Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2023 Feb 7;120(6):e2221544120.
doi: 10.1073/pnas.2221544120. Epub 2023 Jan 31.

Learning multiple sclerosis immunopathogenesis from anti-CD20 therapy

Michael Heming  1 , Heinz Wiendl  1
Affiliations
Comment

Learning multiple sclerosis immunopathogenesis from anti-CD20 therapy

Michael Heming et al. Proc Natl Acad Sci U S A. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors have organizational affiliations to disclose, H.W. receives honoraria for acting as a member of Scientific Advisory Boards from Abbvie, Alexion, Argenx, Bristol Myers Squibb/Celgene, Janssen, Merck, Novartis, Sandoz, Speaker honoraria and travel support from Alexion, Biogen, Bristol Myers Squibb, Genzyme, Merck, Neurodiem, Novartis, Roche, TEVA, WebMD Global. H.W. is acting as a paid consultant for Abbvie, Actelion, Argenx, BD, Biogen, Bristol Myers Squibb, EMD Serono, Fondazione Cariplo, Gossamer Bio, Idorsia, Immunic, Immunovant, Janssen, Lundbeck, Merck, NexGen, Novartis, PSI CRO, Roche, Sanofi, Swiss MS Society, UCB, Worldwide Clinical Trials. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgesellschaft, Deutsche Myasthenie Gesellschaft e.V., Alexion, Amicus Therapeutics Inc., Argenx, Biogen, CSL Behring, F. Hoffmann-La Roche, Genzyme, Merck KgaA, Novartis, Roche Pharma, UCB Biopharma.

Figures

Fig. 1.
Fig. 1.
Multifaceted effects of anti-CD20 treatment in MS. (A) Shinoda et al. (19) show that CD20dim T cells, particularly CD20dim CD8+ T cells, correlate negatively with MRI disease activity before treatment and may also predict early MRI disease activity after treatment. Repopulating CD20dim CD8+ T cells exhibit a less proinflammatory phenotype following anti-CD20 treatment. Reconstituting B cells are mainly transitional B cells (CD24high and CD38high) with an anti-inflammatory (reduced IL-6 expression and increased IL-10 expression) and activated (CD86, CD95, and CD71) phenotype and reduced CNS homing properties (reduced ALCAM expression). (B) Proinflammatory B cells produce antibodies and proinflammatory cytokines that contribute to the CNS-directed autoimmune response. Additionally, they interact with CD4+ Th1 cells, which leads to an autoproliferation of Th1 cells. Proinflammatory CD20dim CD8+ T cells acquire CD20 from B cells via trogocytosis and trigger relapses in MS. Anti-CD20 treatment depletes B cells, thereby reducing both proinflammatory B cells and T cell autoproliferation, and proinflammatory CD20dim CD8+ T cells. The figure was partly created using Servier Medical Art, provided by Servier, licensed under a Create Commons Attribution 3.0 unported license.
See this image and copyright information in PMC

Comment on

  • Differential effects of anti-CD20 therapy on CD4 and CD8 T cells and implication of CD20-expressing CD8 T cells in MS disease activity.
    Shinoda K, Li R, Rezk A, Mexhitaj I, Patterson KR, Kakara M, Zuroff L, Bennett JL, von Büdingen HC, Carruthers R, Edwards KR, Fallis R, Giacomini PS, Greenberg BM, Hafler DA, Ionete C, Kaunzner UW, Lock CB, Longbrake EE, Pardo G, Piehl F, Weber MS, Ziemssen T, Jacobs D, Gelfand JM, Cross AH, Cameron B, Musch B, Winger RC, Jia X, Harp CT, Herman A, Bar-Or A. Shinoda K, et al. Proc Natl Acad Sci U S A. 2023 Jan 17;120(3):e2207291120. doi: 10.1073/pnas.2207291120. Epub 2023 Jan 12. Proc Natl Acad Sci U S A. 2023. PMID: 36634138 Free PMC article.

References

    1. Lublin F. D., et al. , How patients with multiple sclerosis acquire disability. Brain 145, 3147–3161 (2022). - PMC - PubMed
    1. Meyer Zu Hörste G., Gross C. C., Klotz L., Schwab N., Wiendl H., Next-generation neuroimmunology: New technologies to understand central nervous system autoimmunity. Trends Immunol. 41, 341–354 (2020). - PubMed
    1. Schneider-Hohendorf T., et al. , VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM-adhesion of TH17 cells. J. Exp. Med. 211, 1833–1846 (2014). - PMC - PubMed
    1. Yednock T. A., et al. , Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 356, 63–66 (1992). - PubMed
    1. Wiendl H., et al. , Specific patterns of immune cell dynamics may explain the early onset and prolonged efficacy of cladribine tablets: A MAGNIFY-MS substudy. Neurol. Neuroimmunol. Neuroinflamm. 10, e200048 (2023). - PMC - PubMed

Publication types

Substances