Ocrelizumab Depletes CD20+ T Cells in Multiple Sclerosis Patients

Gingele, Stefan; Jacobus, Thais Langer; Konen, Franz Felix; Hümmert, Martin W.; Sühs, Kurt‐Wolfram; Schwenkenbecher, Philipp; Ahlbrecht, Jonas; Möhn, Nora; Müschen, Lars Hendrik; Bönig, Lena; Alvermann, Sascha; Schmidt, Reinhold; Stangel, Martin; Jacobs, Roland; Skripuletz, Thomas

doi:10.3390/cells8010012

Cited by 102 publications

(101 citation statements)

References 16 publications

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“…Although typically associated with B cells, CD20 is also expressed on a subset of highly activated proinflammatory T cells and is typically found in memory T cell populations (35,36,42). CD20 + T cells are reported to be increased in MS patients (35,36), are present in MS lesions (43), and are reduced by anti-CD20 mAb therapies (35,42,44). The expression of CD20 was therefore measured on ex vivo antigen-specific CD8 + T cells (SI Appendix, Fig.…”

Section: Resultsmentioning

confidence: 99%

Anti-CD20 therapy depletes activated myelin-specific CD8⁺T cells in multiple sclerosis

Sabatino

Wilson

Calabresi³

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

103

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CD8 + T cells are believed to play an important role in multiple sclerosis (MS), yet their role in MS pathogenesis remains poorly defined. Although myelin proteins are considered potential autoantigenic targets, prior studies of myelin-reactive CD8 + T cells in MS have relied on in vitro stimulation, thereby limiting accurate measurement of their ex vivo precursor frequencies and phenotypes. Peptide:MHC I tetramers were used to identify and validate 5 myelin CD8 + T cell epitopes, including 2 newly described determinants in humans. The validated tetramers were used to measure the ex vivo precursor frequencies and phenotypes of myelin-specific CD8 + T cells in the peripheral blood of untreated MS patients and HLA allele-matched healthy controls. In parallel, CD8 + T cell responses against immunodominant influenza epitopes were also measured. There were no differences in ex vivo frequencies of tetramerpositive myelin-specific CD8 + T cells between MS patients and control subjects. An increased proportion of myelin-specific CD8 + T cells in MS patients exhibited a memory phenotype and expressed CD20 compared to control subjects, while there were no phenotypic differences observed among influenza-specific CD8 + T cells. Longitudinal assessments were also measured in a subset of MS patients subsequently treated with anti-CD20 monoclonal antibody therapy. The proportion of memory and CD20 + CD8 + T cells specific for certain myelin but not influenza epitopes was significantly reduced following anti-CD20 treatment. This study, representing a characterization of unmanipulated myelin-reactive CD8 + T cells in MS, indicates these cells may be attractive targets in MS therapy. multiple sclerosis | CD8 + T cells | myelin antigen | anti-CD20 therapy

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Section: Resultsmentioning

confidence: 99%

Anti-CD20 therapy depletes activated myelin-specific CD8⁺T cells in multiple sclerosis

Sabatino

Wilson

Calabresi³

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

103

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“…In November 2019, EMA also recommended a restrictive use of alemtuzumab (Lemtrada) for RRMS patients with highly active disease despite treatment with at least one disease-modifying therapy [205]. Interestingly, Gingele et al recently reported that ocrelizumab, a humanized mAb targeting CD20 approved in 2017 for relapsing MS and PPMS and thought to specifically target B cells [206,207], was also effective in depleting a highly activated CD20 + T cell subset producing inflammatory cytokines [208]. Since CD20 + inflammatory T cells are present in the peripheral blood and brain of MS patients [208,209], their depletion may account for the efficacy of ocralizumab therapy.…”

Section: T Cell Targeting Therapymentioning

confidence: 99%

T Helper Cells: The Modulators of Inflammation in Multiple Sclerosis

Kunkl

Frascolla

Amormino

et al. 2020

Cells

142

107

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Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by the progressive loss of axonal myelin in several areas of the central nervous system (CNS) that is responsible for clinical symptoms such as muscle spasms, optic neuritis, and paralysis. The progress made in more than one decade of research in animal models of MS for clarifying the pathophysiology of MS disease validated the concept that MS is an autoimmune inflammatory disorder caused by the recruitment in the CNS of self-reactive lymphocytes, mainly CD4+ T cells. Indeed, high levels of T helper (Th) cells and related cytokines and chemokines have been found in CNS lesions and in cerebrospinal fluid (CSF) of MS patients, thus contributing to the breakdown of the blood–brain barrier (BBB), the activation of resident astrocytes and microglia, and finally the outcome of neuroinflammation. To date, several types of Th cells have been discovered and designated according to the secreted lineage-defining cytokines. Interestingly, Th1, Th17, Th1-like Th17, Th9, and Th22 have been associated with MS. In this review, we discuss the role and interplay of different Th cell subpopulations and their lineage-defining cytokines in modulating the inflammatory responses in MS and the approved as well as the novel therapeutic approaches targeting T lymphocytes in the treatment of the disease.

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“…Ocrelizumab has been approved for the treatment of both RRMS and early PPMS [56,57]. Following the first infusion, B cells were largely depleted after 2 weeks and remained depleted throughout treatment.…”

Section: Ocrelizumab and Rituximabmentioning

confidence: 99%

Effects of disease-modifying therapy on peripheral leukocytes in patients with multiple sclerosis

et al. 2020

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Modern disease-modifying therapies (DMTs) in multiple sclerosis (MS) have variable modes of action and selectively suppress or modulate the immune system. In this review, we summarize the predicted and intended as well as unwanted adverse effects on leukocytes in peripheral blood as a result of treatment with DMTs for MS. We link changes in laboratory tests to the possible therapeutic risks that include secondary autoimmunity, infections, and impaired response to vaccinations. Profound knowledge of the intended effects on leukocyte counts, in particular lymphocytes, explained by the mode of action, and adverse effects which may require additional laboratory and clinical vigilance or even drug discontinuation, is needed when prescribing DMTs to treat patients with MS.

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Ocrelizumab Depletes CD20+ T Cells in Multiple Sclerosis Patients

Cited by 102 publications

References 16 publications

Anti-CD20 therapy depletes activated myelin-specific CD8⁺T cells in multiple sclerosis

Anti-CD20 therapy depletes activated myelin-specific CD8⁺T cells in multiple sclerosis

T Helper Cells: The Modulators of Inflammation in Multiple Sclerosis

Effects of disease-modifying therapy on peripheral leukocytes in patients with multiple sclerosis

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Ocrelizumab Depletes CD20+ T Cells in Multiple Sclerosis Patients

Cited by 102 publications

References 16 publications

Anti-CD20 therapy depletes activated myelin-specific CD8+T cells in multiple sclerosis

Anti-CD20 therapy depletes activated myelin-specific CD8+T cells in multiple sclerosis

T Helper Cells: The Modulators of Inflammation in Multiple Sclerosis

Effects of disease-modifying therapy on peripheral leukocytes in patients with multiple sclerosis

Contact Info

Product

Resources

About

Anti-CD20 therapy depletes activated myelin-specific CD8⁺T cells in multiple sclerosis

Anti-CD20 therapy depletes activated myelin-specific CD8⁺T cells in multiple sclerosis