Activation of Complement

Activation of the complement system by IgA has been a controversial subject since Ishizaka et al. (1) and South et al. (2) observed that C1 was not fixed by IgA. Lack of complement activation has also been inferred from reports that secretory IgA antibodies were unable to opsonize or promote bacterial killing in the presence of complement (3 6). On the other hand, there is evidence that some complementdependent functions occur in the presence of lgA antibodies. Adinolfi et al. (7) showed that Escherichia coli could be lysed by complement in the presence of secretory IgA and lysozyme. Knop et al. (8) and Henson et al. (9) demonstrated stimulation of phagocytosis by neutrophils in the presence of IgA and complement. After "interfacial" aggregation, secretory IgA was able to consume C3-9 without fixing CI; removal of the secretory component together with the Fc portion of the molecule did not alter the mode or extent of complement consumption (10). Also, chemically aggregated IgA myeloma proteins and their fragments have been reported to activate complement by both the classical and alternative pathways (11-15). However, only one previous study has demonstrated activation of complement by IgA myeloma proteins acting as antibodies (16). In this study solubilization of immune complexes prepared with unfractionated mouse ascites fluid induced by antigen-binding myelomas was used as an indirect measure of activation of the alternative pathway in mouse and guinea pig serum. Activation of the alternative complement pathway by IgA has also been suggested in some clinical situations. Soter et al. (17) reported a patient with IgA cryoglobulinemia who showed low levels of C3 and factor B (also known as C3 activator) concurrent with their increased catabolism. By immunofluorescence, IgA, C3, and factor B have been detected at the dermal-epidermal junction in patients with dermatitis herpetiformis (18) and in the glomeruli in Berger's disease (19). Early complement components were not observed in either case. Although some of the results in the above experimental studies could have been due to contamination of IgA with other classes of immunoglobulins, the presence of complement components in secretions (20-23) where IgA is the primary immunoglobulin (24) could be taken to suggest the possibility of interaction. The present work