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

J Am Heart Assoc. 2019 Apr 16;8(8):e011671. 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.

Keywords: aneurysm; immune system; immunology; inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aortic Aneurysm, Thoracic / epidemiology
  • Aortic Aneurysm, Thoracic / immunology*
  • Aortic Aneurysm, Thoracic / metabolism
  • Aortic Dissection / epidemiology
  • Aortic Dissection / immunology*
  • Aortic Dissection / metabolism
  • Autoantibodies / immunology*
  • Autoimmunity*
  • CD4-Positive T-Lymphocytes / immunology*
  • Case-Control Studies
  • Cigarette Smoking / immunology*
  • Cigarette Smoking / metabolism
  • Cross-Sectional Studies
  • Elastin / immunology*
  • Elastin / metabolism
  • Ex-Smokers
  • Female
  • Forced Expiratory Volume
  • Humans
  • Interferon-gamma / immunology
  • Interleukin-1beta / immunology
  • Leukocyte Elastase / metabolism
  • Male
  • Matrix Metalloproteinase 12 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Non-Smokers
  • Peptide Fragments / immunology
  • Pulmonary Disease, Chronic Obstructive / epidemiology
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Smokers
  • Vital Capacity


  • Autoantibodies
  • IFNG protein, human
  • IL1B protein, human
  • Interleukin-1beta
  • Peptide Fragments
  • Interferon-gamma
  • Elastin
  • ELANE protein, human
  • Leukocyte Elastase
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • MMP12 protein, human
  • Matrix Metalloproteinase 12