytokine production in patients with systemic sclerosis and association with clinical manifestations. Immunol Lett. 2018;198(1):12-6.
36. Rolla G, Fusaro E, Nicola S, Bucca C, Peroni C, Parisi S, et al. Th-17 cytokines and interstitial lung involvement in systemic sclerosis. J Breath Res. 2016;10(4):046013.
37. Chizzolini C, Dufour AM, Brembilla NC. Is there a role for IL-17 in the pathogenesis of systemic sclerosis? Immunol Lett. 2018;195(1):61-7.
38. Zhang LW, Zhou PR, Wei P, Cong X, Wu LL, Hua H. Expression of interleukin‐17 in primary Sjögren's syndrome and the correlation with disease severity: A systematic review and meta‐analysis. Scand J Immunol. 2018;87(4):e12649.
39. Voigt A, Esfandiary L, Wanchoo A, Glenton P, Donate A, Craft WF, et al. Sexual dimorphic function of IL-17 in salivary gland dysfunction of the C57BL/6. NOD-Aec1Aec2 model of Sjögren’s syndrome. Sci Rep. 2016;6(1):1-14.
40. Zian Z, Bakkach J, Barakat A, Ghailani Nourouti N, Bennani Mechita M. Salivary biomarkers in systemic sclerosis disease. Biomed Res Int. 2018;2018(2018):1-7.
41. Abdeldayem E, Rashed L, Ali S. Salivary expression of lncRNA DQ786243 and IL-17 in oral lichen planus: case–control study. BMC Oral Health. 2022;22(1):1-7.
42. El-Refai I, Maged A, El-Saady D. Assessment of IL-17 in Oral Lichen Planus and in Pemphigus Vulgaris. Egypt Dent J. 2019;65(1):343-50.
43. Wojeck RK, Bailey DE, Somers TJ, Knisely MR. Self‐management interventions in systemic sclerosis: A systematic review. Res Nurs Health. 2021;44(2):376-92.
44. Sherby NA, Sediq AM, Alsharawy AAO, Hammad MAH. Quality Of Life in Female Patients with Systemic Sclerosis. Egypt J Hosp Med. 2022;87(1):1208-15.
45. Țiburcă L, Bembea M, Zaha DC, Jurca AD, Vesa CM, Rațiu IA, et al. The Treatment with Interleukin 17 Inhibitors and Immune-Mediated Inflammatory Diseases. Curr Issues Mol Biol. 2022;44(5):1851-66.
46. Gao Q, Zhao Y, Wang X, Shi J, Wang H. Efficacy and safety of IL-17 inhibitors for patients with psoriatic arthritis: A systematic review and meta-analysis. Eur Rev Med Pharmacol Sci. 2021;25(1):2958-70.
2. Hashempour A, Moayedi J, Musavi Z, Ghasabi F, Halaji M, Hasanshahi Z, et al. First report of HHV-8 viral load and seroprevalence of major blood-borne viruses in Iranian patients with systemic sclerosis. Mult Scler Relat Disord. 2021;51(2021):102872.
3. Stern EP, Denton CP. The pathogenesis of systemic sclerosis. Rheum Dis Clin. 2015;41(3):367-82.
4. Yang X, Yang J, Xing X, Wan L, Li M. Increased frequency of Th17 cells in systemic sclerosis is related to disease activity and collagen overproduction. Arthritis Res Ther. 2014;16(1):1-11.
5. Fuschiotti P. Current perspectives on the immunopathogenesis of systemic sclerosis. Immunotargets Ther. 2016;5(1):21-35.
6. Singh N, Baby D, Rajguru JP, Patil PB, Thakkannavar SS, Pujari VB. Inflammation and cancer. Ann Afr Med. 2019;18(3):121-6.
7. Wu B, Sodji QH, Oyelere AK. Inflammation, fibrosis and cancer: Mechanisms, therapeutic options and challenges. Cancers. 2022;14(3):552-89.
8. Sierra-Sepúlveda A, Esquinca-González A, Benavides-Suárez SA, Sordo-Lima DE, Caballero-Islas AE, Cabral-Castañeda AR, et al. Systemic sclerosis pathogenesis and emerging therapies, beyond the fibroblast. Biomed Res Int. 2019;2019(4569826):1-15.
9. Qu N, Xu M, Mizoguchi I, Furusawa J-i, Kaneko K, Watanabe K, et al. Pivotal roles of T-helper 17-related cytokines, IL-17, IL-22, and IL-23, in inflammatory diseases. Clin Dev Immunol. 2013;2013(968549):1-13.
