Synovial fluid expression of autoantibodies specific for RAGE relates to less erosive course of rheumatoid arthritis.
OBJECTIVE
The receptor for advanced glycation end products (RAGE) is expressed by many cells in joints of rheumatoid arthritis (RA) patients and interacts with a variety of pro-inflammatory ligands that are enriched in inflamed joint. The RAGE-ligand interaction leads to a sustained inflammatory response. Also, secreted form of the receptor, called soluble RAGE (sRAGE), the levels of which are decreased in RA patients, modulates inflammatory responses. We sought to determine whether RA patients display increased occurrence of autoantibodies against RAGE and whether such an autoantibody production is related to disease characteristics.


METHODS
Matching samples of blood and synovial fluid were collected from 50 patients with RA with acute joint effusion. Blood from 43 healthy individuals and synovial fluid samples from 32 patients with non-inflammatory joint diseases were used for comparison. Anti-RAGE antibody levels were analysed using an ELISA.


RESULTS
RA patients displayed significantly higher blood and synovial fluid levels of anti-RAGE antibodies, both of IgG as well as of IgM class as compared with healthy controls and with patients with non-inflammatory joint diseases. Patients with seropositive RA had significantly less IgG antibodies in their synovial fluid as compared to seronegative patients. Furthermore, the presence of IgG class of anti-RAGE antibodies locally in the joint was found to be related to less aggressive, i.e. non-erosive disease.


CONCLUSIONS
These results suggest that RAGE-specific B cell response protect patients with RA from destructive course of the disease.
Pullerits
R
R
Department of Rheumatology and Inflammation Research, University of Göteborg, Göteborgrille, Sweden. pullerits@rheuma.gu.se
Bokarewa
M
M
Dahlberg
L
L
Tarkowski
A
A
D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis* / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D007075:Immunoglobulin M / Q000032:analysis / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis / Q000276:immunology*; D012217:Rheumatoid Factor / Q000032:analysis; D012995:Solubility; D013582:Synovial Fluid / Q000276:immunology*
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D012217:Rheumatoid Factor; D008727:Methotrexate