B cells are a central driver of the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD)1
Role of B cells in NMSOD

ROLE OF B CELLS IN NMOSD

B cells play a fundamental role in NMOSD immunopathology with multiple proposed mechanisms contributing to disease pathogenesis.1

AQP4-IgG Production

AQP4-IgG production

Plasmablasts and plasma cells secrete autoantibodies that traverse the blood-brain barrier and initiate central nervous system (CNS) damage.1

enhanced proinflammatory activity

Enhanced proinflammatory activity

Plasmablasts secrete cytokines that facilitate neutrophil and macrophage infiltration of the CNS.1

diminished B-cell regulatory function

Diminished B-cell regulatory function

The loss of B-cell populations suppresses proinflammatory T-cell activity.1

Adapted from Bennett JL et al. 2015.1

B cells are a central therapeutic target for disease-modifying treatments in NMOSD.1

CD19 AS A TARGET

CD19 is a specific marker of B cells which, unlike CD20, also marks antibody-secreting B cells.2

  • In patients with NMOSD, CD19+ plasmablasts are elevated in circulation3
  • During an NMOSD attack, these cells are further increased3

CD19 is broadly expressed across every stage of the B-cell lineage, including on plasmablasts and some plasma cells.1,2 CD20 is not expressed on AQP4-IgG-secreting plasmablasts and plasma cells. Therefore, CD20-targeting therapies may not have a direct depleting effect on these cell populations.2

process of cells expressing CD19 and CD20

Adapted from Siebert N et al. 2021.6

Targeting CD19 offers a therapeutic strategy that addresses a pathogenic driver central to NMOSD.1,2

UPLIZNA selectively binds to CD19, resulting in antibody-dependent targeted B-cell depletion. Although the exact mechanism of action is not fully understood, B-cell depletion leads to reduced AQP4-antibody concentrations, which may downregulate the subsequent complement activation cascade early on.4

AQP4-IgG-antibody-dependent activation of the complement system1

AGP4-igG-antibody-dependent activation of the complement system

ADCC: antibody-dependent cellular cytolysis; AQP4-IgG: aquaporin-4 immunoglobulin G; BBB: blood-brain barrier; C5: complement component 5; CD19+: Cluster of Differentiation 19-positive; CDC: complement-dependent cytotoxicity; CNS: central nervous system; IL: interleukin; NMOSD: neuromyelitis optica spectrum disorder.

Mechanism of Action

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Support & Resources

Pre- and during-UPLIZNA treatment information

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Summary of Product Characteristics

  1. Bennett JL, O’Connor KC, Bar-Or A, et al. B lymphocytes in neuromyelitis optica. Neurol Neuroimmunol Neuroinflamm. 2015;2(3):e104. doi:10.1212/ NXI.0000000000000104.
  2. Forsthuber TG, Cimbora DM, Ratchford JN, et al. B cell-based therapies in CNS autoimmunity: differentiating CD19 and CD20 as therapeutic targets. Ther Adv Neurol Disord. 2018;11:1-13. doi:10.1177/1756286418761697.
  3. Chihara N, Aranami T, Sato W, et al. Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proc Natl Acad Sci U S A. 2011;108(9):3701-3706. doi:10.1073/pnas.1017385108.
  4. Herbst R, Wang Y, Gallagher S, et al. B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody. J Pharmacol Exp Ther. 2010;335:213-222. doi: 10.1124/jpet.110.168062
  5. Prasad S, Chen J. What you need to know about AQP4, MOG, and NMOSD. Semin Neurol. 2019;39(6):718-731. doi:10.1055/s-0039-3399505.
  6. Siebert N, Duchow A, Paul F, et al. Inebilizumab in AQP4-Ab-positive neuromyelitis optica spectrum disorder. Drugs Today (Barc). 2021 May;57(5):321-336. doi: 10.1358/dot.2021.57.5.3265453.