PURPOSE: Previous work has revealed that nonspecific abdominal aortic aneurysms (AAAs) have a prominent infiltration of inflammatory cells and that soluble extracts of AAA tissue are rich in immunoglobulins. These observations raise the question whether autoimmune mechanisms play a role in the pathogenesis or progression of AAA disease. The hypothesis of this investigation was that IgG purified from aneurysmal specimens would be immunoreactive with normal components of the aortic wall (by means of immunohistochemistry) and with soluble proteins extracted from normal aortic tissue (by Western immunoblotting methods). METHODS: Immunoglobulin G extracted from AAA homogenates was used to detect immunohistochemical reactivity to connective tissue components in fixed sections of normal aorta obtained from an organ donor. Immunoblotting techniques were used to compare the reactivity of IgG (detected with secondary goat antihuman antibody) from 14 patients with AAA with soluble proteins extracted from normal and aneurysmal aortas. Immunoglobulins G purified from extracts obtained from nine patients with no AAA were used for control experiments. RESULTS: A unique band at approximately 80 kd was visualized when the filters were probed with IgG from 11 (79%) of 14 patients with AAA compared with only one (11%) of nine control subjects (P = .002 by Fisher's exact test). Immunoglobulins G from patients with AAA codistributed with matrix fibers in normal aortic sections, particularly in the adventitia (suggestive of a microfibrillar component). CONCLUSION: Our findings suggest that there are autoimmune features of AAA disease that might not only be informative in terms of AAA origin but also lead to more precise forms of pharmacologic down-regulation of disease progression.
PURPOSE: Previous work has revealed that nonspecific abdominal aortic aneurysms (AAAs) have a prominent infiltration of inflammatory cells and that soluble extracts of AAA tissue are rich in immunoglobulins. These observations raise the question whether autoimmune mechanisms play a role in the pathogenesis or progression of AAA disease. The hypothesis of this investigation was that IgG purified from aneurysmal specimens would be immunoreactive with normal components of the aortic wall (by means of immunohistochemistry) and with soluble proteins extracted from normal aortic tissue (by Western immunoblotting methods). METHODS: Immunoglobulin G extracted from AAA homogenates was used to detect immunohistochemical reactivity to connective tissue components in fixed sections of normal aorta obtained from an organ donor. Immunoblotting techniques were used to compare the reactivity of IgG (detected with secondary goat antihuman antibody) from 14 patients with AAA with soluble proteins extracted from normal and aneurysmal aortas. Immunoglobulins G purified from extracts obtained from nine patients with no AAA were used for control experiments. RESULTS: A unique band at approximately 80 kd was visualized when the filters were probed with IgG from 11 (79%) of 14 patients with AAA compared with only one (11%) of nine control subjects (P = .002 by Fisher's exact test). Immunoglobulins G from patients with AAA codistributed with matrix fibers in normal aortic sections, particularly in the adventitia (suggestive of a microfibrillar component). CONCLUSION: Our findings suggest that there are autoimmune features of AAA disease that might not only be informative in terms of AAA origin but also lead to more precise forms of pharmacologic down-regulation of disease progression.
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