Proinflammatory CD20
            <sup>+</sup>
            T cells contribute to CNS-directed autoimmunity

Ochs, Jasmin; Nissimov, Nitzan; Torke, Sebastian; Freier, Marie; Grondey, Katja; Koch, Julian; Klein, Matthias; Feldmann, Linda; Gudd, Cathrin; Bopp, Tobias; Häusser‐Kinzel, Silke; Weber, Martin

doi:10.1126/scitranslmed.abi4632

Cited by 42 publications

(53 citation statements)

References 47 publications

(74 reference statements)

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“…As the B-cells are the main expressors of the CD20 marker, the anti-CD20 monoclonal antibodies primarily affect the B-cell compartment of the immune system—although some recent literature suggests that their effectiveness in MS may stem from their effect on subsets of ‘rogue’ CD20+ T cells 50. Similar to pwMS on other DMTs, the COVID-19 vaccines’ immunogenicity among pwMS on aCD20 could be considered a translation of the previously-determined B-cell and T-cell dynamics in them,34 51 based on which the current guidelines recommended a 12-to-36-week window between aCD20 infusion and COVID-19 vaccination 1–4.…”

Section: Resultsmentioning

confidence: 99%

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis

Etemadifar

Nouri

Pitzalis

et al. 2022

J Neurol Neurosurg Psychiatry

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Studies among people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have provided adequate evidence for an appraisal of COVID-19 vaccination policies among them. To synthesise the available evidence addressing the effect of MS DMTs on COVID-19 vaccines’ immunogenicity and effectiveness, following the Cochrane guidelines, we systematically reviewed all observational studies available in MEDLINE, Scopus, Web of Science, MedRxiv and Google Scholar from January 2021 to January 2022 and extracted their relevant data. Immunogenicity data were then synthesised in a quantitative, and other data in a qualitative manner. Evidence from 28 studies suggests extensively lower B-cell responses in sphingosine-1-phosphate receptor modulator (S1PRM) treated and anti-CD20 (aCD20) treated, and lower T-cell responses in interferon-treated, S1PRM-treated and cladribine-treated pwMS—although most T cell evidence currently comprises of low or very low certainty. With every 10-week increase in aCD20-to-vaccine period, a 1.94-fold (95% CI 1.57 to 2.41, p<0.00001) increase in the odds of seroconversion was observed. Furthermore, the evidence points out that B-cell-depleting therapies may accelerate postvaccination humoral waning, and boosters’ immunogenicity is predictable with the same factors affecting the initial vaccination cycle. Four real-world studies further indicate that the comparative incidence/severity of breakthrough COVID-19 has been higher among the pwMS treated with S1PRM and aCD20—unlike the ones treated with other DMTs. S1PRM and aCD20 therapies were the only DMTs reducing the real-world effectiveness of COVID-19 vaccination among pwMS. Hence, it could be concluded that optimisation of humoral immunogenicity and ensuring its durability are the necessities of an effective COVID-19 vaccination policy among pwMS who receive DMTs.

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Section: Resultsmentioning

confidence: 99%

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis

Etemadifar

Nouri

Pitzalis

et al. 2022

J Neurol Neurosurg Psychiatry

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“…Recent evidence suggests that the latter may play an important role in the pathogenesis of MS and that the depletion of CD20-expressing T cells may account for part of the efficacy of anti-CD20 treatment. 15 It has further been shown that CD20 T cells repopulate at an earlier time point after pulsed BCDT than CD20 B cells. 16 Three months after rituximab infusion, counts of CD20 T cells were higher than the ones of CD20 B cells.…”

Section: Discussionmentioning

confidence: 96%

Timing of SARS-CoV-2 Vaccination Matters in People With Multiple Sclerosis on Pulsed Anti-CD20 Treatment

