{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:11:00Z","timestamp":1790856660639,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,12,30]],"date-time":"2013-12-30T00:00:00Z","timestamp":1388361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>It has been suggested that immunologic events in the lungs may be involved in triggering immunity, in particular production of anti\u2013citrullinated protein antibodies (ACPAs) during early phases of rheumatoid arthritis (RA). The aim of this study was to investigate the structural and immunologic features of the lungs in incident cases of early RA in relation to ACPA presence and smoking status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>High\u2010resolution computed tomography (HRCT) was used to examine the lungs of 105 patients with early, untreated RA (70 with ACPA\u2010positive RA and 35 with ACPA\u2010negative RA) and 43 healthy individuals. Bronchoscopy with collection of bronchoalveolar lavage (BAL) fluid and mucosal bronchial biopsy specimens was performed in 23 RA patients. The presence of citrullinated proteins in the bronchial tissue was detected by immunohistochemical staining. ACPAs (detected with an anti\u2013cyclic citrullinated peptide 2 test) and total Ig levels were determined in the sera and BAL fluid of RA patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HRCT imaging revealed that 63% of ACPA\u2010positive RA patients had parenchymal lung abnormalities, compared with only 37% of ACPA\u2010negative RA patients and 30% of healthy controls (each <jats:italic>P<\/jats:italic> &lt; 0.05). These significant differences remained after adjustment for smoking status. Airway changes detected by HRCT were more frequent in RA patients than in healthy controls (66% versus 42%; <jats:italic>P<\/jats:italic> &lt; 0.05), but there was no difference between ACPA\u2010positive and ACPA\u2010negative RA patients. Immunohistochemical studies of the bronchial tissue showed increased staining for citrullinated proteins in ACPA\u2010positive RA patients compared with ACPA\u2010negative RA patients (<jats:italic>P<\/jats:italic> &lt; 0.05). ACPA levels were relatively higher in the BAL fluid as compared with the sera of ACPA\u2010positive RA patients, suggesting that there is local production of ACPAs in the lungs of these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The presence of ACPAs is associated with parenchymal lung abnormalities, site\u2010specific citrullination, and antibody enrichment in the lungs early in the development of ACPA\u2010positive RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38201","type":"journal-article","created":{"date-parts":[[2013,10,21]],"date-time":"2013-10-21T15:45:39Z","timestamp":1382370339000},"page":"31-39","source":"Crossref","is-referenced-by-count":225,"title":["Structural Changes and Antibody Enrichment in the Lungs Are Early Features of Anti\u2013Citrullinated Protein Antibody\u2013Positive Rheumatoid Arthritis"],"prefix":"10.1002","volume":"66","author":[{"given":"Gudrun","family":"Reynisdottir","sequence":"first","affiliation":[{"name":"Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Karimi","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Joshua","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga","family":"Olsen","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aase Haj","family":"Hensvold","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Harju","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Engstr\u00f6m","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Grunewald","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Nyren","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Eklund","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Klareskog","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl Magnus","family":"Sk\u00f6ld","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Irinel Catrina","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,12,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11223"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20018"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0249"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34344"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380107"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.09.024"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/4-431-27512-6"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1183\/09041950.005s1693","article-title":"Lung volumes and forced ventilatory flows: report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. 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