AQP4 autoantibody production in plasmablasts and plasma cells drives the pathophysiology of NMOSD1,2

AQP4 is a primary target of attack in B-cell–driven immune dysregulation1,3

The Pathophysiology of NMOSD

AQP4

0:24

Pathways to Damage

1:03

Complement Dependent

1:24

ADCC

1:42

B Cell – T Cell Interplay

2:12
The Pathophysiology of NMOSD
  • AQP4 is a water channel protein expressed in astrocytes in the CNS, predominantly in the brain, spinal cord, and optic nerve3
  • AQP4 autoantibodies mediate astrocyte destruction via complement-dependent and -independent mechanisms, leading to widespread damage in surrounding tissues4

The immunopathogenesis of NMOSD is multifaceted1:

  • Autoantibody production
  • Cytokine secretion
  • Antigen presentation
  • T-cell interactions

CD19 as a target of therapy

CD19 is expressed broadly across the B-cell lineage but is not expressed by T cells, making it an important therapeutic target in NMOSD2,5,6

Table showing CD19 expression across the B-cell lineage Table showing CD19 expression across the B-cell lineage Table showing CD19 expression across the B-cell lineage

Learn how to differentiate
NMOSD from MS Symptoms and MRI

NMOSD, neuromyelitis optica spectrum disorder.

  1. Bennett JL, O’Connor KC, Bar-or A, et al. B lymphocytes in neuromyelitis optica. Neurology. 2015;2:1-11. doi:10.1212/NXI.0000000000000104
  2. Fortshuber TG, Cimbora TM, 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. Papadopolous MC, Verkman AS. Aquaporin 4 and neuromyelitis optica. Lancet Neurol. 2012;11(6):535-544. doi:10.1016/S1474-4422(12)70133-3
  4. Duan T, Smith AJ, Verkman AS. Complement-independent bystander injury in AQP4-IgG seropositive neuromyelitis optica produced by antibody-dependent cellular cytotoxicity. Acta Neuropathol Commun. 2019;7:1-16. doi:10.1186/s40478-019-0766-7
  5. Baker D, Marta M, Pryce G, Giovannoni G, Schmierer K. Memory B cells are major targets for effective immunotherapy in relapsing multiple sclerosis. EBioMedicine. 2017;16:41-50.
  6. Ho JWK, Koundinya R, Caetano TS, et al. Inferring differential leukocyte activity from antibody microarrays using a latent variable model. Genom Inform. 2008;21:126-137