{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:35:12Z","timestamp":1790523312694,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,3,19]],"date-time":"2014-03-19T00:00:00Z","timestamp":1395187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Tissue Antigens"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Genetic factors influence the risk for disease as well as the clinical picture seen in sarcoidosis and especially the genes localized to the human leukocyte antigen (<jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>) region on chromosome 6 are of importance. The aim of this study was to further investigate associations between <jats:styled-content style=\"fixed-case\">HLA\u2010DRB1<\/jats:styled-content> alleles and the risk for extra\u2010pulmonary manifestations (EPMs), i.e. engagement of the skin, superficial lymph nodes, eyes, nervous system, kidneys, hypercalcemia, parotid and salivary glands, heart, liver, spleen and bone marrow in Scandinavian sarcoidosis patients. One thousand patients with together with a group of 2000 healthy individuals, matched for sex and age. <jats:styled-content style=\"fixed-case\">HLA\u2010DRB1<\/jats:styled-content> alleles were determined for all patients and controls. Excluding erythema nodosum and ankle arthritis, we found 288 of 1000 patients to have <jats:styled-content style=\"fixed-case\">EPMs<\/jats:styled-content>. There were 383 patients with L\u00f6fgren's syndrome (<jats:styled-content style=\"fixed-case\">LS<\/jats:styled-content>), and among them <jats:styled-content style=\"fixed-case\">EPM<\/jats:styled-content> were relatively uncommon and diagnosed in only 31 (8.1%) of the patients. In contrast, among the 617 non\u2010<jats:styled-content style=\"fixed-case\">LS<\/jats:styled-content> patients, 257 (41.6%) had <jats:styled-content style=\"fixed-case\">EPM<\/jats:styled-content> (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). In <jats:styled-content style=\"fixed-case\">LS<\/jats:styled-content> patients, the absence of <jats:italic><jats:styled-content style=\"fixed-case\">HLA\u2010DRB1<\/jats:styled-content>*03<\/jats:italic> substantially increased the risk factor for <jats:styled-content style=\"fixed-case\">EPM<\/jats:styled-content> (erythema nodosum and ankle arthritis excluded) (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). A distinct <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content> allele combination, <jats:italic><jats:styled-content style=\"fixed-case\">HLA\u2010DRB1<\/jats:styled-content>*04\/*15<\/jats:italic>, was identified as a risk factor for <jats:styled-content style=\"fixed-case\">EPM<\/jats:styled-content> in all patients (25 of 50 with <jats:italic><jats:styled-content style=\"fixed-case\">DRB1<\/jats:styled-content>*04\/15<\/jats:italic> had <jats:styled-content style=\"fixed-case\">EPM<\/jats:styled-content>). In conclusion,  <jats:styled-content style=\"fixed-case\">EPM<\/jats:styled-content> are common in non\u2010<jats:styled-content style=\"fixed-case\">LS<\/jats:styled-content> sarcoidosis. Furthermore, <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010typing of sarcoidosis patients can be used in the clinic to identify patients with an increased risk for <jats:styled-content style=\"fixed-case\">EPM<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/tan.12326","type":"journal-article","created":{"date-parts":[[2014,3,19]],"date-time":"2014-03-19T06:35:40Z","timestamp":1395210940000},"page":"267-272","source":"Crossref","is-referenced-by-count":35,"title":["<scp>HLA<\/scp>\u2010alleles associated with increased risk for extra\u2010pulmonary involvement in sarcoidosis"],"prefix":"10.1111","volume":"83","author":[{"given":"P.","family":"Darlington","sequence":"first","affiliation":[{"name":"Respiratory Medicine Unit, Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"},{"name":"Respiratory Medicine Unit, Department of Medicine Karolinska Institutet and S\u00f6dersjukhuset Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Gabrielsen","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"S\u00f6rensson","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Tallstedt","sequence":"additional","affiliation":[{"name":"Karolinska Institutet and St. Erik Eye Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Padyukov","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Medicine Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Eklund","sequence":"additional","affiliation":[{"name":"Respiratory Medicine Unit, Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Grunewald","sequence":"additional","affiliation":[{"name":"Respiratory Medicine Unit, Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,3,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra071714"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/353622a0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200807-1082OC"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.161.3.9906001"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.151.1.7812546"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq325"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.2.ats4-99"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00025011"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/09273940902818861"},{"key":"e_1_2_7_11_1","first-page":"23","volume-title":"Guideline for Diagnosis of Cardiac Sarcoidosis: Study Report on Diffuse Pulmonary Diseases","author":"Hiraga H","year":"1993"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/92.2.103"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1993.tb01991.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2370.1999.00173.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.44.1.125"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.2.7633707"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2011.10.016"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/sarh.2002.32552"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10251"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2005.10.024"},{"key":"e_1_2_7_21_1","first-page":"66","article-title":"Clinical course of sarcoidosis in dependence on HLA\u2010DRB1 allele frequencies, inflammatory markers, and the presence of M. tuberculosis DNA fragments","volume":"22","author":"Grosser M","year":"2005","journal-title":"Sarcoidosis Vasc Diffuse Lung Dis"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.12.8784"},{"key":"e_1_2_7_23_1","first-page":"1134","article-title":"The role of HLA class II genes in insulin\u2010dependent diabetes mellitus: molecular analysis of 180 Caucasian, multiplex families","volume":"59","author":"Noble JA","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201006-0865CI"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200303-459OC"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.2007.00904.x"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-101532"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1586\/eci.13.8"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.10"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.93"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.192.1.8208972"}],"container-title":["Tissue Antigens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ftan.12326","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/tan.12326","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T23:16:04Z","timestamp":1696029364000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/tan.12326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,19]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,4]]}},"alternative-id":["10.1111\/tan.12326"],"URL":"https:\/\/doi.org\/10.1111\/tan.12326","archive":["Portico"],"relation":{},"ISSN":["0001-2815","1399-0039"],"issn-type":[{"value":"0001-2815","type":"print"},{"value":"1399-0039","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,19]]}}}