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

TitleElastin-Specific Autoimmunity in Smokers With Thoracic Aortic Aneurysm and Dissection is Independent of Chronic Obstructive Pulmonary Disease.
Publication TypePublication
Year2019
AuthorsGu B-H, Choi JC, Shen YH, Song L-Z, Scheurer ME, Luong A, Rodriguez A, Woodruff P, Koth L, Corry DB, Kheradmand F, LeMaire SA
JournalJ Am Heart Assoc
Volume8
Issue8
Paginatione011671
Date Published2019 Apr 16
ISSN2047-9980
KeywordsAdult, Aged, Aneurysm, Dissecting, Aortic Aneurysm, Thoracic, Autoantibodies, Autoimmunity, Case-Control Studies, CD4-Positive T-Lymphocytes, Cigarette Smoking, Cross-Sectional Studies, Elastin, Ex-Smokers, Female, Forced Expiratory Volume, Humans, Interferon-gamma, Interleukin-1beta, Leukocyte Elastase, Male, Matrix Metalloproteinase 12, Matrix Metalloproteinase 9, Middle Aged, Non-Smokers, Peptide Fragments, Pulmonary Disease, Chronic Obstructive, Smokers, Vital Capacity
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 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.

DOI10.1161/JAHA.118.011671
Alternate JournalJ Am Heart Assoc
PubMed ID30957625
PubMed Central IDPMC6507218
Grant ListR01 HL110883 / HL / NHLBI NIH HHS / United States
HHSN268200900014C / HL / NHLBI NIH HHS / United States
MS#: 
MS181
Manuscript Full Title: 
Elastin-Specific Autoimmunity in Smokers With Thoracic Aortic Aneurysm and Dissection is Independent of Chronic Obstructive Pulmonary Disease.
Manuscript Lead/Corresponding Author Affiliation: 
Clinical Center: San Francisco (University of California at San Francisco)
ECI: 
Manuscript Status: 
Published and Public