Microparticles: potential new contributors to the pathogenesis of systemic sclerosis?

Advances in Rheumatology - Tập 63 - Trang 1-8 - 2023
Sandra Maximiano de Oliveira1, Ighor Luiz de Azevedo Teixeira2, Carolina Nunes França2,3, Maria Cristina de Oliveira Izar2, Cristiane Kayser1
1Rheumatology Division, Escola Paulista de Medicina, Federal University of São Paulo – UNIFESP, São Paulo, Brazil
2Laboratory of Cellular and Molecular Biology – Lipids, Atherosclerosis and Vascular Biology Section, Cardiology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo – UNIFESP, São Paulo, Brazil
3Postgraduate Program in Health Sciences, Universidade de Santo Amaro – UNISA, São Paulo, Brazil

Tóm tắt

Microparticles (MPs) are membrane-derived vesicles released from cells undergoing activation or apoptosis with diverse proinflammatory and prothrombotic activities, that have been implicated in the pathogenesis of systemic sclerosis (SSc). We aimed to evaluate the plasma levels of platelet-derived microparticles (PMPs), endothelial cell-derived microparticles (EMPs), and monocyte-derived microparticles (MMPs) in SSc patients, and the association between MPs and the clinical features of SSc. In this cross-sectional study, 70 patients with SSc and 35 age- and sex-matched healthy controls were evaluated. Clinical and nailfold capillaroscopy (NFC) data were obtained from all patients. Plasma levels of PMPs (CD42+/31+), EMPs (CD105+), and MMPs (CD14+) were quantified by flow cytometry. Patients were mainly females (90%), with a mean age of 48.9 years old. PMP, EMP, and MMP levels were significantly increased in SSc patients compared to controls (79.2% ± 17.3% vs. 71.0% ± 19.8%, p = 0.033; 43.5% ± 8.7% vs. 37.8% ± 10.4%, p = 0.004; and 3.5% ± 1.3% vs. 1.1% ± 0.5%, p < 0.0001, respectively). PMP levels were significantly higher in patients with positive anti-topoisomerase-I antibodies (p = 0.030) and in patients with a disease duration > 3 years (p = 0.038). EMP levels were lower in patients with a higher modified Rodnan skin score (p = 0.015), and in those with an avascular score > 1.5 in NFC (p = 0.042). The increased levels of PMPs, EMPs and MMPs in scleroderma patients might indicate a possible role for these agents in the pathogenesis of this challenging disease.

