{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:22:26Z","timestamp":1790965346077,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,3,30]],"date-time":"2011-03-30T00:00:00Z","timestamp":1301443200000},"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":[[2011,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Complement has both protective and pathogenic functions in lupus due to a balance between its role in the clearance of immune complexes (ICs) and apoptotic cells and its role in inflammation. The classical pathway contributes to IC and apoptotic cell clearance, whereas the alternative pathway is a key mediator of renal inflammation. The aim of this study was to investigate the effect of a new targeted inhibitor of the alternative pathway, CR2\u2010fH, on lupus\u2010like renal disease in MRL\/<jats:italic>lpr<\/jats:italic> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice were treated with either saline, CR2\u2010fH, CR2\u2010Crry (which inhibits all complement pathways), or soluble CR2 (sCR2; C3d\u2010binding targeting vehicle). Sera were analyzed every 2 weeks for autoantibodies, circulating ICs, and C3. Urinary excretion of albumin was also determined, and kidneys were collected at 23 weeks for histologic evaluation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment with CR2\u2010fH or CR2\u2010Crry improved survival and significantly reduced proteinuria, glomerular C3 deposition, and the level of circulating ICs. CR2\u2010fH, but not CR2\u2010Crry, also significantly reduced glomerulonephritis, expression of serum anti\u2013double\u2010stranded DNA (anti\u2010dsDNA) antibodies, and glomerular IgG and C1q deposition. Interestingly, sCR2 also significantly reduced the levels of anti\u2010dsDNA antibodies and circulating ICs and reduced glomerular deposition of IgG, C1q, and C3, although there was no significant reduction in glomerulonephritis, proteinuria, or mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Targeted and selective inhibition of the alternative complement pathway is an effective treatment of murine lupus and is more effective than blockade of all pathways. The data demonstrate benefits to leaving the classical\/lectin pathways intact and indicate distinct roles for the classical and alternative pathways of complement in disease progression. The sCR2\u2010targeting vehicle contributes to therapeutic activity, possibly via modulation of autoimmunity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.30222","type":"journal-article","created":{"date-parts":[[2011,1,10]],"date-time":"2011-01-10T16:42:04Z","timestamp":1294677724000},"page":"1076-1085","source":"Crossref","is-referenced-by-count":77,"title":["The benefit of targeted and selective inhibition of the alternative complement pathway for modulating autoimmunity and renal disease in MRL\/<i>lpr<\/i> mice"],"prefix":"10.1002","volume":"63","author":[{"given":"Hideharu","family":"Sekine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting Ting Hsieh","family":"Kinser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efrain","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Paulling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary S.","family":"Gilkeson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Tomlinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,3,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2006.09.009"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.6.3913"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81108-3"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200104053441406"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.3109\/08830189309051170"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(01)76021-X"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0598-56"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.5.2538"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.3.1036"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.012703.104549"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2009.11.014"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60342-9"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.2.786"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00371.x"},{"key":"e_1_2_6_16_2","doi-asserted-by":"crossref","first-page":"4553","DOI":"10.4049\/jimmunol.160.9.4553","article-title":"Blockade of antibody\u2010induced glomerulonephritis with Crry\u2010Ig, a soluble murine complement inhibitor","volume":"160","author":"Quigg RJ","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.2.1231"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.16.8563"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.10.6444"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.11.8068"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25208"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.10.7423"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.143.1.103"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.157.2.549"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390605"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.148.5.1198"},{"key":"e_1_2_6_27_2","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.4049\/jimmunol.139.10.3287","article-title":"Polyreactive autoantibodies are nephritogenic in murine lupus nephritis","volume":"139","author":"Pankewycz OG","year":"1987","journal-title":"J Immunol"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108626"},{"key":"e_1_2_6_29_2","first-page":"1763","article-title":"Arteritis in a novel congenic strain of mice derived from MRL\/Lpr lupus mice: genetic dissociation from glomerulonephritis and limited autoantibody production","volume":"149","author":"Nose M","year":"1996","journal-title":"Am J Pathol"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.1.151"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012733360-1\/50029-4"},{"key":"e_1_2_6_32_2","first-page":"163","volume-title":"Complement in health and disease","author":"Whaley K","year":"1987"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000051597.27127.A1"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1159\/000075686"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1080\/08916930410001685063"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00228-X"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.1.383"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021996"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.bor.0000135453.70424.1b"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.3.2134"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350907"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350109"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1979.156"},{"key":"e_1_2_6_44_2","first-page":"11","article-title":"Activation of the alternative complement pathway in systemic lupus erythematosus","volume":"26","author":"Wilson MR","year":"1976","journal-title":"Clin Exp Immunol"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.81"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2004.02525.x"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.30222","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.30222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T08:47:13Z","timestamp":1700729233000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.30222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,30]]},"references-count":45,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2011,4]]}},"alternative-id":["10.1002\/art.30222"],"URL":"https:\/\/doi.org\/10.1002\/art.30222","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,3,30]]}}}