Synovial fluid levels of complement SC5b-9 and fragment Bb are elevated in patients with rheumatoid arthritis.
To determine whether complement turnover in synovial fluids of patients with rheumatoid arthritis (RA) reflects activation by the classical or alternative pathway, we used novel immunoassays to measure products of complement activation (the membrane attack complex SC5b-9 and the cleavage fragments Bb and C4d). Mean synovial fluid levels of SC5b-9 were more than 8 times higher in RA than in crystal-induced arthritis (gout and pseudogout) and over 16 times higher than in degenerative joint disease (DJD). Similarly, Bb levels were more than 3 times higher in RA synovial fluids than in crystal-induced arthritis and over 7 times higher than in DJD. Levels of C4d did not differ among the groups. SC5b-9 levels correlated with synovial fluid C3 anaphylatoxin (C3a), Bb, and C4d levels (r = 0.81, 0.62, and 0.51, respectively). In patients with RA, synovial fluid SC5b-9 levels correlated with C3a and Bb (r = 0.6 and 0.56, respectively) but not with C4d. Therefore, novel assays for complement activation indicate that both classical and alternative pathways are involved in complement turnover and that the alternative pathway contributes more to complement activation in RA than in DJD or crystal-induced arthritis.
Brodeur
J P
JP
Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0263.
Ruddy
S
S
Schwartz
L B
LB
Moxley
G
G
D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D003167:Complement Activation; D051561:Complement C3 Convertase, Alternative Pathway; D003179:Complement C3b / Q000032:analysis* / Q000378:metabolism; D003181:Complement C4 / Q000032:analysis / Q000378:metabolism; D015935:Complement C4b; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000032:analysis*; D006073:Gout / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007592:Joint Diseases / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000032:analysis* / Q000378:metabolism; D013582:Synovial Fluid / Q000737:chemistry* / Q000378:metabolism
D003181:Complement C4; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D010446:Peptide Fragments; C047610:SC5b-9 protein complex; D003179:Complement C3b; D015935:Complement C4b; C032261:complement C4d; D003165:Complement System Proteins; D051561:Complement C3 Convertase, Alternative Pathway