{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:24:28Z","timestamp":1791465868588,"version":"4.3.4"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T00:00:00Z","timestamp":1312156800000},"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; Rheumatism"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Numerous observations implicate interferon\u2010\u03b1 (IFN\u03b1) in the pathophysiology of systemic lupus erythematosus (SLE); however, the potential impact of endogenous anti\u2010IFN\u03b1 autoantibodies (AIAAs) on IFN\u2010pathway and disease activity is unclear. The aim of this study was to characterize IFN\u2010pathway activity and the serologic and clinical profiles of AIAA\u2010positive patients with SLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sera obtained from patients with SLE (n = 49), patients with rheumatoid arthritis (n = 25), and healthy control subjects (n = 25) were examined for the presence of AIAAs, using a biosensor immunoassay. Serum type I IFN bioactivity and the ability of AIAA\u2010positive sera to neutralize IFN\u03b1 activity were determined using U937 cells. Levels of IFN\u2010regulated gene expression in peripheral blood were determined by microarray, and serum levels of BAFF, IFN\u2010inducible chemokines, and other autoantibodies were measured using immunoassays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AIAAs were detected in 27% of the serum samples from patients with SLE, using a biosensor immunoassay. Unsupervised hierarchical clustering analysis identified 2 subgroups of patients, IFN<jats:sup>low<\/jats:sup> and IFN<jats:sup>high<\/jats:sup>, that differed in the levels of serum type I IFN bioactivity, IFN\u2010regulated gene expression, BAFF, anti\u2013ribosomal P, and anti\u2010chromatin autoantibodies, and in AIAA status. The majority of AIAA\u2010positive patients had significantly lower levels of serum type I IFN bioactivity, reduced downstream IFN\u2010pathway activity, and lower disease activity compared with the IFN<jats:sup>high<\/jats:sup> patients. AIAA\u2010positive sera were able to effectively neutralize type I IFN activity in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with SLE commonly harbor AIAAs. AIAA\u2010positive patients have lower levels of serum type I IFN bioactivity and evidence for reduced downstream IFN\u2010pathway and disease activity. AIAAs may influence the clinical course in SLE by blunting the effects produced by IFN\u03b1.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.30399","type":"journal-article","created":{"date-parts":[[2011,4,20]],"date-time":"2011-04-20T11:39:50Z","timestamp":1303299590000},"page":"2407-2415","source":"Crossref","is-referenced-by-count":114,"title":["Association of endogenous anti\u2013interferon\u2010\u03b1 autoantibodies with decreased interferon\u2010pathway and disease activity in patients with systemic lupus erythematosus"],"prefix":"10.1002","volume":"63","author":[{"given":"Alyssa M.","family":"Morimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna Thibault","family":"Flesher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Wolslegel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Brady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander R.","family":"Abbas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Quarmby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Wakshull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Townsend","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy W.","family":"Behrens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,8]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2004.00204.x"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21571"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780250406"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6176024"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1064890"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1191\/096120300674499064"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.033753"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21031"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21890"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19911001)68:7<1536::AID-CNCR2820680713>3.0.CO;2-B"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830410215"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0337679100"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021553"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11226"},{"issue":"10","key":"e_1_2_8_16_2","first-page":"S775","article-title":"Dose\u2010dependent modulation of interferon regulated genes with administration of single and repeat doses of rontalizumab in a phase I, placebo controlled, double blind, dose escalation study in SLE","volume":"60","author":"McBride JM","year":"2009","journal-title":"Arthritis Rheum"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24557"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780251101"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2004.06.002"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.25.14863"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth349"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350606"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1159\/000076746"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.11.7467"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1089\/107999099313901"},{"key":"e_1_2_8_27_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4049\/jimmunol.129.1.1","article-title":"Antibodies to \u03b1\u2010interferon in a patient with systemic lupus erythematosus","volume":"129","author":"Panem S","year":"1982","journal-title":"J Immunol"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780280605"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00269199"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1089\/107999003321532475"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni829"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510837103"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.11.1697"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1177\/0961203309105529"},{"key":"e_1_2_8_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11354"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.30399","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.30399","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T10:34:11Z","timestamp":1700735651000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.30399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8]]},"references-count":34,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2011,8]]}},"alternative-id":["10.1002\/art.30399"],"URL":"https:\/\/doi.org\/10.1002\/art.30399","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,8]]}}}