{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:22:03Z","timestamp":1768508523077,"version":"3.49.0"},"reference-count":58,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Serum C\u2013C motif chemokine ligand 18 (seCCL18) in systemic sclerosis (SSc) has been primarily associated with progressive interstitial lung disease (SSc-ILD) and mortality. However, its relationship with non-pulmonary organ involvement, disease activity, and long-term outcome has not been comprehensively evaluated. We therefore examined the clinical relevance of seCCL18 in a single-center SSc cohort. Methods: A total of 151 patients with SSc (83 diffuse cutaneous (dcSSc), 68 limited cutaneous SSc (lcSSc); median (IQR) disease duration: 9 (4;16) years) and 47 age- and sex-matched healthy controls (HCs) were enrolled. Serum CCL18 concentrations were measured by enzyme-linked immunosorbent assay. Elevated seCCL18 was defined as &gt;130 ng\/mL (mean + 2 SD of the healthy control group). Organ involvement and disease activity (EUSTAR Activity Index, EUSTAR-AI) were assessed at baseline, while survival was analysed longitudinally. Results: Patients with SSc had significantly higher seCCL18 levels than HCs (mean \u00b1 SD: 99.9 \u00b1 43.2 vs. 75.0 \u00b1 27.5 ng\/mL, p &lt; 0.01). Elevated seCCL18 was associated with SSc-ILD (81.1% vs. 60.5%, p = 0.022), reduced forced vital capacity (FVC &lt; 70%: 16.2% vs. 3.5%, p = 0.006), and reduced diffusing capacity for carbon monoxide (DLCO &lt; 70%: 80.6% vs. 54.4%, p = 0.005). Higher seCCL18 levels were observed in patients with myocardial disease (104.8 \u00b1 41.8 vs. 83.8 \u00b1 44.2 ng\/mL, p = 0.008), left ventricular diastolic dysfunction (107.1 \u00b1 40.5 vs. 84.5 \u00b1 45.0 ng\/mL, p &lt; 0.001), and oesophageal involvement (110.7 \u00b1 38.3 vs. 93.3 \u00b1 43.1 ng\/mL, p = 0.009). SeCCL18 levels above the cut-off were more frequently associated with tendon friction rubs (51.4% vs. 27.4%, p = 0.007), active disease (EUSTAR-AI \u2265 2.5: 73% vs. 44%, p = 0.002), and elevated inflammatory markers (CRP &gt; 5 mg\/L: 51.4% vs. 19.3%, p &lt; 0.001; ESR &gt; 28 mm\/h: 37.8% vs. 18.4%, p = 0.015). During a median follow-up of 87 months, 22 patients (15%) died. Elevated baseline seCCL18 predicted poorer survival in univariate analysis (log-rank p = 0.013) and remained an independent predictor of mortality in multivariable Cox regression (HR 1.789; 95% CI 1.133\u20132.824; p = 0.013), together with declining DLCO and reduced six-minute walk test performance. Conclusions: Elevated seCCL18 may identify patients with systemic sclerosis who exhibit a more severe multisystem phenotype, including cardiopulmonary, gastrointestinal, and musculoskeletal involvement, increased inflammatory activity, and reduced long-term survival. These findings suggest that seCCL18 may have some clinical utility as a prognostic biomarker reflecting widespread disease involvement beyond the lungs, even in patients with long-standing disease; however, the lack of an established cut-off value requires further validation in prospective, multicentre studies.<\/jats:p>","DOI":"10.3390\/biom16010136","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T08:17:32Z","timestamp":1768292252000},"page":"136","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum CCL18 May Reflect Multiorgan Involvement with Poor Outcome in Systemic Sclerosis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0223-1635","authenticated-orcid":false,"given":"Krist\u00f3f","family":"Filip\u00e1nits","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Medical School, University of P\u00e9cs, 7632 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7392-4114","authenticated-orcid":false,"given":"Gabriella","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Medical School, University of P\u00e9cs, 7632 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3700-5668","authenticated-orcid":false,"given":"D\u00e1vid Kursz\u00e1n","family":"J\u00e1sz","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Medical School, University of P\u00e9cs, 7632 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0983-2092","authenticated-orcid":false,"given":"T\u00fcnde","family":"Minier","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Medical School, University of P\u00e9cs, 7632 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di\u00e1na","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Immunology and Biotechnology, Medical School, University of P\u00e9cs, 7632 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9597-8487","authenticated-orcid":false,"given":"Szabina","family":"Erd\u0151-Bony\u00e1r","sequence":"additional","affiliation":[{"name":"Department of Immunology and Biotechnology, Medical School, University of P\u00e9cs, 7632 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0134-8127","authenticated-orcid":false,"given":"T\u00edmea","family":"Berki","sequence":"additional","affiliation":[{"name":"Department of Immunology and Biotechnology, Medical School, University of P\u00e9cs, 7632 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8500-2918","authenticated-orcid":false,"given":"G\u00e1bor","family":"Kum\u00e1novics","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Medical School, University of P\u00e9cs, 7632 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,13]]},"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","first-page":"202","article-title":"Scleroderma (Systemic Sclerosis): Classification, Subsets and Pathogenesis","volume":"15","author":"LeRoy","year":"1988","journal-title":"J. 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