10. O’Reilly S, Hügle T, Van Laar JM. T cells in systemic sclerosis: a reappraisal. Rheumatology. 2012;51(9):1540-9.
11. Xu S, Cao X. Interleukin-17 and its expanding biological functions. Cell Mol Immunol. 2010;7(3):164-74.
12. Park SJ, Lee YC. Interleukin-17 regulation: an attractive therapeutic approach for asthma. Respir Res. 2010;11(1):1-11.
13. Tabarkiewicz J, Pogoda K, Karczmarczyk A, Pozarowski P, Giannopoulos K. The role of IL-17 and Th17 lymphocytes in autoimmune diseases. Arch Immunol Ther Exp. 2015;63(6):435-49.
14. Martin DA, Towne JE, Kricorian G, Klekotka P, Gudjonsson JE, Krueger JG, et al. The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings. J Invest Dermatol. 2013;133(1):17-26.
15. de Morales JMGR, Puig L, Daudén E, Cañete JD, Pablos JL, Martín AO, et al. Critical role of interleukin (IL)-17 in inflammatory and immune disorders: an updated review of the evidence focusing in controversies. Autoimmun Rev. 2020;19(1):102429.
16. Liu Y, HO RCM, Mak A. The role of interleukin (IL)‐17 in anxiety and depression of patients with rheumatoid arthritis. Int J Rheum Dis. 2012;15(2):183-7.
17. Rosu A, Margaritescu C, Stepan A, Musetescu A, Ene M. IL-17 patterns in synovium, serum and synovial fluid from treatment-naive, early rheumatoid arthritis patients. Rom J Morphol Embryol. 2012;53(1):73-80.
18. Bilik MZ, Kaplan I, Polat N, Akil MA, Akyüz A, Acet H, et al. Serum levels of IL-17 and IL-23 in patients with rheumatic mitral stenosis. Medicine. 2016;95(18):e3562.
19. Chen XQ, Yu YC, Deng HH, Sun JZ, Dai Z, Wu YW, et al. Plasma IL-17A is increased in new-onset SLE patients and associated with disease activity. J Clin Immunol. 2010;30(2):221-5.
20. Katsifis GE, Rekka S, Moutsopoulos NM, Pillemer S, Wahl SM. Systemic and local interleukin-17 and linked cytokines associated with Sjögren’s syndrome immunopathogenesis. Am J Pathol. 2009;175(3):1167-77.
21. Esendagli G, Kurne AT, Sayat G, Kilic AK, Guc D, Karabudak R. Evaluation of Th17-related cytokines and receptors in multiple sclerosis patients under interferon beta-1 therapy. J Neuroimmunol. 2013;255(1-2):81-4.
22. Bălaşa R, Bajko Z, Huţanu A. Serum levels of IL-17A in patients with relapsing–remitting multiple sclerosis treated with interferon-β. Mult Scler J. 2013;19(7):885-90.
23. Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut. 2003;52(1):65-70.
24. Nielsen O, Kirman I, Rüdiger N, Hendel J, Vainer B. Upregulation of interleukin-12 and-17 in active inflammatory bowel disease. Scand J Gastroenterol. 2003;38(2):180-5.
25. Coimbra S, Oliveira H, Reis F, Belo L, Rocha S, Quintanilha A, et al. Interleukin (IL)‐22, IL‐17, IL‐23, IL‐8, vascular endothelial growth factor and tumour necrosis factor‐α levels in patients with psoriasis before, during and after psoralen–ultraviolet A and narrowband ultraviolet B therapy. Br J Dermatol. 2010;163(6):1282-90.
26. Ivanov S, Lindén A. Interleukin-17 as a drug target in human disease. Trends Pharmacol Sci. 2009;30(2):95-103.
27. Najafi S, Mardani M, Motamedifar M, Nazarinia MA, Hadadi M. Salivary Streptococcus mutans and Lactobacilli Levels as Indicators of Dental Caries Development in Iranian Patients with Systemic Sclerosis. Iran J Med Microbiol. 2022;16(4):350-6.
28. Parat K, Radić M, Perković D, Lukenda DB, Kaliterna DM. Reduced salivary flow and caries status are correlated with disease activity and severity in patients with diffuse cutaneous systemic sclerosis. J Int Med Res. 2020;48(10):0300060520941375.
29. Abbas MJ, Al Rawi NA, Al-Duboni GI. The role of salivary interleukin 17 as a dependent positive predictive biomarker among iraqi patients with oral squamous cell carcinoma. J Pharm Sci Res. 2018;10(12):3149-52.
