Rituximab abrogates aquaporin-4-specific germinal center activity in patients with neuromyelitis optica spectrum disorders.

Damato V., Theorell J., Al-Diwani A., Kienzler A-K., Makuch M., Sun B., Handel A., Akdeniz D., Berretta A., Ramanathan S., Fower A., Whittam D., Gibbons E., McGlashan N., Green E., Huda S., Woodhall M., Palace J., Sheerin F., Waters P., Leite MI., Jacob A., Irani SR.

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.

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

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