{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:54:57Z","timestamp":1790704497512,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T00:00:00Z","timestamp":1312156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The critical role of IFN-\u03b1 in the pathogenesis of human systemic lupus erythematosus has been highlighted in recent years. Exposure of young lupus-prone NZB\/W F1 mice to IFN-\u03b1 in vivo leads to an accelerated lupus phenotype that is dependent on T cells and is associated with elevated serum levels of BAFF, IL-6, and TNF-\u03b1, increased splenic expression of IL-6 and IL-21, formation of large germinal centers, and the generation of large numbers of short-lived plasma cells that produce IgG2a and IgG3 autoantibodies. In this study, we show that both IgG2a and IgG3 autoantibodies are pathogenic in IFN-\u03b1\u2013accelerated lupus, and their production can be dissociated by using low-dose CTLA4-Ig. Only high-dose CTLA4-Ig attenuates both IgG2a and IgG3 autoantibody production and significantly delays death from lupus nephritis. In contrast, BAFF\/APRIL blockade has no effect on germinal centers or the production of IgG anti-dsDNA Abs but, if given at the time of IFN-\u03b1 challenge, delays the progression of lupus by attenuating systemic and renal inflammation. Temporary remission of nephritis induced by combination therapy with cyclophosphamide, anti-CD40L Ab, and CTLA4-Ig is associated with the abrogation of germinal centers and depletion of short-lived plasma cells, but relapse occurs more rapidly than in conventional NZB\/W F1 mice. This study demonstrates that IFN-\u03b1 renders NZB\/W F1 relatively resistant to therapeutic intervention and suggests that the IFN signature should be considered when randomizing patients into groups and analyzing the results of human clinical trials in systemic lupus erythematosus.<\/jats:p>","DOI":"10.4049\/jimmunol.1004142","type":"journal-article","created":{"date-parts":[[2011,6,25]],"date-time":"2011-06-25T23:17:02Z","timestamp":1309043822000},"page":"1506-1513","source":"Crossref","is-referenced-by-count":48,"title":["IFN-\u03b1 Confers Resistance of Systemic Lupus Erythematosus Nephritis to Therapy in NZB\/W F1 Mice"],"prefix":"10.1093","volume":"187","author":[{"given":"Zheng","family":"Liu","sequence":"first","affiliation":[{"name":"Center for Autoimmunity and Musculoskeletal Diseases, Feinstein Institute for Medical Research , Manhasset, New York, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramalingam","family":"Bethunaickan","sequence":"additional","affiliation":[{"name":"Center for Autoimmunity and Musculoskeletal Diseases, Feinstein Institute for Medical Research , Manhasset, New York, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqing","family":"Huang","sequence":"additional","affiliation":[{"name":"Center for Autoimmunity and Musculoskeletal Diseases, Feinstein Institute for Medical Research , Manhasset, New York, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meera","family":"Ramanujam","sequence":"additional","affiliation":[{"name":"Center for Autoimmunity and Musculoskeletal Diseases, Feinstein Institute for Medical Research , Manhasset, New York, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P","family":"Madaio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical College of Georgia , Augusta, GA 30912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Davidson","sequence":"additional","affiliation":[{"name":"Center for Autoimmunity and Musculoskeletal Diseases, Feinstein Institute for Medical Research , Manhasset, New York, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,8,1]]},"reference":[{"key":"2025032410234086300_r1","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1136\/ard.2010.135186","article-title":"Therapeutic opportunities in systemic lupus erythematosus: state of the art and prospects for the new decade","volume":"69","author":"Bertsias","year":"2010","journal-title":"Ann. 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