{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T10:08:10Z","timestamp":1789207690106,"version":"build-2803163510"},"reference-count":38,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"unspecified","delay-in-days":72,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["U01DP005120"],"award-info":[{"award-number":["U01DP005120"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Lupus Sci Med"],"accepted":{"date-parts":[[2026,8,11]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Identify whether changes in metabolite abundance are associated with SLE flare remission and changes in DNA methylation (DNAm).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      40 multiethnic patients with SLE were recruited during a rheumatologist-confirmed flare and returned to the clinic 3\u2009months later. Per visit, we obtained blood samples and generated untargeted metabolomics (ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry) and DNAm (Illumina EPIC array) profiles. We identified chemical features whose change between visits was associated with remission at the follow-up visit using the\n                      <jats:italic>limma<\/jats:italic>\n                      package and a time \u00d7 remission interaction term, adjusting for follow-up time and medications. We tested for correlations between changes in significant chemical features and DNAm at 291 sites previously associated with remission.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      16 patients with SLE were in remission at the follow-up visit. Remitters and non-remitters had similar demographics and disease activity at baseline. We identified 62 chemical features whose changes over time were associated with remission. 19 were assigned a putative consensus chemical formula. Two were confirmed with reference standards\u2014adenosine (interaction coefficient (\u03b2): 2.29, 95% CI 1.44 to 3.14) and bilirubin (\u03b2: 2.02, 95%\u2009CI 1.09 to 2.94). We identified 23 significantly correlated chemical feature-DNAm pairs (p&lt;0.05\/62\u00d7291). This included a strong correlation between adenosine and four DNAm sites, including three within immune-related genes\n                      <jats:italic>, EBF1<\/jats:italic>\n                      (r=\u22120.77, p=1.35\u00d710\n                      <jats:sup>\u22127<\/jats:sup>\n                      ),\n                      <jats:italic>IL12B<\/jats:italic>\n                      (r=0.69, p=1.87\u00d710\n                      <jats:sup>\u22126<\/jats:sup>\n                      ) and\n                      <jats:italic>GRAMD1C<\/jats:italic>\n                      (r=\u22120.71, p=1.00\u00d710\n                      <jats:sup>\u22126<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Changes in chemical features, including confirmed metabolites bilirubin and adenosine, were associated with flare remission and changes in DNAm at SLE-relevant loci. Metabolites and their correlations with DNAm might serve as indicators of immune function and improve our knowledge of determinants of response to treatment. Future studies are needed to confirm the identities of metabolites and robustness of findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/lupus-2026-002017","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:40:44Z","timestamp":1789206044000},"page":"e002017","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated metabolomics and DNA methylation signatures and their association with flare remission in SLE"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0854-4219","authenticated-orcid":false,"given":"Mary","family":"Horton","sequence":"first","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan","family":"Johnson","sequence":"additional","affiliation":[{"name":"Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten E","family":"Overdahl","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Research Center, National Institute of Environmental Health Sciences, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Nititham","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly E","family":"Taylor","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, University of California San Francisco, San Francisco, California, 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Dall\u2019Era","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa F","family":"Barcellos","sequence":"additional","affiliation":[{"name":"Division of Epidemiology\/Biostatistics, School of Public Health, University of California, Berkeley, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Liang","family":"Li","sequence":"additional","affiliation":[{"name":"Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan K","family":"Jarmusch","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Research Center, National Institute of Environmental Health Sciences, 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