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In cells expressing LINE<\/jats:styled-content>\u20101, these proteins assemble with LINE<\/jats:styled-content>\u20101 RNA<\/jats:styled-content> and additional RNA<\/jats:styled-content> binding proteins, some of which are well\u2010known autoantigens in patients with systemic lupus erythematosus (SLE<\/jats:styled-content>). This study was undertaken to investigate whether SLE<\/jats:styled-content> patients also produce autoantibodies against LINE<\/jats:styled-content>\u20101 p40.<\/jats:p><\/jats:sec>Methods<\/jats:title>Highly purified p40 protein was used to quantitate IgG autoantibodies in serum from 172 SLE<\/jats:styled-content> patients and from disease controls and age\u2010matched healthy subjects by immunoblotting and enzyme\u2010linked immunosorbent assay (ELISA<\/jats:styled-content>). Preparations of p40 that also contained associated proteins were analyzed by immunoblotting with patient sera.<\/jats:p><\/jats:sec>Results<\/jats:title>Antibodies reactive with p40 were detected in the majority of patients and many healthy controls. Their levels were higher in patients with SLE<\/jats:styled-content>, but not those with systemic sclerosis, compared to healthy subjects (P<\/jats:italic> = 0.01). Anti\u2010p40 reactivity was higher in patients during a flare than in patients with disease in remission (P<\/jats:italic> = 0.03); correlated with the SLE<\/jats:styled-content> Disease Activity Index score (P<\/jats:italic> = 0.0002), type I interferon score (P<\/jats:italic> = 0.006), decrease in complement C3 level (P<\/jats:italic> = 0.0001), the presence of anti\u2010DNA<\/jats:styled-content> antibodies (P<\/jats:italic> < 0.0001) and anti\u2010C1q antibodies (P<\/jats:italic> = 0.004), and current or past history of nephritis (P<\/jats:italic> = 0.02 and P<\/jats:italic> = 0.003, respectively); and correlated inversely with age (r = \u22120.49, P<\/jats:italic> < 0.0001). SLE<\/jats:styled-content> patient sera also reacted with p40\u2010associated proteins.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Autoantibodies reacting with LINE<\/jats:styled-content>\u20101 p40 characterize a population of SLE<\/jats:styled-content> patients with severe and active disease. These autoantibodies may represent an early immune response against LINE<\/jats:styled-content>\u20101 p40 that does not yet by itself imply clinically significant autoimmunity, but may represent an early, and still reversible, step toward SLE<\/jats:styled-content> pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41054","type":"journal-article","created":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T02:19:06Z","timestamp":1564021146000},"page":"89-99","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["High Prevalence and Disease Correlation of Autoantibodies Against p40 Encoded by Long Interspersed Nuclear Elements in Systemic Lupus Erythematosus"],"prefix":"10.1002","volume":"72","author":[{"given":"Victoria","family":"Carter","sequence":"first","affiliation":[{"name":"University of Washington 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