{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:17:34Z","timestamp":1785251854384,"version":"3.55.0"},"reference-count":25,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2015,8,26]],"date-time":"2015-08-26T00:00:00Z","timestamp":1440547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"crossref","award":["19894"],"award-info":[{"award-number":["19894"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"name":"IMI project BTCure","award":["115142-2"],"award-info":[{"award-number":["115142-2"]}]},{"name":"7th Framework Programme project Gums and Joints","award":["HEALTH-F2-2010-261460"],"award-info":[{"award-number":["HEALTH-F2-2010-261460"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine the potential of chronic severe bacterial infection to generate rheumatoid factor (RF) and anti\u2013citrullinated protein antibodies (ACPAs), by studying patients with bronchiectasis (BR) alone and BR patients with rheumatoid arthritis (BR\/RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u20102) was used to detect ACPAs. The fine specificities of citrullinated \u03b1\u2010enolase peptide 1 (CEP\u20101), Cit\u2010vimentin, and Cit\u2010fibrinogen to their arginine\u2010containing control peptides (arginine\u2010containing \u03b1\u2010enolase peptide 1 [REP\u20101], vimentin, and fibrinogen) were measured by enzyme\u2010linked immunosorbent assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the BR patients and control subjects, 39% and 42%, respectively, were ever\u2010smokers. 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\u20102 (5% versus 0%), CEP\u20101 (7% versus 4%), Cit\u2010vimentin (7% versus 4%), and Cit\u2010fibrinogen (12% versus 4%), although only the differences for RF and Cit\u2010fibrinogen were significant (<jats:italic>P<\/jats:italic> &lt; 0.05). We observed a corresponding increase in the frequency of antibodies to the arginine\u2010containing control peptides in BR patients compared with controls (for REP\u20101, 19% versus 4% [<jats:italic>P<\/jats:italic> &lt; 0.01]; for vimentin, 16% versus 4% [<jats:italic>P<\/jats:italic> &lt; 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39226","type":"journal-article","created":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T14:00:50Z","timestamp":1432735250000},"page":"2335-2342","source":"Crossref","is-referenced-by-count":76,"title":["Bronchiectasis Is a Model for Chronic Bacterial Infection Inducing Autoimmunity in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"67","author":[{"given":"Anne\u2010Marie","family":"Quirke","sequence":"first","affiliation":[{"name":"Kennedy Institute, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Perry","sequence":"additional","affiliation":[{"name":"Queen Elizabeth Hospital, Gateshead, UK, and University of Exeter Medical School Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Cartwright","sequence":"additional","affiliation":[{"name":"Kennedy Institute, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive","family":"Kelly","sequence":"additional","affiliation":[{"name":"Queen Elizabeth Hospital Gateshead UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"De Soyza","sequence":"additional","affiliation":[{"name":"Newcastle University and The Freeman Hospital Newcastle UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Eggleton","sequence":"additional","affiliation":[{"name":"University of Exeter Medical School Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Royal Cornwall Hospital Truro UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Venables","sequence":"additional","affiliation":[{"name":"Kennedy Institute, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,8,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2009.00850.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11223"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21575"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-004-6641-z"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2011.01.014"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0520-x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.38"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.28"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12138"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202701"},{"key":"e_1_2_7_12_1","first-page":"239","article-title":"Pulmonary infections and rheumatoid arthritis","volume":"36","author":"Walker WC.","year":"1967","journal-title":"Q J Med"},{"key":"e_1_2_7_13_1","first-page":"531","article-title":"Prevalence of symptomatic bronchiectasis in patients with rheumatoid arthritis","volume":"64","author":"Allain J","year":"1997","journal-title":"Rev Rhum Engl Ed"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00064014"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0007-0971(78)90043-8"},{"key":"e_1_2_7_16_1","first-page":"451","article-title":"The influence of infection on titres of antiglobulin antibodies","volume":"8","author":"Waller M","year":"1971","journal-title":"Clin Exp Immunol"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27584"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23936"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/726598"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e32801127c8"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205498"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33489"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.131341"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keu165"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34344"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2012.03.006"}],"container-title":["Arthritis &amp; 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