Journal
JOURNAL OF THE AMERICAN HEART ASSOCIATION
Volume 8, Issue 8, Pages -Publisher
WILEY
DOI: 10.1161/JAHA.118.011671
Keywords
aneurysm; immune system; immunology; inflammation
Categories
Funding
- VA Merit [CX000104]
- Baylor College of Medicine from Cardiovascular Research Institute
- NHLBI [HHSN268200900014C]
- Jimmy and Roberta Howell Professorship in Cardiovascular Surgery
- [R01 HL110883]
- [HL140398]
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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-7, 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.
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