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In this study, we collected peripheral blood mononuclear cells (PBMCs) from NMOSD patients during steroid tapering and performed bulk RNA sequencing to analyze changes in immune dynamics caused by steroid reduction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PBMCs were collected at 3\u20135 timepoints from 10 NMOSD patients at our hospital (including one relapse case), and bulk RNA sequencing was performed. All patients were positive for anti-AQP4 antibodies and had no history of biologic use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In one relapsed patient, gene groups with decreased expression at relapse were observed predominantly in monocytes, with upregulation in anti-inflammatory pathways such as IL-10, while the upregulated genes were related to interferon signaling. Moreover, after steroid tapering, in non-relapsed patients, genes with increased expression were enriched in inflammatory pathways, represented by interferon signaling, while genes with decreased expression were enriched in pathways related to IL-10 and glucocorticoid receptors. Weighted gene co-expression network analysis identified modules that correlated with steroid dosage, and the modules inversely correlated with steroid dosage were enriched in monocytes, with marked immune signature of interferon pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study identified peripheral blood transcriptome signatures that could lead to the identification of clinically relevant NMOSD disease activity biomarkers, and further highlights the pivotal role of interferon and IL-10 signaling in NMOSD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1508977","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T05:12:02Z","timestamp":1738559522000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Transcriptome signature in the blood of neuromyelitis optica spectrum disorder under steroid tapering"],"prefix":"10.3389","volume":"16","author":[{"given":"Ryohei","family":"Yamamura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Yasumizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Yata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keigo","family":"Kihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Motooka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Shiraishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Beppu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Murata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoshi","family":"Koizumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itsuki","family":"Sano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Koda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsusada","family":"Okuno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Mochizuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13836","article-title":"Progress in treatment of neuromyelitis optica spectrum disorders (Nmosd): novel insights into therapeutic possibilities in nmosd","volume":"28","author":"Shi","year":"2022","journal-title":"CNS Neurosci Ther"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102166","article-title":"Efficacy and safety of monoclonal antibody therapy in neuromyelitis optica spectrum disorders: evidence from randomized controlled trials","volume":"43","author":"Xue","year":"2020","journal-title":"Mult Scler Relat Disord"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(04)17551-x","article-title":"A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis","volume":"364","author":"Lennon","year":"2004","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-023-11634-0","article-title":"Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (Nmosd) - revised recommendations of the neuromyelitis optica study group (Nemos). 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