{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:17:42Z","timestamp":1778221062021,"version":"3.51.4"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Systemic lupus erythematosus (SLE) is characterized by fluctuating activity and unpredictable flares that contribute to cumulative organ damage. Biomarkers capable of identifying patients at risk of near-term disease reactivation are needed. Interleukin-6 (IL-6) has been associated with SLE activity, but its prospective predictive value remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a prospective, longitudinal, single-center study (2017\u20132023) including 188 adult with SLE. Serum IL-6 levels were measured at routine and unscheduled visits. Patients were categorized using a prespecified cutoff of 5 pg\/mL. Disease activity was assessed using SLEDAI-2K (with values &amp;gt;4 suggesting active disease) and organ-specific manifestations. Prospective (lagged) associations were analyzed using the log-rank test. Discriminative performance was evaluated using ROC analyses and multivariable models adjusted for clinical confounders. IL-6 was compared with anti\u2013double-stranded DNA antibodies and complement components C3 and C4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During follow-up, 48% of patients had IL-6 levels &amp;gt;5 pg\/mL. IL-6 &amp;gt;5 pg\/mL was associated with a shorter time to subsequent flare, with a median time to SLEDAI-2K &amp;gt;4 that was 10 months shorter. Elevated IL-6 also predicted arthritis, nephritis, serositis, and hematologic manifestations. Concurrently, IL-6 demonstrated greater discriminative performance than anti-dsDNA, C3, and C4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Elevated circulating IL-6 levels are associated with short-term disease reactivation in SLE and may complement established biomarkers in longitudinal disease assessment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1825342","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:55:24Z","timestamp":1778219724000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated interleukin-6 levels predict short-term flare in systemic lupus erythematosus"],"prefix":"10.3389","volume":"17","author":[{"given":"Borja del Carmelo","family":"Gracia Tello","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Hospital Cl\u00ednico Universitario Lozano Blesa","place":["Zaragoza, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Miguel","family":"Garc\u00eda-Bru\u00f1\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Cl\u00ednico Universitario Lozano Blesa","place":["Zaragoza, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Corredor","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Cl\u00ednico Universitario Lozano Blesa","place":["Zaragoza, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Allue Fantova","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Hospital General San Jorge","place":["Huesca, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva Ma","family":"Calvo Beguer\u00eda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital General San Jorge","place":["Huesca, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rub\u00e9n","family":"Garc\u00eda-Mu\u00f1\u00edo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Cl\u00ednico Universitario Lozano Blesa","place":["Zaragoza, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"P\u00e9rez Abad","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Cl\u00ednico Universitario Lozano Blesa","place":["Zaragoza, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jimena","family":"Aramburu Llorente","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Cl\u00ednico Universitario Lozano Blesa","place":["Zaragoza, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Martinez Muriel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Cl\u00ednico Universitario Lozano Blesa","place":["Zaragoza, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Vidales Migu\u00e9lez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Cl\u00ednico Universitario Lozano Blesa","place":["Zaragoza, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roxanna Alexandra","family":"Morante Mendoza","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario Miguel Servet","place":["Zaragoza, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Mart\u00ednez Artigot","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Cl\u00ednico Universitario Lozano Blesa","place":["Zaragoza, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelia","family":"Chicano Nieto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital General San Jorge","place":["Huesca, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"\u00c1lvarez Troncoso","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario La Paz","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Martinez-Lostao","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Cl\u00ednico Universitario Lozano Blesa","place":["Zaragoza, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adela","family":"Mar\u00edn Ballv\u00e9","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Cl\u00ednico Universitario Lozano Blesa","place":["Zaragoza, 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