Determination of serum levels of complement component C4b-binding protein: influence of age and inflammation.
C4b-binding protein (C4b-BP) is a high molecular weight plasma protein which inhibits the activity of the classical complement pathway C3 convertase. In addition to multiple binding sites for C4b, C4b-BP possesses a single binding site for vitamin K-dependent protein S, an inhibitor of blood coagulation. As protein S bound to C4b-BP has no anticoagulant activity, C4b-BP participates in the regulation of both the complement and the coagulation pathways. We have produced and immunochemically characterized a series of murine monoclonal antibodies to human C4b-BP. A mixture of four monoclonal antibodies precipitating C4b-BP both in agarose gel and in solution was used to develop a highly reproducible radial immunodiffusion method for the measurement of C4b-BP in human serum. C4b-BP levels were measured in sera from 284 patients referred to our central laboratory. Samples from subjects with an increased erythrocyte sedimentation rate (ESR), a1-acid glycoprotein (a1-AGP) or C-reactive protein (CRP) had significantly higher C4b-BP levels (307 mg/l, 292-322 mg/l, geometric mean and 95% confidence limits of the mean) than those from subjects without elevation of the aforementioned established acute phase reactants (231 mg/l, 226-237 mg/l, P less than 0.00001). C4b-BP was significantly (P less than 0.001) correlated with ESR (r = 0.715), a1-AGP (r = 0.692) and CRP (r = 0.567). There was no gender-related difference in C4b-BP levels. In subjects with no increased acute phase reactants there was a significant correlation between C4b-BP levels and age (r = 0.387, P less than 0.001). High C4b-BP might contribute to the increased thrombotic risk associated with inflammation and aging.
Marcovina
S M
SM
Department of Medicine, University of Washington, Seattle 98103.
Zoppo
A
A
Viganó-D'Angelo
S
S
Di Cola
G
G
D'Angelo
A
A
D000328:Adult; D000367:Age Factors; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis* / Q000276:immunology; D015935:Complement C4b / Q000378:metabolism*; D003169:Complement Inactivator Proteins; D005260:Female; D006023:Glycoproteins; D006801:Humans; D005779:Immunodiffusion; D007074:Immunoglobulin G / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D007249:Inflammation / Q000097:blood*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009961:Orosomucoid / Q000032:analysis; D011951:Receptors, Complement / Q000032:analysis* / Q000276:immunology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D009961:Orosomucoid; D011951:Receptors, Complement; D015935:Complement C4b; D002097:C-Reactive Protein