Plasma kinetics of complement component C4: comparison of three models.

Plasma C4 kinetics were studied in members of a kindred with hereditary incomplete C4 deficiency and in control subjects. Test subjects received iodine 125-labeled C4 intravenously, and plasma disappearance curves for 125I-C4 were plotted. By nonlinear least-squares analysis, we fit two-, three-, and four-exponential models of plasma disappearance to the plasma curves of each subject. Goodness of fit was significantly better for all subjects with the three-exponential versus the two-exponential model (p less than 0.0005). No further improvement in curve fit was accomplished by using a four-exponential model (p greater than 0.5). Metabolic rates and extravascular/plasma ratios calculated from the two- and three-exponential models were significantly different. As judged by extravascular/plasma ratio, the two-exponential model underestimated the amount of extravascular C4. Furthermore, the two-exponential model significantly over-estimated catabolic and synthetic rates. Hence, our results show that C4 kinetics are not optimally described by a conventional, two-exponential model. A possible explanation for our findings is that in previous studies of C4 metabolism, the analysis of plasma radioactivity disappearance curves was done by inspection, whereas we used least-squares analysis, a method that determines the number of exponentials with greater reliability.