High synovial expression of the inhibitory FcgammaRIIb in rheumatoid arthritis.
Activating Fc gamma receptors (FcgammaRs) have been identified as having important roles in the inflammatory joint reaction in rheumatoid arthritis (RA) and murine models of arthritis. However, the role of the inhibitory FcgammaRIIb in the regulation of the synovial inflammation in RA is less known. Here we have investigated synovial tissue from RA patients using a novel monoclonal antibody (GB3) specific for the FcgammaRIIb isoform. FcgammaRIIb was abundantly expressed in synovia of RA patients, in sharp contrast to the absence or weak staining of FcgammaRIIb in synovial biopsies from healthy volunteers. In addition, the expression of FcgammaRI, FcgammaRII and FcgammaRIII was analyzed in synovia obtained from early and late stages of RA. Compared with healthy synovia, which expressed FcgammaRII, FcgammaRIII but not FcgammaRI, all activating FcgammaRs were expressed and significantly up-regulated in RA, regardless of disease duration. Macrophages were one of the major cell types in the RA synovium expressing FcgammaRIIb and the activating FcgammaRs. Anti-inflammatory treatment with glucocorticoids reduced FcgammaR expression in arthritic joints, particularly that of FcgammaRI. This study demonstrates for the first time that RA patients do not fail to up-regulate FcgammaRIIb upon synovial inflammation, but suggests that the balance between expression of the inhibitory FcgammaRIIb and activating FcgammaRs may be in favour of the latter throughout the disease course. Anti-inflammatory drugs that target activating FcgammaRs may represent valuable therapeutics in this disease.
Magnusson
Sofia E
SE
Department of Cell and Molecular Biology, Programme for Molecular Immunology, Uppsala University, Husargatan 3, Uppsala, 751 24, Sweden.
Engström
Marianne
M
Jacob
Uwe
U
Ulfgren
Ann-Kristin
AK
Kleinau
Sandra
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000187:drug effects; D013583:Synovial Membrane / Q000378:metabolism*
D000911:Antibodies, Monoclonal; C489017:FCGR1A protein, human; C499173:FCGR2B protein, human; C496124:FCGR3A protein, human; D005938:Glucocorticoids; D017452:Receptors, IgG