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.

Keywords

• aneurysm
• immune system
• immunology
• inflammation