{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:18:08Z","timestamp":1785251888997,"version":"3.55.0"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01HL112707"],"award-info":[{"award-number":["U01HL112707"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01HL112695"],"award-info":[{"award-number":["U01HL112695"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001515","name":"Britton Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001515","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Sarcoidosis, a multi-systemic granulomatous disease, is a predominantly T-cell disease but evidence for a role for humoral immunity in disease pathogenesis is growing. Utilizing samples from the Genomic Research in Alpha-1 anti-trypsin Deficiency and Sarcoidosis (GRADS) study, we examined the prevalence of autoantibodies in sarcoidosis patients with pulmonary-only and extra-pulmonary organ involvement compared to normal controls.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Study design and methods<\/jats:title>\n<jats:p>We analyzed serum samples from sarcoidosis patients who participated in the GRADS study utilizing an autoantigen microarray platform for both IgM and IgG antibodies. The cohort included sarcoidosis patients with pulmonary-only disease (POS, n = 106), sarcoidosis patients with extra-pulmonary disease (EPS, n = 120) and a normal control cohort (NC, n = 101). Organ involvement was assessed following a standardized format across all GRADS participating centers.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Sarcoidosis patients overall had increased levels of IgM and IgG autoantibodies compared to normal controls. In addition, several autoantibodies were elevated in the POS and EPS cohorts compared to the NC cohort. Differences in autoantibody levels were also noted between the POS and the EPS cohorts. When comparing organ involvement with sarcoidosis, bone, spleen and ear, nose and throat involvement had higher IgM expression than other organs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Sarcoidosis patients have elevated IgM and IgG autoantibody levels compared to normal controls. In addition, individuals with pulmonary as well as additional organ involvement had higher IgM expression. Further research is needed focusing on specific organ-autoantibody pairs and role of autoantibodies in disease pathogenesis.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0274381","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T18:32:35Z","timestamp":1666290755000},"page":"e0274381","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Autoantibody profile in sarcoidosis, analysis from the GRADS sarcoidosis cohort"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2160-4498","authenticated-orcid":true,"given":"Basheer","family":"Khassawneh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengsong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Briana","family":"Barkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Vestal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Shrock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May","family":"Gillespie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Pacheco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Deane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Maier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan-Zhen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7296-8975","authenticated-orcid":true,"given":"Nabeel","family":"Hamzeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"GRADS investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"issue":"8","key":"pone.0274381.ref001","doi-asserted-by":"crossref","first-page":"e26","DOI":"10.1164\/rccm.202002-0251ST","article-title":"Diagnosis and Detection of Sarcoidosis. 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diseases","volume":"7","author":"Y Shoenfeld","year":"1989","journal-title":"Clinical and experimental rheumatology"},{"issue":"1","key":"pone.0274381.ref041","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00403-008-0895-5","article-title":"Drug-induced lupus erythematosus","volume":"301","author":"CD Vedove","year":"2009","journal-title":"Archives of dermatological research"},{"issue":"8","key":"pone.0274381.ref042","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1136\/ard.57.8.470","article-title":"Antigen specificity of antihistone antibodies in systemic sclerosis","volume":"57","author":"M Hasegawa","year":"1998","journal-title":"Ann Rheum Dis"},{"issue":"4","key":"pone.0274381.ref043","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.autrev.2013.11.009","article-title":"Diagnostic criteria of autoimmune hepatitis","volume":"13","author":"R Liberal","year":"2014","journal-title":"Autoimmunity 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