Compounds Suppress Arthritis Development in Mice
Compounds block binding of immune complexes
WEDNESDAY, Nov. 26 (HealthDay News) -- Compounds that block the binding of immune complexes can effectively block the development and progression of arthritis in mice, according to a study published online Nov. 25 in Immunology & Cell Biology.
Geoffrey A. Pietersz, Ph.D., from the Burnet Institute at Austin in Heidelberg, Victoria, Australia, and colleagues used the three-dimensional structure of the human Fc receptor FcγRIIa, which binds antibody-antigen complexes and has been implicated in autoimmune inflammation, to design small molecule inhibitors that block binding of the immune complexes.
The researchers found inhibitors that could block processes induced by immune complex binding, including platelet activation and aggregation and tumor necrosis factor secretion from macrophages. In mice carrying the human FcγRIIa gene and induced to develop arthritis, the compounds strongly suppressed arthritis development and progression. The compounds were more effective than methotrexate and anti-CD3 antibody in suppressing arthritis over the long term, according to the study.
"Thus, in vitro and in vivo activity of these small chemical entity FcγRIIa receptor antagonists demonstrated their potential as anti-inflammatory agents for autoimmune diseases involving immune complexes," Pietersz and colleagues conclude.