| Comments |
P.503 right column bottom paragraph: "Determining the “physiologic” levels of complement peptides is problematic, with wide variations in the reported values (Table 1). This is due in part to the different assay techniques and in part to the nature of the biologic sample tested. Serum, obtained after clotting of plasma, generally contains higher levels of the fragments due to the actions of the proteases in the clotting cascade on C3, C4, and C5 (Amara et al., 2008) (see Section I.C). Thus, plasma is a more reliable indicator of circulating complement peptide levels, particularly where EDTA has been used, effectively blocking all three major routes of complement activation. Plasma concentrations in healthy human subjects have been reported to be 119, 219, and 5.2 ng/ml for C3a, C4a, and C5a, respectively (Table 1). It is likely that all these studies are reporting the des-arginated forms of the fragments because the assay methods cannot discriminate between the two forms. In addition, neoepitope-specific antibodies, which can discriminate between C3 and its cleavage product, detect usually the des-arginated form of C3a with higher sensitivity. Complement peptide levels are clearly elevated in inflammatory diseases and even in pregnancy (Table 1)." |