Studies on the nature of heat-labile anti-complementary activity in normal human serum

Heat-labile anti-complementary activity (ACA) appears in normal human serum during storage or heating as endogenous haemolytic activity disappears. Following gel filtration of unheated serum, two peaks of heat-labile ACA are present. The ACA of both whole and fractionated serum has previously been attributed to the presence of heat-labile immunoglobulin aggregates or immune complexes. Our data demonstrate that the heavy peak of ACA obtained by gel filtration does not bind to ¹²⁵I-Clq or to Raji cells, and that its effect is abolished by Cl̇INH, suggesting that it represents Cl̇ rather than immunoglobulin aggregates or immune complexes. The lighter peak of ACA in fractionated serum has the functional characteristics of Cl̇s and free Cl̇s is demonstrable in fractions containing this activity. The ACA of whole serum likewise has functional characteristics of Cl̇ The anti-complementary effect of Cl̇ on guinea pig complement would not be evident in the complement fixation assay until most endogenous haemolytic activity in human serum has been inactivated, either by heat or by storage. Cl̇INH only partially inhibits this ACA in serum or in solutions containing isolated Cl̇ in high concentrations. These observations indicate that heat-labile ACA in whole or fractionated sera is due to the presence of Cl̇ and Cl̇s and that this activity cannot be taken as evidence for the presence of immune complexes.