{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:22:19Z","timestamp":1790486539259,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,2,3]],"date-time":"2005-02-03T00:00:00Z","timestamp":1107388800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2005,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Cross\u2010reactivity with kidney antigens is believed to be a critical determinant in the renal pathogenicity of anti\u2013double\u2010stranded DNA (anti\u2010dsDNA) antibodies. Murine nephritogenic anti\u2010dsDNA antibodies have been shown to cross\u2010react with \u03b1\u2010actinin, and anti\u2013\u03b1\u2010actinin antibodies have been found to be deposited in the kidneys of lupus mice with active nephritis. Furthermore, in humans with systemic lupus erythematosus (SLE), it has been found that a greater proportion of polyclonal IgG anti\u2010dsDNA antibodies from patients with renal involvement bind to \u03b1\u2010actinin than do those from patients without renal disease. We undertook this study to substantiate a direct link between cross\u2010reactive anti\u2010dsDNA\/anti\u2013\u03b1\u2010actinin antibodies and the pathogenesis of lupus nephritis in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A panel of 10 anti\u2010dsDNA and\/or anti\u2013\u03b1\u2010actinin antibodies was generated by Epstein\u2010Barr virus transformation of lymphocytes from patients with SLE and was extensively characterized. Antibody binding was studied by enzyme\u2010linked immunosorbent assay and Western blotting. Antibody potential for pathogenicity was assessed by measuring binding to isolated glomeruli and mesangial cells and by evaluation of histologic features of the kidney following injection in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All anti\u2010dsDNA antibodies isolated also bound \u03b1\u2010actinin. Cross\u2010reactive antibodies bound to mesangial cells and to isolated glomeruli ex vivo. Binding to glomeruli was not inhibited by DNase treatment, but could be abrogated by \u03b1\u2010actinin. Furthermore, histopathologic abnormalities seen in mice injected intraperitoneally with a cross\u2010reactive cell line included fusion of podocyte foot processes and subepithelial and subendothelial deposition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These studies provide strong support for the hypothesis that \u03b1\u2010actinin is a major cross\u2010reactive target for anti\u2010dsDNA antibodies in SLE patients. Cross\u2010reactive anti\u2010dsDNA\/anti\u2013\u03b1\u2010actinin antibodies from SLE patients are pathogenic and may contribute to the kidney lesions in lupus nephritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20862","type":"journal-article","created":{"date-parts":[[2005,2,3]],"date-time":"2005-02-03T22:49:16Z","timestamp":1107470956000},"page":"522-530","source":"Crossref","is-referenced-by-count":101,"title":["Cross\u2010reactivity of human lupus anti\u2010DNA antibodies with \u03b1\u2010actinin and nephritogenic potential"],"prefix":"10.1002","volume":"52","author":[{"given":"Zeguo","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Weinstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Tuzova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Mundel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Marambio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaim","family":"Putterman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,2,3]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.5.435"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V102413"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199805073381906"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200104)31:4<1221::AID-IMMU1221>3.0.CO;2-P"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.6.3072"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20103"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780251101"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118952"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118666"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119796"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390605"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.5.1797"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.4.1317"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118924"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000014223.71109.13"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/030097498441182"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s000110050718"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1568-9972(03)00082-X"},{"key":"e_1_2_5_20_2","first-page":"C184","article-title":"A pathogenic anti\u2010DNA antibody upregulates NOS and c\u2010fos expression in lupus glomerular mesangial cells","volume":"17","author":"Qing X","year":"2003","journal-title":"FASEB J"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199801)28:01<339::AID-IMMU339>3.0.CO;2-C"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1995.341"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1994.tb06607.x"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031519"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0300-9475.2004.01463.x"},{"key":"e_1_2_5_26_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_5_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11092"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(80)90169-2"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.3109\/03009748309098535"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.56.11.661"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.52.1.14"}],"container-title":["Arthritis &amp; 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