CD97 neutralisation increases resistance to collagen-induced arthritis in mice.
Synovial tissue of rheumatoid arthritis (RA) patients is characterised by an influx and retention of CD97-positive inflammatory cells. The ligands of CD97, CD55, chondroitin sulfate B, and alpha5beta1 (very late antigen [VLA]-5) are expressed abundantly in the synovial tissue predominantly on fibroblast-like synoviocytes, endothelium, and extracellular matrix. Based upon this expression pattern, we hypothesise CD97 expression to result in accumulation of inflammatory cells in the synovial tissue of RA patients. To determine the therapeutic effect of blocking CD97 in an animal model of RA, collagen-induced arthritis was induced in a total of 124 DBA/J1 mice. Treatment was started on day 21 (early disease) or on day 35 (longstanding disease) with the blocking hamster anti-mouse CD97 monoclonal antibody (mAb) 1B2, control hamster immunoglobulin, or NaCl, applied intraperitoneally three times a week. The paws were evaluated for clinical signs of arthritis and, in addition, examined by radiological and histological analysis. Mice receiving 0.5 mg CD97 mAb starting from day 21 had significantly less arthritis activity and hind paw swelling. Furthermore, joint damage and inflammation were reduced and granulocyte infiltration was decreased. When treatment was started on day 35, CD97 mAb treatment had similar effects, albeit less pronounced. The results support the notion that CD97 contributes to synovial inflammation and joint destruction in arthritis.
Kop
Else N
EN
Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, P,O, Box 22700, 1100 DE Amsterdam, The Netherlands.
Adriaansen
Janik
J
Smeets
Tom J M
TJ
Vervoordeldonk
Margriet J
MJ
van Lier
René A W
RA
Hamann
Jörg
J
Tak
Paul P
PP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D007167:Immunotherapy / Q000379:methods*; D015850:Interleukin-6 / Q000097:blood; D007596:Joints / Q000276:immunology / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D043562:Receptors, G-Protein-Coupled; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
C490633:Adgre5 protein, mouse; D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled