Immunohistochemical determination of complement activation in joint tissues of patients with rheumatoid arthritis and osteoarthritis using neoantigen-specific monoclonal antibodies.
Murine monoclonal antibodies specific for neoepitopes expressed by C9 incorporated into membrane attack complexes and by membrane-bound C3b and iC3b have been prepared and characterised. These reagents were used to determine the extent and locus of complement activation in synovial-tissues obtained from patients with rheumatoid arthritis and osteoarthritis. In the four rheumatoid arthritis patients there was extensive deposition of C3 activation products and C5b-9 complexes onto the synovial membrane and the pattern of deposition of both neoantigens in serial tissue sections was very similar. There was less extensive staining for C3 and, particularly, C9 neoepitopes on the apical surface of vessel endothelia. In two of four osteoarthritic patients a similar pattern of C3 and C9 neoepitope deposition was found; in the remaining patients no C5b-9 could be located. Synovial vessel walls, but not synovial cells, from both groups of patients stained extensively for the complement regulatory protein CD59. In synovial membranes from patients with osteoarthritis, C9 appeared to be present predominantly in SC5b-9 complexes whereas in rheumatoid arthritis patients no evidence of S-protein incorporation into membrane attack complexes could be demonstrated, suggesting that in rheumatoid arthritis there is damage to the synovial membrane as a result of complement activation and C5b-9 deposition.
Kemp
P A
PA
Research and Preclinical Development, CIBA-Geigy Pharmaceuticals, West Sussex, UK.
Spragg
J H
JH
Brown
J C
JC
Morgan
B P
BP
Gunn
C A
CA
Taylor
P W
PW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D003167:Complement Activation; D003179:Complement C3b / Q000378:metabolism; D003186:Complement C9 / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D000939:Epitopes / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology*; D013583:Synovial Membrane / Q000276:immunology*
D000911:Antibodies, Monoclonal; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D000939:Epitopes; D003179:Complement C3b