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 subclass specific and (2) whether the IgG complex is associated with an increase in the isoforms of complement C3. Seven AAA, four athero-occlusive (AOD), and two normal (NL) aortic tissue extracts were evaluated for immunoreactive complement (C3) components, both by ELISA and by Western immunoblots (probed with a polyclonal goat anti-human C3). The extracts were also assayed for each of the four subclasses of IgG by ELISA (monoclonal mouse anti-human IgGs). Compared to the amounts of IgG 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 relative to AOD by subclass were smaller, but each subclass was statistically significantly elevated (P < 0.01) over NL or over AOD. There was 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 the complement system is one of the major effector pathways of inflammation, the presence of complement-fixing IgG subclasses along with increased C3 in the aneurysm wall may be an important mechanism promoting matrix proteolysis in AAA.