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J Am Heart Assoc. 2019 Apr 16;8(8):e011671. doi: 10.1161/JAHA.118.011671.

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

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1 Department of Medicine, Pulmonary and Critical Care Baylor College of Medicine Houston TX.
2 Division of Cardiothoracic Surgery Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston TX.
3 Cardiovascular Research Institute Baylor College of Medicine Houston TX.
7 Department of Cardiovascular Surgery Texas Heart Institute Houston TX.
4 Section of Hematology-Oncology Department of Pediatrics Baylor College of Medicine Houston TX.
8 Department of Otorhinolaryngology - Head and Neck Surgery McGovern Medical School University of Texas Health Science Center Houston TX.
5 Departments of Pathology and Immunology Baylor College of Medicine Houston TX.
6 Biology of Inflammation Center Baylor College of Medicine Houston TX.
9 University of California San Francisco San Francisco CA.
10 Center for Translational Research in Inflammatory Diseases Michael E. DeBakey VA Houston TX.
11 CHI St Luke's Health-Baylor St Luke's Medical Center Houston TX.


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.


aneurysm; immune system; immunology; inflammation

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