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SignificanceBy studying paired blood and deep cervical lymph node samples from patients with neuromyelitis optica spectrum disorders, our data provide evidence for a germinal center-based generation of aquaporin-4 antibodies. Frequent serum aquaporin-4 immunoglobulin Ms (IgMs) and shifts in IgG subclasses were observed alongside preferential synthesis of aquaporin-4 IgGs and aquaporin-4-reactive B cells within lymph nodes. Both intranodal synthesis of aquaporin-4 antibodies and intranodal aquaporin-4-reactive B cells were robustly eliminated with rituximab administration. This study systematically explores lymph nodes that drain the central nervous system (CNS) in patients with CNS autoimmunity and offers a potential explanation as to why rituximab is clinically highly efficacious in autoantibody-mediated diseases despite no accompanying reduction in serum autoantibody levels.

Original publication

DOI

10.1073/pnas.2121804119

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

14/06/2022

Volume

119

Keywords

aquaporin, autoimmunity, cervical lymph nodes, neuromyelitis optica, rituximab, Aquaporin 4, Autoantibodies, Germinal Center, Humans, Neuromyelitis Optica, Rituximab