Immunological crossreactivity between Lp(a) and the third component of complement

Lipoprotein(a) [Lp(a)] is known to be an independent risk factor for atherosclerosis, yet little is known about its physiological role. During the authors investigation of the site of synthesis of Lp(a), they made the observation that the third component of complement (C3) reacts with antisera to Lp(a). Hep G-2 cells or rhesus liver organ cultures were labelled using 35S-methionine in serum-free, methionine-free DMEM. The labelled media were immunoprecipitated with antisera raised in the goat and the rabbit against Lp(a) and apolipoprotein(a) [apo(a)]. The immunoprecipitates were subjected to electrophoresis on 2.5 - 16% gradient gels and visualized by autoradiography. All antisera consistently precipitated a significant amount of C3. This reaction with C3 could be inhibited by competition with pure preparations of Lp(a) and apo(a) or by preincubation of the medium with antiserum to C3. In addition, immunoprecipitation of C3 by anti-C3 was inhibited by competition with both apo(a) and Lp(a). No cross-reactivity was observed with antisera to apoB, apoE, normal rabbit serum, or purified non-specific rabbit IgG. This unexpected crossreactivity between Lp(a) and C3, observed in vitro, may have biological relevance and suggests a possible relationship between Lp(a) and the immune system