{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T07:12:20Z","timestamp":1778224340273,"version":"3.51.4"},"reference-count":48,"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>Introduction<\/jats:title>\n                    <jats:p>Maintenance immunotherapy is effective in AQP4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD), but how mechanistically distinct maintenance therapies organize the remission immune landscape and its relationship to neurological disability remains poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed integrated multiparameter flow cytometry and plasma cytokine profiling in serial remission samples (up to three per patient) from 28 patients receiving rituximab (RTX, n = 14) or azathioprine (AZA, n = 14). Between-treatment comparisons, within-treatment coupling analyses, and disability-associated immune analyses were conducted using age-adjusted patient-clustered regression models with prespecified false discovery rate control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>RTX showed clear target engagement, characterized by profound B-cell depletion, gradual post-infusion reconstitution, and sustained reduction of natural killer T (NKT)-like cells. Beyond lineage depletion, RTX was associated with regulatory remodeling, including a memory-skewed regulatory T (Treg) phenotype and a lower effector-to-regulatory balance. In B-detectable RTX samples, the reconstituting B-cell compartment was transitional\/naive-skewed with marked suppression of memory B cells. Although remission-phase cytokines were broadly low, interferon gamma-induced protein 10\/CXC motif chemokine ligand 10 (IP-10\/CXCL10) remained selectively elevated under RTX. Importantly, remission immune architecture differed by therapy: AZA showed a T cell immunoreceptor with Ig and ITIM domains (TIGIT)-linked regulatory disability axis, whereas RTX showed disability coupling to soluble inflammatory mediators, particularly interleukin-6 (IL-6) and IP-10.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Mechanistically distinct maintenance therapies impose divergent remission immune architectures in NMOSD. These findings support a treatment-aware framework for biomarker interpretation and suggest that remission monitoring should consider therapy-specific immune networks rather than isolated immune markers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1834992","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:37:55Z","timestamp":1778222275000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct remission immune architectures under rituximab and azathioprine in AQP4-IgG-positive neuromyelitis optica spectrum disorder"],"prefix":"10.3389","volume":"17","author":[{"given":"Wangyong","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine.","place":["Seoul, Republic of 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