Microparticles: potential new contributors to the pathogenesis of systemic sclerosis?
Capillaroscopy
Microangiopathy
Microparticles
Systemic sclerosis
Journal
Advances in rheumatology (London, England)
ISSN: 2523-3106
Titre abrégé: Adv Rheumatol
Pays: England
ID NLM: 101734172
Informations de publication
Date de publication:
25 04 2023
25 04 2023
Historique:
received:
05
11
2022
accepted:
12
04
2023
medline:
27
4
2023
pubmed:
26
4
2023
entrez:
25
4
2023
Statut:
epublish
Résumé
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 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.
Sections du résumé
BACKGROUND
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.
METHODS
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
RESULTS
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).
CONCLUSION
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.
Identifiants
pubmed: 37098600
doi: 10.1186/s42358-023-00299-y
pii: 10.1186/s42358-023-00299-y
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
19Informations de copyright
© 2023. The Author(s).
Références
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 .
doi: 10.1038/nrdp.2015.2
pubmed: 27189141
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 .
doi: 10.1016/j.berh.2021.101707
pubmed: 34538573
pmcid: 8670736
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 .
doi: 10.1080/1744666X.2019.1614915
pubmed: 31046487
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 .
doi: 10.1016/j.semarthrit.2017.05.004
pubmed: 28602360
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 .
doi: 10.3109/09537104.2012.719090
pubmed: 22966961
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 .
doi: 10.1093/rheumatology/kes028
pubmed: 22403183
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 .
doi: 10.1038/s41375-020-01041-z
pubmed: 32929129
pmcid: 7685969
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 .
doi: 10.1080/09537100701817232
pubmed: 18231934
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 .
doi: 10.1177/2397198319857356
pubmed: 35382401
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 .
doi: 10.1002/cbf.1695
pubmed: 20941744
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 .
doi: 10.1038/nrrheum.2009.229
pubmed: 19949432
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 .
doi: 10.1016/j.bbacli.2016.11.003
pubmed: 28053878
pmcid: 5199156
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 .
doi: 10.1002/art.23735
pubmed: 18759303
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 .
doi: 10.1080/09537100701882038
pubmed: 18432520
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 .
doi: 10.3109/08916934.2012.719946
pubmed: 22928592
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 .
doi: 10.1016/j.mvr.2016.11.006
pubmed: 27889559
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 .
doi: 10.3109/03009742.2013.796403
pubmed: 24016306
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 .
doi: 10.1186/s12891-015-0653-8
pubmed: 26265409
pmcid: 4534013
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 .
doi: 10.1189/jlb.0807551
pubmed: 18223103
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 .
doi: 10.1038/s41584-019-0212-z
pubmed: 30953037
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 .
doi: 10.1136/annrheumdis-2013-204424
pubmed: 24092682
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 .
doi: 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 .
doi: 10.1093/rheumatology/ken483
pubmed: 19487221
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.
pubmed: 7562759
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 .
doi: 10.1002/acr.22054
pubmed: 23754794
Cutolo M, Sulli A, Pizzorni C, Accardo S. Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis. J Rheumatol. 2000;27(1):155–60.
pubmed: 10648032
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 .
doi: 10.1016/j.lfs.2020.118295
pubmed: 32822720
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 .
doi: 10.2174/1573397109666140103001139
pubmed: 26932294
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 .
doi: 10.1038/ncprheum0115
pubmed: 16932673
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 .
doi: 10.3389/fimmu.2021.770419
pubmed: 34659272
pmcid: 8514991
Kayser C, Fritzler MJ. Autoantibodies in systemic sclerosis: unanswered questions. Front Immunol. 2015;6:167. https://doi.org/10.3389/fimmu.2015.00167 .
doi: 10.3389/fimmu.2015.00167
pubmed: 25926833
pmcid: 4397862
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 .
doi: 10.1186/ar628
pubmed: 12718748
pmcid: 2833871
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 .
doi: 10.1002/art.41403
pubmed: 32840062
pmcid: 7702063
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.
doi: 10.3389/fimmu.2020.532177
pubmed: 33193304
pmcid: 7645042
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 .
doi: 10.1111/resp.13500
pubmed: 30747487
pmcid: 6579687
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 .
doi: 10.1073/pnas.0409781102
pubmed: 15701693
pmcid: 548330
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 .
doi: 10.1177/2397198319833486
pubmed: 35382505
pmcid: 8922564
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 .
doi: 10.1093/rheumatology/kew402
pubmed: 27940596
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.
pubmed: 23324736
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 .
doi: 10.3390/cells10071688
pubmed: 34359858
pmcid: 8304946
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 .
doi: 10.1186/1755-1536-4-15
pubmed: 21722364
pmcid: 3155832