COMPLEMENT ACTIVATION AND SUBCLASSIFICATION OF TISSUE IMMUNOGLOBULIN-G IN THE ABDOMINAL AORTIC-ANEURYSM

Features of autoimmunity in abdominal aortic aneurysm (AAA) have been described, including increases in IgG content, The present experiments were carried out to determine (1) whether the increases in IgG are su bclass specific and (2) whether the IgG complex is associated with an increase in the isoforms of complement C3. Seven AAA, four athero-occl usive (AOD), and two normal (NL) aortic tissue extracts were evaluated for immunoreactive complement (C3) components, both by ELISA and by W estern immunoblots (probed with a polyclonal goat anti-human C3). The extracts were also assayed for each of the four subclasses of IgG by E LISA (monoclonal mouse anti-human IgGs). Compared to the amounts of Ig G by subclass in normal aorta, AAAs had increases of 193-fold in IgG1, 160-fold in IgG2, 389-fold in IgG3, and 627-fold in IgG4, Increases r elative to AOD by subclass were smaller, but each subclass was statist ically significantly elevated (P < 0.01) over NL or over AOD. There wa s a 125-fold increase in immunoreactive C3 by ELISA in AAA vs NL, and Western immunoblotting techniques revealed the presence of multiple C3 degradation products. Increases in IgG1, 2, and 3 may be responsible for activation of complement in AAA by the classical pathway. Since th e complement system is one of the major effector pathways of inflammat ion, the presence of complement-fixing IgG subclasses along with incre ased C3 in the aneurysm wall may be an important mechanism promoting m atrix proteolysis in AAA. (C) 1996 Academic Press, Inc.