{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:15:10Z","timestamp":1790298910081,"version":"4.1.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"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":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CD40 is a costimulatory receptor on APCs that is critical for the induction and maintenance of humoral and cell-mediated immunity. Accordingly, CD40 and its ligand, CD40L, have long been considered targets for the treatment of autoimmune diseases. We developed a rat\/mouse chimeric anti-mouse CD40 antagonist mAb, 201A3, and evaluated its ability to alleviate murine lupus. Treatment of NZB\/W-F1 mice with 201A3 after the onset of severe proteinuria rapidly reversed established severe proteinuria and nephritis and largely restored normal glomerular and tubular morphology. This coincided with a normalization of the expression of genes associated with proteinuria and injury by kidney parenchymal cells. Anti-CD40 treatment also prevented and reversed loss of saliva production and sialadenitis. These effects on kidney and salivary gland function were confirmed using mice of a second strain, MRL\/Mp-lpr\/lpr, and extended to alleviating joint inflammation. Immunologically, anti-CD40 treatment disrupted multiple processes that contribute to the pathogenesis of systemic lupus erythematosus (SLE), including autoreactive B cell activation, T effector cell function in target tissues, and type I IFN production. This ability to disrupt disease-critical immunological mechanisms, to reverse glomerular and tubular injury at the cellular and gene expression levels, and to confer exceptional therapeutic efficacy suggests that CD40 is a central disease pathway in murine SLE. Thus, a CD40 antagonist Ab could be an effective therapeutic in the treatment of SLE.<\/jats:p>","DOI":"10.4049\/jimmunol.1900043","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T19:15:15Z","timestamp":1558379715000},"page":"58-75","source":"Crossref","is-referenced-by-count":39,"title":["Treatment with a CD40 Antagonist Antibody Reverses Severe Proteinuria and Loss of Saliva Production and Restores Glomerular Morphology in Murine Systemic Lupus Erythematosus"],"prefix":"10.1093","volume":"203","author":[{"given":"Stuart J","family":"Perper","sequence":"first","affiliation":[{"name":"AbbVie Bioresearch Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan V","family":"Westmoreland","sequence":"additional","affiliation":[{"name":"AbbVie Bioresearch Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozsef","family":"Karman","sequence":"additional","affiliation":[{"name":"AbbVie Bioresearch Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Twomey","sequence":"additional","affiliation":[{"name":"AbbVie Bioresearch Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5959-5139","authenticated-orcid":false,"given":"Jane","family":"Seagal","sequence":"additional","affiliation":[{"name":"AbbVie Bioresearch Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"AbbVie Bioresearch Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradford L","family":"McRae","sequence":"additional","affiliation":[{"name":"AbbVie Bioresearch Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H","family":"Clarke","sequence":"additional","affiliation":[{"name":"AbbVie Bioresearch Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"2025030418132994100_r1","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1002\/art.1780400928","article-title":"Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus","volume":"40","author":"Hochberg","year":"1997","journal-title":"Arthritis Rheum."},{"key":"2025030418132994100_r2","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.autrev.2014.10.003","article-title":"A volcanic explosion of autoantibodies in systemic lupus erythematosus: a diversity of 180 different antibodies found in SLE patients","volume":"14","author":"Yaniv","year":"2015","journal-title":"Autoimmun. 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