Pathology

Autoimmunity

Rituximab

Neuromyelitis optica

Engineering

Aquaporin 4

Antibody

Autoantibody

Aquaporin 1

Inlet

Immunology

Water channel

Lymph node

B cell

Lymph

Germinal center

Medicine

Mechanical engineering

Proceedings of the National Academy of Sciences

Significance By 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.

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