CD19 as a therapeutic target in a spontaneous autoimmune polyneuropathy.

Autor(es): Abraham P M,Quan S H,Dukala D,Soliven B

Resumo: Spontaneous autoimmune polyneuropathy (SAP) in B7-2 knock-out non-obese diabetic (NOD) mice is mediated by myelin protein zero (P0)-reactive T helper type 1 (Th1) cells. In this study, we investigated the role of B cells in SAP, focusing on CD19 as a potential therapeutic target. We found that P0-specific plasmablasts and B cells were increased in spleens of SAP mice compared to wild-type NOD mice. Depletion of B cells and plasmablasts with anti-CD19 monoclonal antibody (mAb) led to attenuation of disease severity when administered at 5 months of age. This was accompanied by decreased serum immunoglobulin (Ig)G and IgM levels, depletion of P0-specific plasmablasts and B cells, down-regulation/internalization of surface CD19 and increased frequency of CD4(+) regulatory T cells in spleens. We conclude that B cells are crucial to the pathogenesis of SAP, and that CD19 is a promising B cell target for the development of disease-modifying agents in autoimmune neuropathies.

Palavras-Chave: B cells, CIDP, Guillain-Barré syndrome, autoimmunity, co-stimulatory molecules

Imprenta: Clinical and Experimental Immunology, v. 175, n. 2, p. 181-191, 2014

Identificador do objeto digital: 10.1111/cei.12215

Descritores: Guillain-Barre Syndrome - Biosynthesis ; Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Antibodies ; Guillain-Barre Syndrome - Autoimmunity ; Guillain-Barre Syndrome - Immunology

Data de publicação: 2014