30. Saheb Sharif-Askari F, Sharif-Askari NS, Hafezi S, Mdkhana B, Alsayed HAH, Ansari AW, et al. Interleukin-17, a salivary biomarker for COVID-19 severity. PloS One. 2022;17(9):e0274841.
31. Verstappen GM, Corneth OB, Bootsma H, Kroese FG. Th17 cells in primary Sjögren's syndrome: pathogenicity and plasticity. J Autoimmun. 2018;87:16-25.
32. Asano Y. The pathogenesis of systemic sclerosis: An understanding based on a common pathologic cascade across multiple organs and additional organ-specific pathologies. J Clin Med. 2020;9(9):2687-714.
33. Robak E, Gerlicz-Kowalczuk Z, Dziankowska-Bartkowiak B, Wozniacka A, Bogaczewicz J. Serum concentrations of IL-17A, IL-17B, IL-17E and IL-17F in patients with systemic sclerosis. Arch Med Sci. 2019;15(3):706-12.
34. Murata M, Fujimoto M, Matsushita T, Hamaguchi Y, Hasegawa M, Takehara K, et al. Clinical association of serum interleukin-17 levels in systemic sclerosis: is systemic sclerosis a Th17 disease? J Dermatol Sci. 2008;50(3):240-2.
35. Dantas AT, de Almeida AR, Sampaio MCPD, Cordeiro MF, de Oliveira PSS, de Ataíde Mariz H, et al. Different profile of cytokine production in patients with systemic sclerosis and association with clinical manifestations. Immunol Lett. 2018;198(1):12-6.
36. Rolla G, Fusaro E, Nicola S, Bucca C, Peroni C, Parisi S, et al. Th-17 cytokines and interstitial lung involvement in systemic sclerosis. J Breath Res. 2016;10(4):046013.
37. Chizzolini C, Dufour AM, Brembilla NC. Is there a role for IL-17 in the pathogenesis of systemic sclerosis? Immunol Lett. 2018;195(1):61-7.
38. Zhang LW, Zhou PR, Wei P, Cong X, Wu LL, Hua H. Expression of interleukin‐17 in primary Sjögren's syndrome and the correlation with disease severity: A systematic review and meta‐analysis. Scand J Immunol. 2018;87(4):e12649.
39. Voigt A, Esfandiary L, Wanchoo A, Glenton P, Donate A, Craft WF, et al. Sexual dimorphic function of IL-17 in salivary gland dysfunction of the C57BL/6. NOD-Aec1Aec2 model of Sjögren’s syndrome. Sci Rep. 2016;6(1):1-14.
40. Zian Z, Bakkach J, Barakat A, Ghailani Nourouti N, Bennani Mechita M. Salivary biomarkers in systemic sclerosis disease. Biomed Res Int. 2018;2018(2018):1-7.
41. Abdeldayem E, Rashed L, Ali S. Salivary expression of lncRNA DQ786243 and IL-17 in oral lichen planus: case–control study. BMC Oral Health. 2022;22(1):1-7.
42. El-Refai I, Maged A, El-Saady D. Assessment of IL-17 in Oral Lichen Planus and in Pemphigus Vulgaris. Egypt Dent J. 2019;65(1):343-50.
43. Wojeck RK, Bailey DE, Somers TJ, Knisely MR. Self‐management interventions in systemic sclerosis: A systematic review. Res Nurs Health. 2021;44(2):376-92.
44. Sherby NA, Sediq AM, Alsharawy AAO, Hammad MAH. Quality Of Life in Female Patients with Systemic Sclerosis. Egypt J Hosp Med. 2022;87(1):1208-15.
45. Țiburcă L, Bembea M, Zaha DC, Jurca AD, Vesa CM, Rațiu IA, et al. The Treatment with Interleukin 17 Inhibitors and Immune-Mediated Inflammatory Diseases. Curr Issues Mol Biol. 2022;44(5):1851-66.
46. Gao Q, Zhao Y, Wang X, Shi J, Wang H. Efficacy and safety of IL-17 inhibitors for patients with psoriatic arthritis: A systematic review and meta-analysis. Eur Rev Med Pharmacol Sci. 2021;25(1):2958-70.
| Files | ||
| Issue | Vol 62 No 4 (2024) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/acta.v62i4.17431 | |
| Keywords | ||
| Interleukin-17 (IL-17) Saliva Systemic sclerosis (SSc) | ||
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How to Cite
1.
Tadayon A, Moayedi J, Nazarinia MA, Malekzadeh M, Kazemi S, Mardani M. Salivary Levels of Interleukin-17 in Iranian Patients With Systemic Sclerosis. Acta Med Iran. 2024;62(4):182-187.
