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.
Magnusson
Sofia E
SE
Department of Cell and Molecular Biology, Program for Molecular Immunology, Biomedical Centre, Uppsala University, Box 596, Husargatan 3, SE-751 24 Uppsala, Sweden.
Andrén
Maria
M
Nilsson
Kajsa E
KE
Sondermann
Peter
P
Jacob
Uwe
U
Kleinau
Sandra
S
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005528:Foot / Q000473:pathology; D006651:Histocytochemistry; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D017452:Receptors, IgG / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012260:Ribonucleases / Q000737:chemistry
D016207:Cytokines; C499173:FCGR2B protein, human; D007074:Immunoglobulin G; D012333:RNA, Messenger; D017452:Receptors, IgG; D011994:Recombinant Proteins; D012260:Ribonucleases