{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T12:38:25Z","timestamp":1786451905119,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Oxidative stress plays an important role in systemic lupus erythematosus (SLE). To elucidate whether it is already present in early phases, we investigate oxidative stress-related genes in incomplete SLE (iSLE) and quiescent SLE (qSLE, inactive disease), as well as the effect of nuclear factor erythroid-derived 2-like 2 (NRF2) activators on NRF2-related genes in peripheral blood mononuclear cells (PBMCs) and HaCaT keratinocytes. In total, 28 qSLE patients, 29 iSLE patients and 21 age- and sex-matched healthy controls (HCs) were included. Serum free thiols, reactive oxygen species (ROS) levels and NRF2-related antioxidant gene expression were measured. Furthermore, PBMCs and HaCaT keratinocytes were treated with the NRF2 activators sulforaphane (SFN) and dimethyl fumarate (DMF) in vitro to assess expression of antioxidant genes. Finally, NRF2 and Heme oxygenase-1 (HMOX1) proteins in non-sun-exposed skin sections were assessed. Thiols were significantly lower in qSLE patients compared to HCs. In whole blood, Kelch-like ECH-associating protein 1 (KEAP1) and catalase (CAT) mRNA levels were significantly reduced in iSLE and qSLE. Treatment with SFN or DMF in PBMCs upregulated HMOX1 and NAD(P)H quinone dehydrogenase-1 (NQO1) mRNA expression and downregulated CAT expression. In HaCaT cells, mRNA expression of HMOX1, NQO1 and thioredoxin was upregulated. There were no differences in protein expression of NRF2 and HMOX1 in skin tissues. In conclusion, in qSLE patients, oxidative stress is elevated, while antioxidant capacity is decreased. A similar trend, although not significant, is seen in iSLE patients, which indicates that redox imbalances are already present in early phases, but not as obvious as in established SLE. NRF2 activators upregulate antioxidant gene expression in PBMCs and HaCaT cells, highlighting their potential role to modulate oxidative stress pathways in SLE.<\/jats:p>","DOI":"10.3390\/antiox15080995","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:51:36Z","timestamp":1786449096000},"page":"995","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oxidative Stress and NRF2-Mediated Redox Regulation in Incomplete Systemic Lupus Erythematosus and Systemic Lupus Erythematosus"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9274-1372","authenticated-orcid":false,"given":"Lu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Henning","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6670-1577","authenticated-orcid":false,"given":"Harry van","family":"Goor","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrika","family":"Bootsma","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berber","family":"Doornbos-van der Meer","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Westra","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0218-9364","authenticated-orcid":false,"given":"Karina de","family":"Leeuw","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1016\/S0140-6736(24)00398-2","article-title":"Systemic lupus erythematosus","volume":"403","author":"Hoi","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1001\/jama.2024.2315","article-title":"Systemic Lupus Erythematosus: A Review","volume":"331","author":"Siegel","year":"2024","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1136\/annrheumdis-2020-218272","article-title":"Update omicronn the diagnosis and management of systemic lupus erythematosus","volume":"80","author":"Fanouriakis","year":"2021","journal-title":"Ann. 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