Amelioration of collagen-induced arthritis by human recombinant soluble FcgammaRIIb

Immune complex (IC) binding to Fc gamma receptors (FcgammaRs) is central for inflammatory reactions seen in autoimmune diseases. Consequently, a therapeutic agent with a possibility to interfere with binding of pathogenic IC to FcgammaRs would be valuable in autoimmune disorders such as rheumatoid arthritis (RA). Here we have explored the therapeutic effect of a recombinant soluble human FcgammaRIIb (sFcgammaRIIb) protein in collagen-induced arthritis (CIA). In vitro studies of the sFcgammaRIIb demonstrated binding to mouse IgG, suggesting that sFcgammaRIIb can absorb pathogenic IgG anti-collagen type II (CII) IC in vivo. Hence, administration of sFcgammaRIIb significantly reduced CIA severity compared to control treated mice. The sFcgammaRIIb treated mice had significantly less IgG anti-CII antibodies in serum and lower mRNA levels of inflammatory cytokines compared to control mice. In conclusion, sFcgammaRIIb treatment ameliorates CIA by reducing IC-stimulated inflammation and joint swelling. This suggests that recombinant sFcgammaRIIb may be useful as therapeutic agent in RA.