Tài liệu tham khảo

Allanore Y, Simms R, Distler O, et al. Systemic sclerosis. Nat Rev Dis Primers. 2015;1:15002. https://doi.org/10.1038/nrdp.2015.2. Saketkoo LA, Frech T, Varjú C, et al. A comprehensive framework for navigating patient care in systemic sclerosis: a global response to the need for improving the practice of diagnostic and preventive strategies in SSc. Best Pract Res Clin Rheumatol. 2021;35(3):101707. https://doi.org/10.1016/j.berh.2021.101707. Cutolo M, Soldano S, Smith V. Pathophysiology of systemic sclerosis: current understanding and new insights. Expert Rev Clin Immunol. 2019;15(7):753–64. https://doi.org/10.1080/1744666X.2019.1614915. Ntelis K, Solomou EE, Sakkas L, Stamatis-Nick L, Daoussis D. The role of platelets in autoimmunity, vasculopathy, and fibrosis: Implications for systemic sclerosis. Semin Arthritis Rheum. 2017;47(3):409–17. https://doi.org/10.1016/j.semarthrit.2017.05.004. Pauling JD, O’Donnell VB, Mchugh NJ. The contribution of platelets to the pathogenesis of Raynaud’s phenomenon and systemic sclerosis. Platelets. 2013;24(7):503–15. https://doi.org/10.3109/09537104.2012.719090. Pisetsky DS, Ullal AJ, Gauley J, Ning TC. Microparticles as mediators and biomarkers of rheumatic disease. Rheumatology (Oxford). 2012;51(10):1737–46. https://doi.org/10.1093/rheumatology/kes028. Ratajczak MZ, Ratajczak J. Extracellular microvesicles/exosomes: discovery, disbelief, acceptance, and the future? Leukemia. 2020;34(12):3126–35. https://doi.org/10.1038/s41375-020-01041-z. Morel O, Morel N, Freyssinet JM, Toti F. Platelet microparticles and vascular cells interactions: a checkpoint between the haemostatic and thrombotic responses. Platelets. 2008;19(1):9–23. https://doi.org/10.1080/09537100701817232. Čolić J, Matucci-Cerinic M, Guiducci S, Damjanov N. Microparticles in systemic sclerosis, targets or tools to control fibrosis: this is the question! J Scleroderma Relat Disord. 2020;5(1):6–20. https://doi.org/10.1177/2397198319857356. Roos MA, Gennero L, Denysenko T, et al. Microparticles in physiological and in pathological conditions. Cell Biochem Funct. 2010;28(7):539–48. https://doi.org/10.1002/cbf.1695. Beyer C, Pisetsky DS. The role of microparticles in the pathogenesis of rheumatic diseases. Nat Rev Rheumatol. 2010;6(1):21–9. https://doi.org/10.1038/nrrheum.2009.229. McCarthy EM, Moreno-Martinez D, Wilkinson FL, et al. Microparticle subpopulations are potential markers of disease progression and vascular dysfunction across a spectrum of connective tissue disease. BBA Clin. 2016;7:16–22. https://doi.org/10.1016/j.bbacli.2016.11.003. Guiducci S, Distler JH, Jüngel A, et al. The relationship between plasma microparticles and disease manifestations in patients with systemic sclerosis. Arthritis Rheum. 2008;58(9):2845–53. https://doi.org/10.1002/art.23735. Nomura S, Inami N, Ozaki Y, Kagawa H, Fukuhara S. Significance of microparticles in progressive systemic sclerosis with interstitial pneumonia. Platelets. 2008;19(3):192–8. https://doi.org/10.1080/09537100701882038. Maugeri N, Franchini S, Campana L, et al. Circulating platelets as a source of the damage-associated molecular pattern HMGB1 in patients with systemic sclerosis. Autoimmunity. 2012;45(8):584–7. https://doi.org/10.3109/08916934.2012.719946. Michalska-Jakubus M, Kowal-Bielecka O, Smith V, Cutolo M, Krasowska D. Plasma endothelial microparticles reflect the extent of capillaroscopic alterations and correlate with the severity of skin involvement in systemic sclerosis. Microvasc Res. 2017;110:24–31. https://doi.org/10.1016/j.mvr.2016.11.006. Iversen LV, Østergaard O, Ullman S, et al. Circulating microparticles and plasma levels of soluble E- and P-selectins in patients with systemic sclerosis. Scand J Rheumatol. 2013;42(6):473–82. https://doi.org/10.3109/03009742.2013.796403. Iversen LV, Ullman S, Østergaard O, et al. Cross-sectional study of soluble selectins, fractions of circulating microparticles and their relationship to lung and skin involvement in systemic sclerosis. BMC Musculoskelet Disord. 2015;16:191. https://doi.org/10.1186/s12891-015-0653-8. Scanu A, Molnarfi N, Brandt KJ, Gruaz L, Dayer JM, Burger D. Stimulated T cells generate microparticles, which mimic cellular contact activation of human monocytes: differential regulation of pro- and anti-inflammatory cytokine production by high-density lipoproteins. J Leukoc Biol. 2008;83(4):921–7. https://doi.org/10.1189/jlb.0807551. Kania G, Rudnik M, Distler O. Involvement of the myeloid cell compartment in fibrogenesis and systemic sclerosis. Nat Rev Rheumatol. 