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

• Published in: Journal of the American Heart Association 2019-04, Vol.8 (8), p.e011671-e011671
• Main Authors: Gu, Bon-Hee, Choi, Justin C, Shen, Ying H, Song, Li-Zhen, Scheurer, Michael E, Luong, Amber, Rodriguez, Antony, Woodruff, Prescott, Koth, Laura, Corry, David B, Kheradmand, Farrah, LeMaire, Scott A
• Format: Article
• Language: English
• Subjects: Adult; Aged; aneurysm; Aneurysm, Dissecting - epidemiology; Aneurysm, Dissecting - immunology; Aneurysm, Dissecting - metabolism; Aortic Aneurysm, Thoracic - epidemiology; Aortic Aneurysm, Thoracic - immunology; Aortic Aneurysm, Thoracic - metabolism; Autoantibodies - immunology; Autoimmunity; Case-Control Studies; CD4-Positive T-Lymphocytes - immunology; Cigarette Smoking - immunology; Cigarette Smoking - metabolism; Cross-Sectional Studies; Elastin - immunology; Elastin - metabolism; Ex-Smokers; Female; Forced Expiratory Volume; Humans; immune system; immunology; inflammation; Interferon-gamma - immunology; Interleukin-1beta - immunology; Leukocyte Elastase - metabolism; Male; Matrix Metalloproteinase 12 - metabolism; Matrix Metalloproteinase 9 - metabolism; Middle Aged; Non-Smokers; Original Research; Peptide Fragments - immunology; Pulmonary Disease, Chronic Obstructive - epidemiology; Pulmonary Disease, Chronic Obstructive - immunology; Smokers; Vital Capacity
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.118.011671

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 CD 4 T cell responses to elastin fragments in never-, former-, or current-smokers with or without TAA / TAD . CD 4 T cells were co-cultured with irradiated autologous peripheral blood CD 1a / CD 14 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 CD 4 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.