Woopen

Dunsche

Haase

et al. 2022

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesOur objective was to investigate cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in a cohort of people with multiple sclerosis (pwMS) on pulsed B-cell–depleting treatment (BCDT). In particular, we intended to evaluate a possible association between immune responses and the timing of vaccination under BCDT.MethodsWe conducted a cross-sectional study among pwMS on pulsed BCDT or without disease-modifying treatment after completed SARS-CoV-2 vaccination. Samples were collected during routine clinical visits at the Multiple Sclerosis Center Dresden, Germany, between June 2021 and September 2021. Blood was analyzed for SARS-CoV-2 spike protein–specific antibodies and interferon-γ release of CD4 and CD8 T cells on stimulation with spike protein peptide pools. Lymphocyte subpopulations and total immunoglobulin levels in the blood were measured as part of clinical routine.ResultsWe included 160 pwMS in our analysis, comprising 133 pwMS on BCDT (n = 132 on ocrelizumab and n = 1 on rituximab) and 27 without disease-modifying treatment. Humoral and cellular anti–SARS-CoV-2 responses were reciprocally regulated by the time between the last BCDT cycle and vaccination. Although antibody responses increased with prolonged intervals between the last BCDT cycle and vaccination, CD4 and CD8 T-cell responses were higher in pwMS vaccinated at early time points after the last BCDT cycle compared with untreated pwMS. T-cellular vaccination responses correlated with total, CD3 CD4, and partly with CD3 CD8 lymphocyte counts. Humoral responses correlated with CD19 lymphocyte counts. Status post coronavirus disease 2019 infection led to significantly increased SARS-CoV-2–specific T-cell and antibody responses.DiscussionDelaying BCDT is currently discussed as a strategy to optimize humoral responses to SARS-CoV-2 vaccination. However, T cells represent an important line of defense against SARS-CoV-2 infection as well, especially in light of emerging variants of concern. We observed enhanced CD4 and CD8 T-cellular responses in pwMS receiving vaccination at early time points after their last BCDT cycle. These data may influence clinical decision making with respect to vaccination strategies in patients receiving BCDT.

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“…CD20 protein expression is absent on T cells of human cord blood, suggesting acquisition of this molecule later in development [ 6 ]. In mice, CD20 + T cells only appear in the spleen after week 2 of age supporting this notion [ 15 ]. By co-culturing T and B cell lines, de Bruyn et al [ 6 ] were able to show an increase in CD20 expression on T cells after just 1 h. They speculated that the mechanism of this was via trogocytosis when T cells make contact with their cognate B cells [ 6 ].…”

Section: Immunobiology Of Cd20 + T Cellsmentioning

confidence: 85%

CD20+ T cells: an emerging T cell subset in human pathology

Lee

2022

Inflamm. Res.

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Introduction Although CD20 is classically a B cell marker, in the last three decades, dim expression has been noted on a subset of T cells as well that has been independently verified by a number of groups. Our understanding of these cells and their function is not well established. Methods A thorough review of original articles on CD20+T cells was undertaken of Pubmed by using combination of phrases including “CD20+”, “CD20-positive” and “T cells”. Articles in English were considered, and there was no time restriction. Results CD20+T cells express the standard T cell markers and, in comparison to CD20¯ T cells, appear to express greater inflammatory cytokines and markers of effector function. Although the ontogeny of these cells is still being established, the current theory is that CD20 may be acquired by trogocytosis from B cells. CD20+T cells may be found in healthy controls and in a wide range of pathologies including autoimmune diseases, haematological and non-haematological malignancies and human immunodeficiency virus (HIV) infections. One of the best studied diseases where these cells are found is multiple sclerosis (MS) where a number of therapeutic interventions, including anti-CD20 depletion, have been shown to effectively deplete these cells. Conclusion This review summarises the latest understanding of CD20+T cells, their presence in various diseases, their putative function and how they may be an ongoing target of CD20-depleting agents. Unfortunately, our understanding of these cells is still at its infancy and ongoing study in a wider range of pathologies is required.

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Proinflammatory CD20 ⁺ T cells contribute to CNS-directed autoimmunity

Cited by 42 publications

References 47 publications

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis

Timing of SARS-CoV-2 Vaccination Matters in People With Multiple Sclerosis on Pulsed Anti-CD20 Treatment

CD20+ T cells: an emerging T cell subset in human pathology

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Proinflammatory CD20 + T cells contribute to CNS-directed autoimmunity

Cited by 42 publications

References 47 publications

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis

Timing of SARS-CoV-2 Vaccination Matters in People With Multiple Sclerosis on Pulsed Anti-CD20 Treatment

CD20+ T cells: an emerging T cell subset in human pathology

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Proinflammatory CD20 ⁺ T cells contribute to CNS-directed autoimmunity