<scp>CD20</scp><sup>+</sup> T Cells as Pathogenic Players and Therapeutic Targets in <scp>MS</scp>

Meinl, Edgar; Hohlfeld, Reinhard

doi:10.1002/ana.26232

Cited by 4 publications

(4 citation statements)

References 15 publications

(76 reference statements)

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“…However, long-lived antibody-producing plasma cells are CD20 negative [32]. Notably, CD20 is not exclusive to B cells but is also present on a subset of T cells that could play a role in the pathogenesis of MS [33]. Several anti-CD20 therapeutic monoclonal antibodies were developed to achieve B-cell depletion.…”

Section: T Cells Versus B Cellsmentioning

confidence: 99%

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Antibody Therapies for Progressive Multiple Sclerosis and for Promoting Repair

Havla

Hohlfeld

2022

Neurotherapeutics

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Progressive multiple sclerosis (PMS) is clinically distinct from relapsing–remitting MS (RRMS). In PMS, clinical disability progression occurs independently of relapse activity. Furthermore, there is increasing evidence that the pathological mechanisms of PMS and RRMS are different. Current therapeutic options for the treatment of PMS remain inadequate, although ocrelizumab, a B-cell-depleting antibody, is now available as the first approved therapeutic option for primary progressive MS. Recent advances in understanding the pathophysiology of PMS provide hope for new innovative therapeutic options: these include antibody therapies with anti-inflammatory, neuroprotective, and/or remyelination-fostering effects. In this review, we summarize the relevant trial data relating to antibody therapy and consider future antibody options for treating PMS.

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Section: T Cells Versus B Cellsmentioning

confidence: 99%

“…twice yearly for the treatment of PPMS with evidence of disease activity in March 2017 (FDA) and January 2018 (EMA). The antibody targets CD20-expressing lymphocytes, mostly B cells but also a smaller subset of T cells [32,33].…”

Section: Ocrelizumabmentioning

confidence: 99%

Antibody Therapies for Progressive Multiple Sclerosis and for Promoting Repair

Havla

Hohlfeld

2022

Neurotherapeutics

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“…Anti-CD20 mAbs are highly efficient in treating relapsingremitting multiple sclerosis (MS), and the anti-CD20 mAb ocrelizumab is the first approved treatment that slows disability progression in primary progressive MS. 1,2 Anti-CD20 treatment largely depletes circulating B cells and a subset of CD20 + T cells. [1][2][3][4][5][6][7] In contrast to the almost complete depletion of CD20 + cells in blood, there is evidence that CD20 + B cells in the lymphatic organs and the inflamed CNS are not eliminated to the same extent during anti-CD20 treatment. 8,9 Furthermore, CD20 − plasma cells persist in their survival niches in the bone marrow and the inflamed CNS, 1 and the generation of mucosal IgA + plasmablasts continues despite anti-CD20 treatment.…”

mentioning

confidence: 99%

“…Anti-CD20 mAbs are highly efficient in treating relapsing-remitting multiple sclerosis (MS), and the anti-CD20 mAb ocrelizumab is the first approved treatment that slows disability progression in primary progressive MS. 1,2 Anti-CD20 treatment largely depletes circulating B cells and a subset of CD20 + T cells. 1-7…”

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confidence: 99%

Ocrelizumab Treatment Modulates B-Cell Regulating Factors in Multiple Sclerosis

Oswald

Wong

et al. 2023

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesAntibodies to CD20 efficiently reduce new relapses in multiple sclerosis (MS), and ocrelizumab has been shown to be effective also in primary progressive MS. Although anti-CD20 treatments efficiently deplete B cells in blood, some B cells and CD20−plasma cells persist in lymphatic organs and the inflamed CNS; their survival is regulated by the B cell–activating factor (BAFF)/A proliferation-inducing ligand (APRIL) system. The administration of a soluble receptor for BAFF and APRIL, atacicept, unexpectedly worsened MS. Here, we explored the long-term effects of ocrelizumab on immune cell subsets as well as on cytokines and endogenous soluble receptors comprising the BAFF-APRIL system.MethodsWe analyzed immune cell subsets and B cell–regulating factors longitudinally for up to 2.5 years in patients with MS treated with ocrelizumab. In a second cohort, we determined B-cell regulatory factors in the CSF before and after ocrelizumab. We quantified the cytokines BAFF and APRIL along with their endogenous soluble receptors soluble B-cell maturation antigen (sBCMA) and soluble transmembrane activator and calcium-modulator and cyclophilin ligand (CAML) interactor (sTACI) using enzyme-linked immunosorbent assays (ELISAs). In addition, we established an in-house ELISA to measure sTACI-BAFF complexes.ResultsOcrelizumab treatment of people with MS persistently depleted B cells and CD20+T cells. This treatment enhanced BAFF and reduced the free endogenous soluble receptor and decoy sTACI in both serum and CSF. Levels of sTACI negatively correlated with BAFF levels. Reduction of sTACI was associated with formation of sTACI-BAFF complexes.DiscussionWe describe a novel effect of anti-CD20 therapy on the BAFF-APRIL system, namely reduction of sTACI. Because sTACI is a decoy for APRIL, its reduction may enhance local APRIL activity, thereby promoting regulatory IgA+plasma cells and astrocytic interleukin (IL)-10 production. Thus, reducing sTACI might contribute to the beneficial effect of anti-CD20 as exogenous sTACI (atacicept) worsened MS.Classification of EvidenceThis study provides Class IV evidence that endogenous sTACI in blood and CSF is decreased after ocrelizumab treatment.

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