{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:41:11Z","timestamp":1784302871044,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ACR Open Rheumatology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the predictive performance of inflammatory biomarkers, including C\u2010reactive protein (CRP) and Krebs von den Lungen 6 (KL\u20106), for the development of progressive pulmonary fibrosis (PPF) in patients with systemic sclerosis (SSc)\u2013associated interstitial lung disease (ILD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 135 patients with SSc\u2010ILD were retrospectively selected from a single\u2010center prospective registry. The predictive performance of individual biomarkers and their combinations for PPF development was evaluated using area under the curve (AUC) values from receiver operating characteristic analysis. A time\u2010varying Cox proportional hazards model was used to assess the prognostic significance of near\u2010term dynamic changes in KL\u20106 levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During a median follow\u2010up of 43 months, 26 patients (19%) developed PPF. Baseline CRP and KL\u20106 levels did not correlate with each other. Patients with high baseline KL\u20106 (\u22651,000 U\/mL) had more extensive ILD and reduced forced vital capacity compared to those with low levels. Baseline KL\u20106 demonstrated superior predictive performance for ILD progression (with the highest AUC) compared to CRP. The PPF\u2010free survival rate was significantly lower in the high KL\u20106 group than in the low KL\u20106 group (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.02). A doubling of KL\u20106 levels at any time from 12 months to 6 months before PPF assessment or censoring was associated with a significantly higher risk of subsequent PPF development (hazard ratio 1.66 [95% confidence interval 1.13\u20132.45]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Baseline KL\u20106 and CRP values identify distinct subsets of SSc\u2010ILD patients. Elevated baseline KL\u20106 levels and a significant rise over the subsequent six months are associated with an increased risk of PPF, supporting their potential as prognostic biomarkers.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/acr290013-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  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