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Serum-soluble ST2 and systemic sclerosis arthropathy

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Abstract

Interleukin (IL)33 and its receptor ST2 have been involved in the pathogenesis of several conditions, including arthritis. The aim of the study was to evaluate the association between IL33 or soluble ST2 (sST2) serum levels and systemic sclerosis (SSc) articular involvement. IL33 and sST2 serum levels were measured in 64 SSc patients and 24 HC matched for sex and age. Articular involvement assessed by using Disease Activity Score 28 based on erythrocyte sedimentation rate (DAS28-ESR), presence of tendon friction rubs (TFRs) and finger-to-palm (FTP) distance. sST2 serum levels were significantly higher in SSc patients with DAS28-ESR > 3.2 than in SSc patients with DAS28-ESR⩽3.2 [9726.1 (IQR 7746.5 – 14,953.5) pg/mL vs 7611.7 (IQR 5162.6 –11,036.7) pg/mL; p < 0.05]. sST2 serum levels were significantly higher in SSc patients with TFRs compared to SSc patients without TFRs [9726.1 (IQR 7746.5 – 14,953.5) pg/mL vs 7426.4 (IQR 5145.9 – 10,593.5) pg/mL; p < 0.01] and in SSc patients with FTP ≥ 1 cm compared to SSc patients with FTP < 1 cm [9683.7 (IQR 8067.2 – 16,387.6) pg/mL vs 7679.1 (IQR 5246.1 – 11,472.2) pg/mL; p < 0.05]. No significant association was observed between IL33 and DAS28-ESR, TFRs and FTP. A slightly positive linear correlation was found between sST2 and Disease Activity Index (r = 0.294, p < 0.05) and Disease Severity Scale (r = 0.265, p < 0.05). sST2 serum levels were positively correlated with DAS28-ESR (r = 0.371, p < 0.01). Elevated sST2 serum levels were associated with higher articular disease activity, TFRs and hand dysfunction, suggesting that sST2 might have a role in the pathogenesis of SSc articular involvement.

Key Points

• In SSc patients elevated serum levels of sST2 were associated with higher articular disease activity

• High serum levels of sST2 were reported in SSc patients with TFRs and hand dysfunction

• sST2 might have a role in the pathogenesis of SSc articular involvement

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References

  1. Avouac J, Clements PJ, Khanna D, Furst DE, Allanore Y (2012) Articular involvement in systemic sclerosis. Rheumatology (Oxford) 51:1347–1356. https://doi.org/10.1093/rheumatology/kes041

    Article  PubMed  Google Scholar 

  2. Sandler RD, Matucci-Cerinic M, Hughes M (2020) Musculoskeletal hand involvement in systemic sclerosis. Semin Arthritis Rheum 50:329–334. https://doi.org/10.1016/j.semarthrit.2019.11.003

    Article  PubMed  Google Scholar 

  3. van Leeuwen NM, Ciaffi J, Liem SIE, Huizinga TWJ, de Vries-Bouwstra JK (2021) Health-related quality of life in patients with systemic sclerosis: evolution over time and main determinants. Rheumatology (Oxford) 60:3646–3655. https://doi.org/10.1093/rheumatology/keaa827

    Article  PubMed  Google Scholar 

  4. Avouac J, Walker UA, Hachulla E et al (2016) Joint and tendon involvement predict disease progression in systemic sclerosis: a EUSTAR prospective study. Ann Rheum Dis 75:103–109. https://doi.org/10.1136/annrheumdis-2014-205295

    Article  PubMed  Google Scholar 

  5. Maurer B, Graf N, Michel BA et al (2015) Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the EUSTAR database. Ann Rheum Dis 74:1124–1131. https://doi.org/10.1136/annrheumdis-2014-205226

    Article  CAS  PubMed  Google Scholar 

  6. Wu W, Jordan S, Becker MO et al (2018) Prediction of progression of interstitial lung disease in patients with systemic sclerosis: the SPAR model. Ann Rheum Dis 77:1326–1332. https://doi.org/10.1136/annrheumdis-2018-213201

    Article  CAS  PubMed  Google Scholar 

  7. Lóránd V, Bálint Z, Komjáti D et al (2016) Validation of disease activity indices using the 28 joint counts in systemic sclerosis. Rheumatology (Oxford) 55:1849–1858. https://doi.org/10.1093/rheumatology/kew246

    Article  PubMed  Google Scholar 

  8. Lóránd V, Nagy G, Bálint Z et al (2021) Sensitivity to change of joint count composite indices in 72 patients with systemic sclerosis. Clin Exp Rheumatol 39(Suppl 131):77–84. https://doi.org/10.55563/clinexprheumatol/cl3bbb

    Article  PubMed  Google Scholar 

  9. Torok KS, Baker NA, Lucas M, Domsic RT, Boudreau R, Medsger TA Jr (2010) Reliability and validity of the delta finger-to-palm (FTP), a new measure of finger range of motion in systemic sclerosis. Clin Exp Rheumatol 28:S28–S36

    PubMed  PubMed Central  Google Scholar 

  10. Xu D, Barbour M, Jiang HR, Mu R (2019) Role of IL-33/ST2 signaling pathway in systemic sclerosis and other fibrotic diseases. Clin Exp Rheumatol 37(Suppl 119):141–146

    PubMed  Google Scholar 

  11. Kotsiou OS, Gourgoulianis KI, Zarogiannis SG (2018) IL-33/ST2 Axis in Organ Fibrosis. Front Immunol 9:2432. https://doi.org/10.3389/fimmu.2018.02432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Liu X, Xiao Y, Pan Y, Li H, Zheng SG, Su W (2019) The role of the IL-33/ST2 axis in autoimmune disorders: Friend or foe? Cytokine Growth Factor Rev 50:60–74. https://doi.org/10.1016/j.cytogfr.2019.04.004

