{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T11:37:56Z","timestamp":1788089876706,"version":"build-2803163510"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"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>Background<\/jats:title>\n                    <jats:p>Alemtuzumab is an immune reconstitution therapy (IRT) approved for highly active relapsing\u2013remitting multiple sclerosis (RRMS). Notably, the differential reconstitution of B and T cells after alemtuzumab may trigger paradoxical B\u2013cell\u2013mediated inflammation and secondary autoimmunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Report<\/jats:title>\n                    <jats:p>We describe the case of a 44-year-old woman with RRMS who experienced a severe, steroid-resistant relapse nine months after her second alemtuzumab cycle. Lymphocyte subtyping revealed disproportionate B-cell repopulation, suggesting a B-cell\u2013mediated immunopathogenesis. Early ocrelizumab switch resulted in rapid clinical and radiological recovery and sustained stability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Literature review<\/jats:title>\n                    <jats:p>We conducted a narrative review of early and paradoxical disease reactivation after alemtuzumab, identifying common features: early onset, poor steroid response, large or tumefactive lesions, and marked B-cell hyperrepopulation. Anti-CD20 therapy often induced rapid remission. These findings may suggest a distinct B-cell\u2013driven mechanism of inflammation. Prior exposure to fingolimod has been observed in several cases, but does not uniformly account for the observed phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This case contributes to the growing evidence that a subset of patients may experience B-cell\u2013driven inflammatory reactivation after alemtuzumab treatment. Lymphocyte subtyping should be performed, and a predominance of CD19\n                      <jats:sup>+<\/jats:sup>\n                      B cells can guide a timely therapeutic switch to anti-CD20 therapy. Further studies are needed to define whether this represents a distinct post-IRT immunopathological entity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1710669","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T14:38:57Z","timestamp":1767883137000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["B-cell\u2013driven relapse and anti-CD20 rescue therapy after Alemtuzumab in RRMS: case report and literature review"],"prefix":"10.3389","volume":"16","author":[{"given":"Pietro Antonio","family":"Bruno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Barone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Pascarella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Luigi","family":"Lanza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Tinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Gambardella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Valentino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1507","article-title":"Multiple sclerosis: a complicated picture of autoimmunity","volume":"8","author":"McFarland","year":"2007","journal-title":"Nat Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e00362","DOI":"10.1002\/brb3.362","article-title":"An update on immunopathogenesis, diagnosis, and treatment of multiple 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