{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:18:38Z","timestamp":1791389918373,"version":"4.3.3"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2002,8,1]],"date-time":"2002-08-01T00:00:00Z","timestamp":1028160000000},"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":[[2002,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The signature lesion of autoantibody-associated congenital heart block (CHB) is fibrosis of the conducting tissue. To date, participation of myofibroblasts in the cascade to injury has been unexplored. The importance of myofibroblast\/macrophage cross-talk is demonstrated by the novel finding of these cell types in the heart of a neonate dying of CHB. This clue to pathogenesis prompted consideration of the mechanism by which maternal anti-SSA\/Ro-SSB\/La Abs initiate an inflammatory response and promote fibrosis. Isolated cardiocytes from 16\u201324 wk abortuses were rendered apoptotic by exposure to poly (2-) hydroxyethylmethacrylate; flow cytometry confirmed surface expression of Ro\/La. Apoptotic cardiocytes were incubated with affinity-purified Abs to 52 and 60 kDa Ro from CHB mothers (opsonized) or IgG fractions from healthy donors (nonopsonized). Macrophages cultured with opsonized apoptotic cardiocytes expressed proinflammatory markers, supported by a three-fold increase in active \u03b1V\u03b23 integrin. Fetal cardiac fibroblasts exposed to supernatants obtained from macrophages incubated with opsonized apoptotic cardiocytes (but not nonopsonized) dramatically increased expression of the myofibroblast marker \u03b1-smooth muscle actin (SMAc). The \u201copsonized\u201d supernatant reversed an inhibitory effect of the \u201cnonopsonized\u201d supernatant on proliferation of fibroblasts (120 vs 69%, p &amp;lt; 0.05). Parallel experiments examined the effects of two cytokines and their neutralizing Abs on fibroblasts. TGF\u03b21 increased SMAc staining but decreased proliferation. TNF-\u03b1 did not affect either readout. Addition of anti-TGF\u03b21 Abs to the \u201copsonized\u201d supernatant blocked SMAc expression but increased proliferation, while anti-TNF-\u03b1 blocking Abs had no effects. These data suggest that transdifferentiation of cardiac fibroblasts to a scarring phenotype is a pathologic process initiated by maternal Abs.<\/jats:p>","DOI":"10.4049\/jimmunol.169.4.2156","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:19:11Z","timestamp":1398032351000},"page":"2156-2163","source":"Crossref","is-referenced-by-count":83,"title":["Transdifferentiation of Cardiac Fibroblasts, a Fetal Factor in Anti-SSA\/Ro-SSB\/La Antibody-Mediated Congenital Heart Block"],"prefix":"10.1093","volume":"169","author":[{"given":"Robert M","family":"Clancy","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine , New York, NY 10003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca D","family":"Askanase","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine , New York, NY 10003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj P","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Laboratories, Children\u2019s Hospital and Regional Medical Center, University of Washington , Seattle, WA 98105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstathia","family":"Chiopelas","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine , New York, NY 10003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Azar","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine , New York, NY 10003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Eugenia","family":"Miranda-Carus","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine , New York, NY 10003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill P","family":"Buyon","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine , New York, NY 10003"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2002,8,15]]},"reference":[{"key":"2025032905534672200_R1","first-page":"337","volume-title":"Systemic Lupus Erythematosus","year":"1999"},{"key":"2025032905534672200_R2","first-page":"5886","volume-title":"J. 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