RhoB blockade selectively inhibits autoantibody production in autoimmune models of rheumatoid arthritis and lupus.

ABSTRACT: During the development of autoimmune disease, a switch occurs in the antibody repertoire of B cells so that the production of pathogenic rather than non-pathogenic autoantibodies is enabled. However, there is limited knowledge concerning how this pivotal step occurs. Here, we present genetic and pharmacological evidence of a positive modifier function for the vesicular small GTPase RhoB in specifically mediating the generation of pathogenic autoantibodies and disease progression in the K/BxN preclinical mouse model of inflammatory arthritis. Genetic deletion of RhoB abolished the production of pathogenic autoantibodies and ablated joint inflammation in the model. Similarly, administration of a novel RhoB-targeted monoclonal antibody was sufficient to ablate autoantibody production and join

SUBMITTER: Mandik-Nayak L 

PROVIDER: S-EPMC5719251 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature