Previous studies of human in vivo complement protein levels have only compared data for neonates with that from adult sera. Here, we establish the normal concentration ranges of the following complement regulatory proteins in healthy Brazilian children of different age groups (neonates: 1 month-1 year, 1-6 years and 6-13 years) and in adults: factor H (fH), factor I (fI), C4b-binding protein (C4 BP), properdin and vitronectin. We found that the concentrations of fH, fI, properdin and vitronectin in neonates are significantly lower than in adults. Remarkably, the concentration of C4 BP is below the method resolution (<50 micro g/ml) in 76% of the sera from neonates, while adults presented 199-532 microg/ml of C4 BP in their sera. The concentration of properdin in the sera from neonates and up to 1-year-old children was less than that observed in older children. Adults presented vitronectin levels significantly higher than all the other age groups in the study. No significant sex differences in the concentrations of all the studied regulatory proteins were detected. This study reveals the ontogeny of complement system in greater detail than previously available and may point to the reasons why neonates have higher susceptibility to develop life-threatening pyogenic infections. These reference values will be of use in clinical and laboratory investigations of disorders associated with low levels of these regulatory proteins.

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Due to the increasing numbers of reported clinical cases of complement deficiency in medical centers, clinicians are now more aware of the role of the complement system in the protection against infections caused by microorganisms. Therefore, clinical laboratories are now prepared to perform a number of diagnostic tests of the complement system other than the standard 50% hemolytic component assay. Deficiencies of alternative complement pathway proteins are related to severe and recurrent infections; and the application of easy, reliable, and low-cost methods for their detection and distinction are always welcome, notably in developing countries. When activation of the alternative complement pathway is evaluated in hemolytic agarose plates, some but not all human sera cross-react to form a late linear lysis. Since the formation of this linear lysis is dependent on C3 and factor B, it is possible to use late linear lysis to routinely screen for the presence of deficiencies of alternative human complement pathway proteins such as factor B. Furthermore, since linear lysis is observed between normal human serum and primary C3-deficient serum but not between normal human serum and secondary C3-deficient serum caused by the lack of factor H or factor I, this assay may also be used to discriminate between primary and secondary C3 deficiencies.The human complement system is formed by more than 30 proteins and plays several important inflammatory and immune functions derived from its activation (10). Complement can be activated by the classical, alternative, and lectin pathways. The activation of the alternative complement pathway occurs at a slow but constant rate and is initiated by the hydrolysis of an internal thioester bond in C3 that leads to the formation of C3(H 2 O) (12). When factor B (fB) binds to C3(H 2 O), it is cleaved by factor D (fD), generating the first C3 convertase of the alternative pathway, C3(H 2 O)Bb, which cleaves C3 to C3a and C3b. C3b binding to fB, followed by cleavage by fD, generates the second C3 convertase of the alternative pathway, C3bBb. As a consequence, several molecules of C3 are cleaved to C3a and C3b in a short period of time. If this activation is not properly regulated, C3 is converted into C3b and a marked consumption of C3 is observed (secondary deficiency) (1,2,19).Factor I (fI) is one of the most important C3 regulatory proteins since it cleaves C3b to iC3b, which is subsequently cleaved by fI to produce C3c and C3d. fI requires the presence of several cofactor proteins, principally, factor H (fH), to perform its regulatory functions properly.Sera from individuals with homozygous deficiencies of fI or fH or from individuals presenting with nephritic factors have very low levels of intact C3 and low levels of fB (2,7,11,19). On the other hand, primary C3-deficient patients have little C3 or completely lack of C3 but have normal levels of fB, fH, and fI (18,19). Impairment of the complement-dependent functions is observed in patients with both primary and secondary C3 deficienc...