COPD is associated with production of autoantibodies to a broad spectrum of self-antigens, correlative with disease phenotype
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The role of autoimmune pathology in development and progression of chronic obstructive pulmonary disease (COPD) is becoming increasingly appreciated. In this study, we identified serum autoantibody reactivities associated with chronic bronchitis or emphysema, as well as systemic autoimmunity and associated lung disease. Using autoantigen array analysis, we demonstrated that COPD patients produce autoantibodies reactive to a broad spectrum of self-antigens. Further, the level and reactivities of these antibodies, or autoantibody profile, correlated with disease phenotype. Patients with emphysema produced autoantibodies of higher titer and reactive to an increased number of array antigens. Strikingly, the autoantibody reactivities observed in emphysema were increased over those detected in rheumatoid arthritis patients, and included similar reactivities to those associated with lupus. These findings raise the possibility that autoantibody profiles may be used to determine COPD risk, as well as provide a diagnostic and prognostic tool. They shed light on the heterogeneity of autoantibody reactivities associated with COPD phenotype and could be of use in the personalization of medical treatment, including determining and monitoring therapeutic interventions.
KeywordsCOPD SLE RA ILD Autoantibodies Antigen array
The authors would like to thank Dr. Steve Groshong for his contribution to histological analyses, and the patients of National Jewish Health for their blood donations. This work was funded by the NJC COPD Institutional Program and the generous donation by Joel Farkas to National Jewish Health.
- 1.Kochanek KD, Xu J, Murphy SL, Miniño AM, Kung H-C. Deaths: preliminary data for 2009. National Vital Statistics Reports: US Department of Health and Human Services. Centers for Disease Control and Prevention. National Center for Health Statistics. 2011:51. http://www.cdc.gov/nchs/data/nvsr/nvsr59/nvsr59_04.pdf. Accessed 14 Jun 2012.
- 2.The top 10 causes of death. WHO Media Centre: Fact Sheet N˚310. World Health Organization. 2011. http://www.who.int/mediacentre/factsheets/fs310/en/. Accessed 14 Jun 2012.
- 5.Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS, Committee GS. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med. 2001;163:1256–76.PubMedGoogle Scholar
- 6.Gamble E, Grootendorst DC, Hattotuwa K, O’Shaughnessy T, Ram FS, Qiu Y, Zhu J, Vignola AM, Kroegel C, Morell F, Pavord ID, Rabe KF, Jeffery PK, Barnes NC. Airway mucosal inflammation in COPD is similar in smokers and ex-smokers: a pooled analysis. Eur Respir J. 2007;30:467–71.PubMedCrossRefGoogle Scholar
- 9.Hagstad S, Ekerljung L, Lindberg A, Backman H, Rönmark E, Lundbäck B. COPD among non-smokers—Report from the Obstructive Lung Disease in Northern Sweden (OLIN) studies. Respir Med. 2012;106(7):980–8.Google Scholar
- 12.Kirkham PA, Caramori G, Casolari P, Papi AA, Edwards M, Shamji B, Triantaphyllopoulos K, Hussain F, Pinart M, Khan Y, Heinemann L, Stevens L, Yeadon M, Barnes PJ, Chung KF, Adcock IM. Oxidative stress-induced antibodies to carbonyl-modified protein correlate with severity of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011;184:796–802.PubMedCrossRefGoogle Scholar
- 23.Alimohammadi M, Dubois N, Sköldberg F, Hallgren A, Tardivel I, Hedstrand H, Haavik J, Husebye ES, Gustafsson J, Rorsman F, Meloni A, Janson C, Vialettes B, Kajosaari M, Egner W, Sargur R, Pontén F, Amoura Z, Grimfeld A, De Luca F, Betterle C, Perheentupa J, Kämpe O, Carel JC. Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen. Proc Natl Acad Sci USA. 2009;106:4396–401.PubMedCrossRefGoogle Scholar
- 24.Shum AK, DeVoss J, Tan CL, Hou Y, Johannes K, O’Gorman CS, Jones KD, Sochett EB, Fong L, Anderson MS. Identification of an autoantigen demonstrates a link between interstitial lung disease and a defect in central tolerance. Sci Transl Med. 2009; 1:9ra20.Google Scholar
- 29.Toyoshima M, Chida K, Suda T, Sato M. Is autoimmunity really related to the pathogenesis of COPD? Am J Respir Crit Care Med. 2011; 184:1212–3; author reply 3.Google Scholar
- 35.Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease.: Global Initiative for Chronic Obstructive Lung Disease, Inc. 2011:80.Google Scholar
- 36.Society AT, Society ER. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med. 2002; 165:277–304.Google Scholar
- 45.Popler J, Alimohammadi M, Kämpe O, Dalin F, Dishop MK, Barker JM, Moriarty-Kelsey M, Soep JB, Deterding RR. Autoimmune polyendocrine syndrome type 1: utility of KCNRG autoantibodies as a marker of active pulmonary disease and successful treatment with rituximab. Pediatr Pulmonol. 2012;47:84–7.PubMedCrossRefGoogle Scholar