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Effects of Anti-CD20 Antibody Therapy on Immune Cell Dynamics in Relapsing-Remitting Multiple Sclerosis
AG. Willison, R. Hagler, M. Weise, S. Elben, N. Huntemann, L. Masanneck, S. Pfeuffer, S. Lichtenberg, KS. Golombeck, LM. Preuth, L. Rolfes, M. Öztürk, T. Ruck, N. Melzer, M. Korsen, SL. Hauser, HP. Hartung, PA. Lang, M. Pawlitzki, S. Räuber, SG. Meuth
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
Project number: MOMB157A_FVSP002
Novartis Deutschland GmbH
NLK
Directory of Open Access Journals
od 2012
Free Medical Journals
od 2012
PubMed Central
od 2012
Europe PubMed Central
od 2012
ProQuest Central
od 2012-03-01
Open Access Digital Library
od 2012-01-01
Open Access Digital Library
od 2012-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2012
PubMed
40214505
DOI
10.3390/cells14070552
Knihovny.cz E-zdroje
- MeSH
- antigeny CD20 * imunologie MeSH
- B-lymfocyty imunologie účinky léků MeSH
- buňky NK imunologie MeSH
- dospělí MeSH
- humanizované monoklonální protilátky * terapeutické užití farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- longitudinální studie MeSH
- relabující-remitující roztroušená skleróza * imunologie farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION: The efficacy of anti-CD20 antibodies has significantly contributed to advancing our understanding of disease pathogenesis and improved treatment outcomes in relapsing-remitting multiple sclerosis (RRMS). A comprehensive analysis of the peripheral immune cell profile, combined with prospective clinical characterization, of RRMS patients treated with ocrelizumab (OCR) or ofatumumab (OFA) was performed to further understand immune reconstitution following B-cell depletion. METHODS: REBELLION-MS is a longitudinal analysis of RRMS patients treated with either OCR (n = 34) or OFA (n = 25). Analysis of B, T, natural killer (NK) and natural killer T (NKT) cells at baseline, month 1, and 12 was performed by multidimensional flow cytometry. Data were analyzed by conventional gating and unsupervised computational approaches. In parallel, different clinical parameters were longitudinally assessed. Twenty treatment-naïve age/sex-matched RRMS patients were included as the control cohort. RESULTS: B-cell depletion by OCR and OFA resulted in significant reductions in CD20+ T and B cells as well as B-cell subsets, alongside an expansion of CD5+CD19+CD20- B cells, while also elevating exhaustion markers (CTLA-4, PD-1, TIGIT, TIM-3) across T, B, NK, and NKT cells. Additionally, regulatory T-cell (TREG) numbers increased, especially in OCR-treated patients, and reductions in double-negative (CD3+CD4-CD8-) T cells (DN T cells) were observed, with these DN T cells having higher CD20 expression compared to CD4 or CD8 positive T cells. These immune profile changes correlated with clinical parameters, suggesting pathophysiological relevance in RRMS. CONCLUSIONS: Our interim data add weight to the argumentation that the exhaustion/activation markers, notably TIGIT, may be relevant to the pathogenesis of MS. In addition, we identify a potentially interesting increase in the expression of CD5+ on B cells. Finally, we identified a population of double-negative T cells (KLRG1+HLADR+, in particular) that is associated with MS activity and decreased with CD20 depletion.
Brain and Mind Center University of Sydney Sydney NSW 2050 Australia
Department of Neurology Medical University of Vienna 1090 Vienna Austria
Department of Neurology Palacky University 771 46 Olomouc Czech Republic
Citace poskytuje Crossref.org
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