{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T16:02:52Z","timestamp":1776441772272,"version":"3.51.2"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC82371351"],"award-info":[{"award-number":["NSFC82371351"]}],"id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>AQP4-IgG-seronegative Neuromyelitis Optica Spectrum Disorders (AQP4-IgG-seronegative NMOSD) represent a distinct and rare subtype of Neuromyelitis Optica Spectrum Disorders (NMOSD). Diagnosis and management of this condition pose significant challenges in clinical practice. Here, we present two cases of AQP4-IgG-seronegative NMOSD, which demonstrated a favorable response to personalized ofatumumab (OFA) therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two patients, confirmed negative for both AQP4-IgG and MOG-IgG by cell-based assay methods and meeting the diagnostic criteria for AQP4-IgG-negative NMOSD according to the 2015 international criteria were treated with monthly subcutaneous OFA (20 mg). Clinical status was monitored using the Expanded Disability Status Scale (EDSS), B-cell depletion (CD19+%), MRI, and serum neurofilament light chain (NfL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Both patients (a 13-year-old male and a 31-year-old female) had severe disability (EDSS 6.5 and 5.5, respectively) and poor response to initial steroids\/IVIG. After OFA initiation, both achieved rapid and sustained B-cell depletion (CD19+% 0.00-0.11%). Symptoms remained stable and gradually improved, imaging showing marked reduction or resolution of lesions and EDSS scores decreasing by \u22653 points (to 2.0 in both patients) over 18\u201320 months of follow-up. No clinical relapses or serious adverse events (e.g., infections, significant IgG reduction) occurred. After 12 months of monthly dosing, the interval was successfully extended to every two months in both patients while maintaining efficacy and B-cell depletion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Subcutaneous OFA demonstrated sustained efficacy and a favorable safety profile as a long-term therapy for AQP4-IgG-seronegative NMOSD in this case series. It facilitated significant functional recovery, prevented relapses, and enabled personalized, extended dosing intervals. These preliminary findings support OFA as a promising, convenient therapeutic option for AQP4-IgG-seronegative NMOSD, meriting further investigation in larger prospective studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1760491","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T05:26:42Z","timestamp":1773379602000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel B-Cell targeting therapy with subcutaneous ofatumumab in AQP4-IgG-seronegative Neuromyelitis Optica Spectrum Disorders: efficacy and personalized dosing"],"prefix":"10.3389","volume":"17","author":[{"given":"Xuetao","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]},{"name":"Department of Neurology, Shandong Provincial Hospital, Shandong University","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danqing","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]},{"name":"Department of Geriatric Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baojie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunjuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shougang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001729","article-title":"International consensus diagnostic criteria for neuromyelitis optica spectrum disorders","volume":"85","author":"Wingerchuk","year":"2015","journal-title":"Neurology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-017-8596-7","article-title":"What proportion of AQP4-IgG-negative NMO spectrum disorder patients are MOG-IgG positive? 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