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Review
. 2021 Jan;89(1):13-23.
doi: 10.1002/ana.25927. Epub 2020 Nov 4.

Role of B Cells in Multiple Sclerosis and Related Disorders

Giancarlo Comi  1 , Amit Bar-Or  2 , Hans Lassmann  3 , Antonio Uccelli  4 , Hans-Peter Hartung  5 , Xavier Montalban  6 , Per Solberg Sørensen  7 , Reinhard Hohlfeld  8 , Stephen L Hauser  9 ; Expert Panel of the 27th Annual Meeting of the European Charcot Foundation
Affiliations
Review

Role of B Cells in Multiple Sclerosis and Related Disorders

Giancarlo Comi et al. Ann Neurol. 2021 Jan.

Abstract

The success of clinical trials of selective B-cell depletion in patients with relapsing multiple sclerosis (MS) and primary progressive MS has led to a conceptual shift in the understanding of MS pathogenesis, away from the classical model in which T cells were the sole central actors and toward a more complex paradigm with B cells having an essential role in both the inflammatory and neurodegenerative components of the disease process. The role of B cells in MS was selected as the topic of the 27th Annual Meeting of the European Charcot Foundation. Results of the meeting are presented in this concise review, which recaps current concepts underlying the biology and therapeutic rationale behind B-cell-directed therapeutics in MS, and proposes strategies to optimize the use of existing anti-B-cell treatments and provide future directions for research in this area. ANN NEUROL 2021;89:13-23.

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Conflict of interest statement

POTENTIAL CONFLICT OF INTEREST

The following companies are involved in MS drug development: Actelion (Ac), Alexion (Al), Annexon (An), Atara Bio (AB), Bayer (Ba), Biogen (Bi), Bionure (Bn), Celgene/BMS (Ce), Forward Pharma (FP), GeNeuro (GN), GlaxoSmithKline (GS), Janssen/Johnson-Johnson (JJ), MedDay Pharmaceuticals (MP), Merck (Me), Molecular Stethoscope (Mo), NervGen (NG), Neurona Therapeutics (Ne), Novartis (No), Octapharma (Oa), Roche/Genentech (Ro), Sanofi/Genzyme (Sa), Teva (Te), TG Therapeutics (TG) and Viela Bio (VB).

GC has received personal compensation for consulting and speaking fees from No, Te, Sa, Me, Ce, Bi, Ro, FP, MP and Excemed.

ABO has served on scientific advisory boards for AB, Bi, Ce, JJ, Me, No, Ro and Sa, and has sponsored research agreements with Bi, Me, No and Ro.

HL received honoraria for lectures from No, Bi, Sa, Me. Ro and MP.

AU has received consultancy fees from Bi, SG, Me, No, Ro and Te and research support from Bi, Me and No.

HPH received fees for serving on steering committees, data monitoring committees and scientific advisory boards from Ba, Bi, Ce, GN, Me, No, Oa, Ro, Sa, Te, TG, VB with approval by the Rector of Heinrich-Heine-University.

XM received speaking honoraria and travel expenses for scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past 3 years with Ac, Al, Ba, Bi, Ce, Me, Excemed, Sa, MP, Multiple Sclerosis International Federation, NG, National Multiple Sclerosis Society, No, Ro, Te and TG.

PSS has received personal compensation for serving on scientific advisory boards, steering committees, independent data monitoring committees or speaker honoraria for Bi, Me, No, Te, GS and Ce.

RH received honoraria and grant support from No, Sa, Bi, Te, Me, JJ and Ro.

SLH currently serves on the Scientific Advisory Board of Symbiotix, An, Bn, and Mo and on the Board of Trustees of Ne. SLH also has received travel reimbursement and writing assistance from Ro and No for CD20-related meetings and presentations.

Figures

FIGURE 1.
FIGURE 1.. ANTI-CD20 MONOCLONAL ANTIBODIES: MECHANISMS OF ACTION AND MATURATION STAGES.
Abbreviations - ADCC: antibody-dependent cell-mediated toxicity; APC: antigen-presenting cell; BCR: B cell receptor; CDC: complement-dependent cytotoxicity; CSF: cerebrospinal fluid; DAMP: damage-associated molecular pattern molecule; GM-CSF: granulocyte macrophage-colony stimulating factor; IL: interleukin; mAb: monoclonal antibody; MHC: major histocompatibility complex; LT- α: lymphotoxin-α; PAMP: pathogen-associated molecular pattern molecule; TCR: T cell receptor; TLR: toll-like receptor; TNF-α: tumour-necrosis factor-alpha
See this image and copyright information in PMC

References

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