Delivery of an mi R155 inhibitor by anti- CD20 single-chain antibody into B cells reduces the acetylcholine receptor-specific autoantibodies and ameliorates experimental autoimmune myasthenia gravis.

MicroRNA-155 (mi R155) is required for antibody production after vaccination with attenuated Salmonella. mi R155-deficient B cells generated reduced germinal centre responses and failed to produce high-affinity immunoglobulin ( Ig)G1 antibodies. In this study, we observed up-regulation of mi R155 in the peripheral blood mononuclear cells ( PBMCs) of patients with myasthenia gravis ( MG), and mi R155 was also up-regulated in torpedo acetylcholine receptor ( T- AChR)-stimulated B cells. We used an inhibitor of mi R155 conjugated to anti- CD20 single-chain antibody to treat both the cultured B cells and the experimental autoimmune MG ( EAMG) mice. Our results demonstrated that silencing of mi R155 by its inhibitor impaired the B cell-activating factor ( BAFF)- R-related signalling pathway and reduced the translocation of nuclear factor ( NF)-κ B into the nucleus. Additionally, AChR-specific autoantibodies were reduced, which may be related to the altered amounts of marginal zone B cells and memory B cells in the spleens of EAMG mice. Our study suggests that mi R155 may be a promising target for the clinical therapy of MG. [ABSTRACT FROM AUTHOR]