{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T09:22:44Z","timestamp":1762075364106,"version":"build-2065373602"},"reference-count":63,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T00:00:00Z","timestamp":1667520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Systemic sclerosis (SSc, scleroderma) is a severe disease characterized by peripheral microcirculation abnormalities manifesting with Raynaud\u2019s phenomenon, nailfold videocapillaroscopic (NVC) changes, and even ischemic digital ulcers (DUs) that are often refractory to treatments. In the wake of previously described associations between the circulating levels of soluble junctional adhesion molecules (sJAMs) and SSc clinical features, here, we measured sJAM-A and sJAM-C levels by enzyme-linked immunosorbent assay in serum samples from a large case series of 110 SSc patients and 85 healthy controls, focusing on their possible association with peripheral vascular clinical features and their potential as biomarkers that are either diagnostic or mirror SSc-related microvasculopathy severity. Our data demonstrated that serum sJAM-A and sJAM-C are significantly increased in patients with SSc vs. healthy controls, especially in those featuring early\/active NVC patterns and the presence of ischemic DUs. Moreover, circulating sJAM-C levels showed good diagnostic accuracy in discriminating between patients and controls, as assessed by receiver operator characteristics curve analysis. Finally, logistic regression revealed that, when comparing sJAM-A to sJAM-C, the latter might be better suited as a biomarker for SSc-related DUs. Our promising findings provide the necessary groundwork for longitudinal follow-up analyses of SSc patients aiming to assess whether circulating sJAM-C levels might be predictive for the development of new DUs, as well as DU recurrence and\/or refractoriness to targeted therapies.<\/jats:p>","DOI":"10.3390\/life12111790","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T12:11:00Z","timestamp":1667909460000},"page":"1790","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Increased Circulating Soluble Junctional Adhesion Molecules in Systemic Sclerosis: Association with Peripheral Microvascular Impairment"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2744-8625","authenticated-orcid":false,"given":"Eloisa","family":"Romano","sequence":"first","affiliation":[{"name":"Section of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6352-0175","authenticated-orcid":false,"given":"Irene","family":"Rosa","sequence":"additional","affiliation":[{"name":"Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9275-7593","authenticated-orcid":false,"given":"Bianca Saveria","family":"Fioretto","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"},{"name":"Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Matucci-Cerinic","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"},{"name":"Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3956-8480","authenticated-orcid":false,"given":"Mirko","family":"Manetti","sequence":"additional","affiliation":[{"name":"Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/S0140-6736(17)30933-9","article-title":"Systemic sclerosis","volume":"390","author":"Denton","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"900638","DOI":"10.3389\/fimmu.2022.900638","article-title":"The pathophysiological roles of regulatory T cells in the early phase of systemic sclerosis","volume":"13","author":"Kobayashi","year":"2022","journal-title":"Front. 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