{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:12:19Z","timestamp":1790874739727,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T00:00:00Z","timestamp":1574726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["K2014\u201052X\u201014045\u201014\u20103"],"award-info":[{"award-number":["K2014\u201052X\u201014045\u201014\u20103"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004348","name":"Stockholms L\u00e4ns Landsting","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004348","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2020,1]]},"abstract":"Objective<\/jats:title>Autoantibodies targeting histidyl\u2013transfer RNA<\/jats:styled-content> synthetase (HisRS<\/jats:styled-content>; anti\u2013Jo\u20101) are common in the idiopathic inflammatory myopathies (IIM<\/jats:styled-content>s) and antisynthetase syndrome. This study was undertaken to investigate immunity against HisRS<\/jats:styled-content> in the blood and lungs of patients with IIM<\/jats:styled-content>\/antisynthetase syndrome.<\/jats:p><\/jats:sec>Methods<\/jats:title>Bronchoalveolar lavage (BAL<\/jats:styled-content>) fluid, BAL<\/jats:styled-content> fluid cells, and peripheral blood mononuclear cells (PBMC<\/jats:styled-content>s) from patients with IIM<\/jats:styled-content>\/antisynthetase syndrome (n = 24) were stimulated with full\u2010length HisRS<\/jats:styled-content> protein or a HisRS<\/jats:styled-content>\u2010derived peptide (HisRS<\/jats:styled-content>11\u201323<\/jats:sub>). BAL<\/jats:styled-content> fluid and PBMC<\/jats:styled-content>s from patients with sarcoidosis (n = 7) and healthy subjects (n = 12) were included as controls. The CD<\/jats:styled-content>4+ T cell response was determined according to levels of CD<\/jats:styled-content>40L up\u2010regulation and cytokine expression using flow cytometry. Anti\u2013Jo\u20101 autoantibody responses in the serum and BAL<\/jats:styled-content> fluid were assessed by enzyme\u2010linked immunosorbent assay. Lung biopsy samples from patients with IIM<\/jats:styled-content>\/antisynthetase syndrome (n = 14) were investigated by immunohistochemistry.<\/jats:p><\/jats:sec>Results<\/jats:title>In BAL<\/jats:styled-content> fluid, CD<\/jats:styled-content>4+ T cells from 3 of 4 patients with IIM<\/jats:styled-content>\/antisynthetase syndrome responded to stimulation with HisRS<\/jats:styled-content> protein, as measured by the median fold change in CD<\/jats:styled-content>40L expresssion in stimulated cells compared to unstimulated cells (median fold change 3.6, interquartile range [IQR<\/jats:styled-content>] 2.7\u201314.7), and 2 of 3 patients with IIM<\/jats:styled-content>\/antisynthetase syndrome had the highest responses to HisRS<\/jats:styled-content>11\u201323<\/jats:sub> (median fold change 88, IQR<\/jats:styled-content> 27\u2013149).<\/jats:sub> In PBMC<\/jats:styled-content>s, CD<\/jats:styled-content>4+ T cells from 14 of 18 patients with IIM<\/jats:styled-content>\/antisynthetase syndrome responded to HisRS<\/jats:styled-content> protein (median fold change 7.38, IQR<\/jats:styled-content> 2.69\u201331.86; P<\/jats:italic> < 0.001), whereas a HisRS<\/jats:styled-content>11\u201323<\/jats:sub> response was present in 11 of 14 patients with IIM<\/jats:styled-content>\/antisynthetase syndrome (median fold change 3.4, IQR<\/jats:styled-content> 1.87\u201310.9; P<\/jats:italic> < 0.001). In the control group, there was a HisRS<\/jats:styled-content>11\u201323<\/jats:sub> response in 3 of 7 patients with sarcoidosis (median fold change 2.09, IQR<\/jats:styled-content> 1.45\u20133.29) and in 5 of 12 healthy controls (median fold change 2, IQR<\/jats:styled-content> 1.89\u20132.42). CD<\/jats:styled-content>4+ T cells from patients with IIM<\/jats:styled-content>\/antisynthetase syndrome displayed a pronounced Th1 phenotype in the BAL<\/jats:styled-content> fluid when compared to the PBMC<\/jats:styled-content>s (P<\/jats:italic> < 0.001), producing high amounts of interferon\u2010\u03b3 and interleukin\u20102 following stimulation. Anti\u2013Jo\u20101 autoantibodies were detected in BAL<\/jats:styled-content> fluid and germinal center (GC<\/jats:styled-content>)\u2013like structures were seen in the lung biopsy samples from patients with IIM<\/jats:styled-content>\/antisynthetase syndrome.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>The results of this study demonstrate a pronounced presence of HisRS<\/jats:styled-content>\u2010reactive CD<\/jats:styled-content>4+ T cells in PBMC<\/jats:styled-content>s and BAL<\/jats:styled-content> fluid cells from patients with IIM<\/jats:styled-content>\/antisynthetase syndrome as compared to patients with sarcoidosis and healthy controls. These findings, combined with the presence of anti\u2013Jo\u20101 autoantibodies in BAL<\/jats:styled-content> fluid and GC<\/jats:styled-content>\u2010like structures in the lungs, suggest that immune activation against HisRS<\/jats:styled-content> might take place within the lungs of patients with IIM<\/jats:styled-content>\/antisynthetase syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41075","type":"journal-article","created":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T07:03:41Z","timestamp":1565593421000},"page":"179-191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Proinflammatory Histidyl\u2013Transfer RNA<\/scp> Synthetase\u2013Specific CD<\/scp>4+ T Cells in the Blood and Lungs of Patients With Idiopathic Inflammatory Myopathies"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7095-211X","authenticated-orcid":false,"given":"Angeles 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