Molecular Level Characterization of Circulating Aquaporin-4 Antibodies in Neuromyelitis Optica Spectrum Disorder

Jie Li, Sam A. Bazzi, Florian Schmitz, Hidetaka Tanno, Jonathan R. McDaniel, Chang Han Lee, Chaitanya Joshi, Jin Eyun Kim, Nancy Monson, Benjamin M. Greenberg, Kristina Hedfalk, Esther Melamed, Gregory C. Ippolito

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


ObjectiveTo determine whether distinct aquaporin-4 (AQP4)-IgG lineages play a role in neuromyelitis optica spectrum disorder (NMOSD) pathogenesis, we profiled the AQP4-IgG polyclonal serum repertoire and identified, quantified, and functionally characterized distinct AQP4-IgG lineages circulating in 2 patients with NMOSD.MethodsWe combined high-Throughput sequencing and quantitative immunoproteomics to simultaneously determine the constituents of both the B-cell receptor (BCR) and the serologic (IgG) anti-AQP4 antibody repertoires in the peripheral blood of patients with NMOSD. The monoclonal antibodies identified by this platform were recombinantly expressed and functionally characterized in vitro.ResultsMultiple antibody lineages comprise serum AQP4-IgG repertoires. Their distribution, however, can be strikingly different in polarization (polyclonal vs pauciclonal). Among the 4 serum AQP4-IgG monoclonal antibodies we identified in 2 patients, 3 induced complement-dependent cytotoxicity in a model mammalian cell line (p < 0.01).ConclusionsThe composition and polarization of AQP4-IgG antibody repertoires may play an important role in NMOSD pathogenesis and clinical presentation. Here, we present a means of coupling both cellular (BCR) and serologic (IgG) antibody repertoire analysis, which has not previously been performed in NMOSD. Our analysis could be applied in the future to clinical management of patients with NMOSD to monitor disease activity over time as well as applied to other autoimmune diseases to facilitate a deeper understanding of disease pathogenesis relative to autoantibody clones.

Original languageEnglish (US)
Article numbere1034
JournalNeurology: Neuroimmunology and NeuroInflammation
Issue number5
StatePublished - Sep 24 2021

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


Dive into the research topics of 'Molecular Level Characterization of Circulating Aquaporin-4 Antibodies in Neuromyelitis Optica Spectrum Disorder'. Together they form a unique fingerprint.

Cite this