Consumption of C4b-binding protein (C4BP) during in vivo activation of theclassical complement pathway

C4BP has a central role in regulating the classical complement (C') pathway , but it is still uncertain whether or not it is consumed during in vivo co mplement activation. Attempts to demonstrate changes in C4BP plasma levels in systemic lupus erythematosus and essential mixed cryoglobulinaemia have failed, probably due to up-regulation of this protein during the inflammato ry reaction. We have studied one patient with severe post-transfusion compl ement-mediated anaphylaxis (CMA), and 67 patients with hereditary C1 inhibi tor deficiency (hereditary angioedema (HAE)). The first of these two condit ions is characterized by the absence of systemic inflammatory reaction and the second by acute and chronic activation of the C' classical pathway. C4B P, C4BP-C4b complex, and soluble terminal C' complex (sC5b-9) were measured in the patients' plasmas by ELISA techniques and C3a and C4a by radioimmun oassays. In CMA, 15 min after the transfusion, there was a massive C' activ ation, with increases in C4a, C3a, sC5b-9, C4BP-C4b complexes and decreases in C4, C3 and C4BP. All parameters reverted to preinfusion values within 2 4 h. Depletion of C4 was correlated with that of C4BP. In patients with HAE , the median value of C4BP (83% range 54-165) was significantly lower (P < 0.0001) than in normal controls (99% range 70-159), with no difference betw een patients in remission or during acute attacks. C4BP-C4b complexes could not be detected in HAE patients. The results of this study indicate that C 4BP is consumed in vivo during acute, and possibly during chronic activatio n of the C' classical pathway, and that this protein, after interaction wit h C4b, not longer circulates in plasma.