Abstract
Chronic obstructive pulmonary disease and emphysema are common destructive inflammatory diseases that are leading causes of death worldwide. Here we show that emphysema is an autoimmune disease characterized by the presence of antielastin antibody and T-helper type 1 (TH1) responses, which correlate with emphysema severity. These findings link emphysema to adaptive immunity against a specific lung antigen and suggest the potential for autoimmune pathology of other elastin-rich tissues such as the arteries and skin of smokers.
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Acknowledgements
We thank D. Spencer and B. Zheng for their comments, and R. Wang (Baylor College of Medicine) for providing antibodies to HLA. We thank P. Smithwick, S. Perusich, R. Williams and N. Hanania for their assistance in recruiting subjects. Supported by grants to F.K. and D.B.C. from the US National Institutes of Health and the Alpha 1 Foundation.
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Contributions
S.H.-L, S.G., A.G. and L.S. conducted the experiments. V.B., S.G.-W., L.G. and J.H.-B. contributed to the analysis of subject characteristics and tissue samples. J.H. and F.B. provided surgical lung samples. H.O.C., S.C. and C.S.-B. performed emphysema scoring. D.B.C. and F.K. conceived the project, designed experiments and wrote the manuscript.
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Supplementary information
Supplementary Fig. 1
T cell responses to elastin peptides and correlation with lung disease (PDF 541 kb)
Supplementary Fig. 2
Cumulative ELISpot data for lung anti-elastin antibody-secreting cells in Control (n=6) and Emphysema (n=6) groups. (PDF 267 kb)
Supplementary Fig. 3
TR cell function in vitro. (PDF 429 kb)
Supplementary Fig. 4
Reduced FoxP3 expression and IL-10 in emphysema. (PDF 139 kb)
Supplementary Table 1
Clinical characteristics of subjects used for Peripheral Blood Mononuclear Cell (PBMC) and Lung Tissue studies (PDF 66 kb)
Supplementary Table 2
MHC class II blocking antibody attenuate T cell responses to elastin (PDF 58 kb)
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Lee, SH., Goswami, S., Grudo, A. et al. Antielastin autoimmunity in tobacco smoking–induced emphysema. Nat Med 13, 567–569 (2007). https://doi.org/10.1038/nm1583
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DOI: https://doi.org/10.1038/nm1583
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