Mechanism of action of an inhibitor of complement-mediated prevention of immune precipitation.
Glycoprotein 60 (gp60) is a normal plasma protein (mean concentration in normal serum 34 micrograms/ml) that is present in increased levels (mean concentration 97 micrograms/ml) in the sera of patients with rheumatoid arthritis (RA). Purified gp60 binds to IgG but not to IgM, and competitively inhibits the binding of C1q. In fluid-phase studies, purified gp60 was shown to reduce immune complex-mediated complement activation in a dose-dependent manner. The addition of Fab anti-gp60 to normal serum was associated with (i) increased levels of complement-mediated prevention of immune precipitation (PIP); (ii) increased total haemolytic complement activity when EAIgG, but not when EAIgM, were used as targets; and (iii) increased immune complex-mediated complement activation. Thus gp60 appears to regulate immune complex-mediated classical pathway activation. The findings that Fab anti-gp60 (i) only partly restored PIP in RA sera showing reduced PIP levels and (ii) only partly reduced inhibition of PIP by RA sera, show that gp60 is not entirely responsible for these abnormalities.
Ahmed
A E
AE
University of Glasgow, Department of Pathology, Western Infirmary, U.K.
Veitch
J
J
Whaley
K
K
D000936:Antigen-Antibody Complex / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001667:Binding, Competitive / Q000276:immunology; D001798:Blood Proteins / Q000494:pharmacology*; D011232:Chemical Precipitation; D003167:Complement Activation / Q000187:drug effects*; D015922:Complement C1q / Q000276:immunology; D003171:Complement Pathway, Classical / Q000187:drug effects*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008297:Male
D000936:Antigen-Antibody Complex; D001798:Blood Proteins; D006023:Glycoproteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015922:Complement C1q