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Bronchiectasis Is a Model for Chronic Bacterial Infection Inducing Autoimmunity in Rheumatoid Arthritis

Lookup NU author(s): Professor Anthony De SoyzaORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Objective. To examine the potential of chronic severe bacterial infection to generate rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs), by studying patients with bronchiectasis (BR) alone and BR patients with rheumatoid arthritis (BR/RA).Methods. We studied 122 patients with BR alone, 50 patients with BR/RA, and 50 RA patients without lung disease, as well as 87 patients with asthma and 79 healthy subjects as controls. RF levels were measured using an automated analyzer, and cyclic citrullinated peptide 2 (CCP-2) was used to detect ACPAs. The fine specificities of citrullinated -enolase peptide 1 (CEP-1), Cit-vimentin, and Cit-fibrinogen to their arginine-containing control peptides (arginine-containing alpha-enolase peptide 1 [REP-1], vimentin, and fibrinogen) were measured by enzyme-linked immunosorbent assay.Results. Among the BR patients and control subjects, 39% and 42%, respectively, were ever-smokers. The frequency of RF positivity in serum was increased in BR patients compared with controls (25% versus 10%), as were the frequencies of antibodies to CCP-2 (5% versus 0%), CEP-1 (7% versus 4%), Cit-vimentin (7% versus 4%), and Cit-fibrinogen (12% versus 4%), although only the differences for RF and Cit-fibrinogen were significant (P < 0.05). We observed a corresponding increase in the frequency of antibodies to the arginine-containing control peptides in BR patients compared with controls (for REP-1, 19% versus 4% [P < 0.01]; for vimentin, 16% versus 4% [P < 0.05]), demonstrating that the ACPA response in patients with BR is not citrulline specific. The lack of citrulline specificity was further confirmed by absorption studies. In BR/RA patients, all ACPA responses were highly citrulline specific.Conclusion. Bronchiectasis is an unusual but potent model for the induction of autoimmunity in RA by bacterial infection in the lung. Our study suggests that the ACPA response is not citrulline specific during the early stages of tolerance breakdown but becomes more specific in patients with BR in whom BR/RA develops.

Publication metadata

Author(s): Quirke AM, Perry E, Cartwright A, Kelly C, De Soyza A, Eggleton P, Hutchinson D, Venables PJ

Publication type: Article

Publication status: Published

Journal: Arthritis & Rheumatology

Year: 2015

Volume: 67

Issue: 9

Pages: 2335-2342

Print publication date: 01/09/2015

Online publication date: 26/08/2015

Acceptance date: 26/05/2015

Date deposited: 09/10/2015

ISSN (print): 2326-5191

ISSN (electronic): 2326-5205

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/art.39226


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Funder referenceFunder name
115142-2European Union
19894Arthritis Research UK
HEALTH-F2-2010261460European Union