    Article  CAS  PubMed  Google Scholar 

  13. Versace AG, Bitto A, Ioppolo C et al (2022) IL-13 and IL-33 Serum Levels Are Increased in Systemic Sclerosis Patients With Interstitial Lung Disease. Front Med (Lausanne) 9:825567. https://doi.org/10.3389/fmed.2022.825567

    Article  PubMed  Google Scholar 

  14. Li L, Zhu H, Zuo X (2018) Interleukin-33 in Systemic Sclerosis: Expression and Pathogenesis. Front Immunol 9:2663. https://doi.org/10.3389/fimmu.2018.02663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Xu D, Mu R, Wei X (2019) The Roles of IL-1 Family Cytokines in the Pathogenesis of Systemic Sclerosis. Front Immunol 10:2025. https://doi.org/10.3389/fimmu.2019.02025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Shi LJ, Liu C, Li JH, Zhu XY, Li YN, Li JT (2018) Elevated Levels of Soluble ST2 were Associated with Rheumatoid Arthritis Disease Activity and Ameliorated Inflammation in Synovial Fibroblasts. Chin Med J (Engl) 131:316–322. https://doi.org/10.4103/0366-6999.223847

    Article  CAS  PubMed  Google Scholar 

  17. Li XL, Lin TT, Qi CY et al (2013) Elevated serum level of IL-33 and sST2 in patients with ankylosing spondylitis: associated with disease activity and vascular endothelial growth factor. J Investig Med 61:848–851. https://doi.org/10.2310/jim.0b013e31828deed2

    Article  CAS  PubMed  Google Scholar 

  18. Ishikawa S, Shimizu M, Ueno K, Sugimoto N, Yachie A (2013) Soluble ST2 as a marker of disease activity in systemic juvenile idiopathic arthritis. Cytokine 62:272–277. https://doi.org/10.1016/j.cyto.2013.03.007

    Article  CAS  PubMed  Google Scholar 

  19. van den Hoogen F, Khanna D, Fransen J et al (2013) 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis 72:1747–1755. https://doi.org/10.1136/annrheumdis-2013-204424

    Article  PubMed  Google Scholar 

  20. LeRoy EC, Black C, Fleischmajer R et al (1988) Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 15:202–205

    CAS  PubMed  Google Scholar 

  21. Valentini G, Iudici M, Walker UA et al (2017) The European Scleroderma Trials and Research group (EUSTAR) task force for the development of revised activity criteria for systemic sclerosis: derivation and validation of a preliminarily revised EUSTAR activity index. Ann Rheum Dis 76:270–276. https://doi.org/10.1136/annrheumdis-2016-209768

    Article  CAS  PubMed  Google Scholar 

  22. Medsger TA Jr, Bombardieri S, Czirjak L, Scorza R, Della Rossa A, Bencivelli W (2003) Assessment of disease severity and prognosis. Clin Exp Rheumatol 21:S42–S46

    PubMed  Google Scholar 

  23. Steen VD, Medsger TA Jr (1997) The palpable tendon friction rub: an important physical examination finding in patients with systemic sclerosis. Arthritis Rheum 40:1146–1151. https://doi.org/10.1002/1529-0131(199706)40:6%3C1146::aid-art19%3E3.0.co;2-9

    Article  CAS  PubMed  Google Scholar 

  24. Prevoo ML, van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48. https://doi.org/10.1002/art.1780380107

    Article  CAS  PubMed  Google Scholar 

  25. Hong YS, Moon SJ, Joo YB et al (2011) Measurement of interleukin-33 (IL-33) and IL-33 receptors (sST2 and ST2L) in patients with rheumatoid arthritis. J Korean Med Sci 26:1132–1139. https://doi.org/10.3346/jkms.2011.26.9.1132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mok MY, Huang FP, Ip WK et al (2010) Serum levels of IL-33 and soluble ST2 and their association with disease activity in systemic lupus erythematosus. Rheumatology (Oxford) 49:520–527. https://doi.org/10.1093/rheumatology/kep402

    Article  CAS  PubMed  Google Scholar 

  27. Elhai M, Guerini H, Bazeli R et al (2012) Ultrasonographic hand features in systemic sclerosis and correlates with clinical, biologic, and radiographic findings. Arthritis Care Res (Hoboken) 64:1244–1249. https://doi.org/10.1002/acr.21668

    Article  PubMed  Google Scholar 

  28. Avouac J, Walker U, Tyndall A et al (2010) Characteristics of joint involvement and relationships with systemic inflammation in systemic sclerosis: results from the EULAR Scleroderma Trial and Research Group (EUSTAR) database. J Rheumatol 37:1488–1501. https://doi.org/10.3899/jrheum.091165

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell’Università 37, 00185, Rome, Italy

    Amalia Colalillo, Chiara Pellicano & Edoardo Rosato

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  1. Amalia Colalillo
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  2. Chiara Pellicano
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  3. Edoardo Rosato
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by all authors. The first draft of the manuscript was written by all authors, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Edoardo Rosato.

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Colalillo, A., Pellicano, C. & Rosato, E. Serum-soluble ST2 and systemic sclerosis arthropathy. Clin Rheumatol 42, 871–877 (2023). https://doi.org/10.1007/s10067-022-06367-w

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  • DOI: https://doi.org/10.1007/s10067-022-06367-w

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