{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T01:00:52Z","timestamp":1778806852721,"version":"3.51.4"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2003,6,3]],"date-time":"2003-06-03T00:00:00Z","timestamp":1054598400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI-42183"],"award-info":[{"award-number":["AI-42183"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2003,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Human C\u2010reactive protein (CRP) binds apoptotic cells and alters blood clearance of injected chromatin in mice. To test whether CRP participates in the pathogenesis of systemic lupus erythematosus (SLE), we examined disease development in lupus\u2010prone (NZB \u00d7 NZW)F<jats:sub>1<\/jats:sub> (NZB\/NZW) mice expressing a human CRP transgene (hCRPtg\/BW).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mortality was monitored, proteinuria was determined by dipstick, and serum levels of human CRP and anti\u2013double\u2010stranded DNA (anti\u2010dsDNA) were determined by enzyme\u2010linked immunosorbent assay in NZB\/NZW and hCRPtg\/BW mice. Thin sections of kidneys were analyzed by immunofluorescence microscopy to compare deposition of IgG, IgM, C3, and human CRP, and electron microscopy was used to reveal differences in ultrastructure. In situ hybridization was performed to detect human CRP messenger RNA expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The hCRPtg\/BW mice had less proteinuria and longer survival than NZB\/NZW mice. They also had lower IgM and higher IgG anti\u2010dsDNA titers than NZB\/NZW mice, although the differences were transient and small. In hCRPtg\/BW mice, accumulation of IgM and IgG in the renal glomeruli was delayed, reduced, and more mesangial than in NZB\/NZW mice, while end\u2010stage accumulation of IgG, IgM, and C3 in the renal cortex was prevented. There was less glomerular podocyte fusion, basement membrane thickening, mesangial cell proliferation, and occlusion of capillary lumens in hCRPtg\/BW mice, but dense deposits in the mesangium were increased. With disease progression in hCRPtg\/BW mice, there was little rise in the plasma CRP level, but CRP in the kidneys became increasingly apparent due to local, disease\u2010independent, age\u2010related expression of the transgene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In hCRPtg\/BW mice, CRP protects against SLE by increasing blood and mesangial clearance of immune complexes and by preventing their accumulation in the renal cortex.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.11026","type":"journal-article","created":{"date-parts":[[2003,6,4]],"date-time":"2003-06-04T10:07:16Z","timestamp":1054721236000},"page":"1602-1611","source":"Crossref","is-referenced-by-count":79,"title":["Delayed lupus onset in (NZB \u00d7 NZW)F<sub>1<\/sub> mice expressing a human C\u2010reactive protein transgene"],"prefix":"10.1002","volume":"48","author":[{"given":"Alexander J.","family":"Szalai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casey T.","family":"Weaver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"McCrory","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederik W.","family":"van Ginkel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachael M.","family":"Reiman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John F.","family":"Kearney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony N.","family":"Marion","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John E.","family":"Volanakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,6,3]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"1319","volume-title":"Arthritis and allied conditions: a textbook of rheumatology","author":"Wallace DJ","year":"1997"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.52.1.63"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/197197a0"},{"key":"e_1_2_6_5_2","first-page":"121","volume-title":"Animal models of disease","author":"Theofilopoulos AN","year":"1989"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.16.1.261"},{"key":"e_1_2_6_7_2","first-page":"313","article-title":"C\u2010reactive protein and the acute phase response","volume":"37","author":"Ballou SP","year":"1992","journal-title":"Adv Intern Med"},{"key":"e_1_2_6_8_2","first-page":"815","article-title":"Absence of correlation between interleukin\u20106 and C\u2010reactive protein blood levels in systemic lupus erythematosus compared with rheumatoid arthritis","volume":"20","author":"Gabay C","year":"1993","journal-title":"J Rheumatol"},{"key":"e_1_2_6_9_2","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0307-742X(21)00201-0","article-title":"C\u2010reactive protein in SLE","volume":"8","author":"Pepys MB","year":"1982","journal-title":"Clin Rheum Dis"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230609"},{"key":"e_1_2_6_11_2","doi-asserted-by":"crossref","first-page":"4266","DOI":"10.4049\/jimmunol.141.12.4266","article-title":"Analysis of the binding of C\u2010reactive protein to histones and chromatin","volume":"141","author":"Du Clos TW","year":"1988","journal-title":"J Immunol"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1993.1035"},{"key":"e_1_2_6_13_2","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.4049\/jimmunol.143.8.2553","article-title":"C\u2010reactive protein reacts with the U1 small nuclear ribonucleoprotein","volume":"143","author":"Du Clos TW","year":"1989","journal-title":"J Immunol"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.161.6.1344"},{"key":"e_1_2_6_15_2","first-page":"2135","article-title":"Interaction of C\u2010reactive protein complexes with the complement system. 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