Elastin-Specific Autoimmunity in Smokers With Thoracic Aortic Aneurysm and Dissection is Independent of Chronic Obstructive Pulmonary Disease

Abstract

Background: Thoracic aortic aneurysm (TAA) and dissection (TAD) are characterized by progressive disorganization of the aortic wall matrix, including elastin, a highly immunogenic molecule. Whether acquired autoimmune responses can be detected in TAA/TAD patients who are smokers is unknown. The objectives of this study were to determine whether TAA/TAD smokers have increased T-cell responses to human elastin fragments, and to determine whether autoimmune responses in TAA/TAD smokers are dependent on chronic obstructive pulmonary disease. Methods and Results: In a cross-sectional study (N=86), we examined peripheral blood CD4+ T cell responses to elastin fragments in never-, former-, or current-smokers with or without TAA/TAD. CD4+ T cells were co-cultured with irradiated autologous peripheral blood CD1a+/CD14+ antigen presenting cells pulsed with or without elastin fragments to measure cytokine production. Baseline plasma concentration of anti-elastin antibodies and elastin-degrading enzymes (eg, matrix metalloproteinase-9, and -12, and neutrophil elastase) were measured in the same cohort. elastin fragment-specific CD4+ T cell expression of interferon-γ, and anti-elastin antibodies were dependent on history of smoking in TAA/TAD patients but were independent of chronic obstructive pulmonary disease. Matrix metalloproteinase-9, and -12, and neutrophil elastase plasma concentrations were also significantly elevated in ever-smokers with TAA/TAD. Conclusions: Cigarette smoke is associated with loss of self-tolerance and induction of elastin-specific autoreactive T- and B-cell responses in patients with TAA/TAD. Development of peripheral blood biomarkers to track immunity to self-antigens could be used to identify and potentially prognosticate susceptibility to TAA/TAD in smokers.