{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T20:37:57Z","timestamp":1775075877881,"version":"3.50.1"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003793","name":"Swedish Heart-Lung Foundation","doi-asserted-by":"publisher","award":["20170664"],"award-info":[{"award-number":["20170664"]}],"id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003793","name":"Swedish Heart-Lung Foundation","doi-asserted-by":"publisher","award":["20200506"],"award-info":[{"award-number":["20200506"]}],"id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2018-02884"],"award-info":[{"award-number":["2018-02884"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2019-01034"],"award-info":[{"award-number":["2019-01034"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Sarcoidosis is an inflammatory disease that affects multiple organs. Cell analysis from bronchoalveolar lavage fluid (BALF) is a valuable tool in the diagnostic workup and differential diagnosis of sarcoidosis. Besides the expansion of lymphocyte expression-specific receptor segments (V\u03b12.3 and V\u03b222) in some patients with certain HLA types, the relation between sarcoidosis susceptibility and BAL cell populations\u2019 quantitative levels is not well-understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Quantitative levels defined by cell concentrations of BAL cells and CD4<jats:sup>+<\/jats:sup>\/CD8<jats:sup>+<\/jats:sup> ratio were evaluated together with genetic variants associated with sarcoidosis in 692 patients with extensive clinical data. Genetic variants associated with clinical phenotypes, L\u00f6fgren\u2019s syndrome (LS) and non-L\u00f6fgren\u2019s syndrome (non-LS), were examined separately. An association test <jats:italic>via<\/jats:italic> linear regression using an additive model adjusted for sex, age, and correlated cell type was applied. To infer the biological function of genetic associations, enrichment analysis of expression quantitative trait (eQTLs) across publicly available eQTL databases was conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Multiple genetic variants associated with sarcoidosis were significantly associated with quantitative levels of BAL cells. Specifically, LS genetic variants, mainly from the HLA locus, were associated with quantitative levels of BAL macrophages, lymphocytes, CD3<jats:sup>+<\/jats:sup> cells, CD4<jats:sup>+<\/jats:sup> cells, CD8<jats:sup>+<\/jats:sup> cells, CD4<jats:sup>+<\/jats:sup>\/CD8<jats:sup>+<\/jats:sup> ratio, neutrophils, basophils, and eosinophils. Non-LS genetic variants were associated with quantitative levels of BAL macrophages, CD8<jats:sup>+<\/jats:sup> cells, basophils, and eosinophils. eQTL enrichment revealed an influence of sarcoidosis-associated SNPs and regulation of gene expression in the lung, blood, and immune cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Genetic variants associated with sarcoidosis are likely to modulate quantitative levels of BAL cell types and may regulate gene expression in immune cell populations. Thus, the role of sarcoidosis-associated gene-variants may be to influence cellular phenotypes underlying the disease immunopathology.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2023.1061654","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T09:44:23Z","timestamp":1675763063000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Functional link between sarcoidosis-associated gene variants and quantitative levels of bronchoalveolar lavage fluid cell types"],"prefix":"10.3389","volume":"10","author":[{"given":"Muntasir","family":"Abo Al Hayja","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Kullberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Eklund","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonid","family":"Padyukov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"Grunewald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia V.","family":"Rivera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41572-019-0096-x","article-title":"Sarcoidosis","volume":"5","author":"Grunewald","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1034\/j.1399-3003.1999.14d02.x","article-title":"ATS\/ERS\/WASOG statement on sarcoidosis. 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