2019;15(5):288–302. https://doi.org/10.1038/s41584-019-0212-z. van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2013;72(11):1747–55. https://doi.org/10.1136/annrheumdis-2013-204424. Humbert M, Kovacs G, Hoeper MM, et al. ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2022;2022:2200879. https://doi.org/10.1183/13993003.00879-2022. Denton CP, Lapadula G, Mouthon L, Müller-Ladner U. Renal complications and scleroderma renal crisis. Rheumatology (Oxford). 2009;48(Suppl 3):iii32–5. https://doi.org/10.1093/rheumatology/ken483. Clements P, Lachenbruch P, Siebold J, et al. Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis. J Rheumatol. 1995;22(7):1281–5. Sekiyama JY, Camargo CZ, Eduardo L, Andrade C, Kayser C. Reliability of widefield nailfold capillaroscopy and video capillaroscopy in the assessment of patients with Raynaud’s phenomenon. Arthritis Care Res (Hoboken). 2013;65(11):1853–61. https://doi.org/10.1002/acr.22054. Cutolo M, Sulli A, Pizzorni C, Accardo S. Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis. J Rheumatol. 2000;27(1):155–60. Fonseca F, Ballerini AP, Izar MC, et al. Advanced chronic kidney disease is associated with higher serum concentration of monocyte microparticles. Life Sci. 2020;260:118295. https://doi.org/10.1016/j.lfs.2020.118295. Dunne JV, Bankole J, Keen KJ. Systematic review of the role of microparticles in systemic sclerosis. Curr Rheumatol Rev. 2013;9(4):279–300. https://doi.org/10.2174/1573397109666140103001139. Denton CP, Black CM, Abraham DJ. Mechanisms and consequences of fibrosis in systemic sclerosis. Nat Clin Pract Rheumatol. 2006;2(3):134–44. https://doi.org/10.1038/ncprheum0115. Guilpain P, Noël D, Avouac J. Editorial: key players in systemic sclerosis: the immune system and beyond. Front Immunol. 2021;12:770419. https://doi.org/10.3389/fimmu.2021.770419. Kayser C, Fritzler MJ. Autoantibodies in systemic sclerosis: unanswered questions. Front Immunol. 2015;6:167. https://doi.org/10.3389/fimmu.2015.00167. Ho KT, Reveille JD. The clinical relevance of autoantibodies in scleroderma. Arthritis Res Ther. 2003;5(2):80–93. https://doi.org/10.1186/ar628. Boonstra M, Bakker JA, Grummels A, et al. Association of anti-topoisomerase I antibodies of the IgM isotype with disease progression in anti-topoisomerase i-positive systemic sclerosis. Arthritis Rheumatol. 2020;72(11):1897–904. https://doi.org/10.1002/art.41403. Leleu D, Levionnois E, Laurent P, Lazaro E, Richez C, Duffau P, et al. Elevated circulatory levels of microparticles are associated to lung fibrosis and vasculopathy during systemic sclerosis. Front Immunol. 2020;11:532177. Lammi MR, Saketkoo LA, Okpechi SC, et al. Microparticles in systemic sclerosis: potential pro-inflammatory mediators and pulmonary hypertension biomarkers. Respirology. 2019;24(7):675–83. https://doi.org/10.1111/resp.13500. Distler JH, Jüngel A, Huber LC, et al. The induction of matrix metalloproteinase and cytokine expression in synovial fibroblasts stimulated with immune cell microparticles. Proc Natl Acad Sci USA. 2005;102(8):2892–7. https://doi.org/10.1073/pnas.0409781102. Lambova SN, Müller-Ladner U. Nailfold capillaroscopy in systemic sclerosis – state of the art: the evolving knowledge about capillaroscopic abnormalities in systemic sclerosis. J Scleroderma Relat Disord. 2019;4(3):200–11. https://doi.org/10.1177/2397198319833486. Markusse IM, Meijs J, de Boer B, et al. Predicting cardiopulmonary involvement in patients with systemic sclerosis: complementary value of nailfold videocapillaroscopy patterns and disease-specific autoantibodies. Rheumatology (Oxford). 2017;56(7):1081–8. https://doi.org/10.1093/rheumatology/kew402. Kayser C, Sekiyama JY, Próspero LC, Camargo CZ, Andrade LE. Nailfold capillaroscopy abnormalities as predictors of mortality in patients with systemic sclerosis. Clin Exp Rheumatol. 2013;31(2 Suppl 76):103–8. Tura-Ceide O, Blanco I, Garcia-Lucio J, et al. Circulating cell biomarkers in pulmonary arterial hypertension: relationship with clinical heterogeneity and therapeutic response. Cells. 2021;10(7):1688. https://doi.org/10.3390/cells10071688. Tourkina E, Bonner M, Oates J, et al. Altered monocyte and fibrocyte phenotype and function in scleroderma interstitial lung disease: reversal by caveolin-1 scaffolding domain peptide. Fibrogenesis Tissue Repair. 2011;4(1):15. https://doi.org/10.1186/1755-1536-4-15.