{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:29:08Z","timestamp":1788305348954,"version":"build-2803163510"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"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":[[2019,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Given that diseases associated with anti-SSA\/Ro autoantibodies, such as systemic lupus erythematosus and Sj\u00f6gren syndrome, are linked with an upregulation of IFN and type I IFN\u2013stimulated genes, including sialic acid\u2013binding Ig-like lectin 1 (Siglec-1), a receptor on monocytes\/macrophages, recent attention has focused on a potential role for IFN and IFN-stimulated genes in the pathogenesis of congenital heart block (CHB). Accordingly, three approaches were leveraged to address the association of IFN, IFN-stimulated genes, and the phenotype of macrophages in affected fetal cardiac tissue: 1) cultured healthy human macrophages transfected with hY3, an anti-SSA\/Ro\u2013associated ssRNA, 2) RNA isolated from freshly sorted human leukocytes\/macrophages after Langendorff perfusion of three fetal hearts dying with CHB and three healthy gestational age-matched hearts, and 3) autopsy tissue from three additional human CHB hearts and one healthy heart. TLR ligation of macrophages with hY3 led to the upregulation of a panel of IFN transcripts, including SIGLEC1, a result corroborated using quantitative PCR. Using independent and agnostic bioinformatics approaches, CD45+CD11c+ and CD45+CD11c\u2212 human leukocytes flow sorted from the CHB hearts highly expressed type I IFN response genes inclusive of SIGLEC1. Furthermore, Siglec-1 expression was identified in the septal region of several affected fetal hearts. These data now provide a link between IFN, IFN-stimulated genes, and the inflammatory and possibly fibrosing components of CHB, positioning Siglec-1\u2013positive macrophages as integral to the process.<\/jats:p>","DOI":"10.4049\/jimmunol.1800357","type":"journal-article","created":{"date-parts":[[2018,12,5]],"date-time":"2018-12-05T22:45:14Z","timestamp":1544049914000},"page":"48-55","source":"Crossref","is-referenced-by-count":58,"title":["Siglec-1 Macrophages and the Contribution of IFN to the Development of Autoimmune Congenital Heart Block"],"prefix":"10.1093","volume":"202","author":[{"given":"Robert M","family":"Clancy","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, New York University School of Medicine , New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Halushka","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine , Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara E","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, New York University School of Medicine , New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tenzin","family":"Lhakhang","sequence":"additional","affiliation":[{"name":"Applied Bioinformatics Laboratories, New York University School of Medicine , New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, New York University School of Medicine , New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill P","family":"Buyon","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, New York University School of Medicine , New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,1,1]]},"reference":[{"key":"2025030417555781400_r1","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/j.1365-2796.2009.02100.x","article-title":"Autoimmune associated congenital heart block: integration of clinical and research clues in the management of the maternal \/ foetal dyad at risk","volume":"265","author":"Buyon","year":"2009","journal-title":"J. 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Cardiol."},{"key":"2025030417555781400_r3","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/art.11430","article-title":"Immunohistologic evidence supports apoptosis, IgG deposition, and novel macrophage\/fibroblast crosstalk in the pathologic cascade leading to congenital heart block","volume":"50","author":"Clancy","year":"2004","journal-title":"Arthritis Rheum."},{"key":"2025030417555781400_r4","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.4049\/jimmunol.169.4.2156","article-title":"Transdifferentiation of cardiac fibroblasts, a fetal factor in anti-SSA\/Ro-SSB\/La antibody-mediated congenital heart block","volume":"169","author":"Clancy","year":"2002","journal-title":"J. Immunol."},{"key":"2025030417555781400_r5","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.4049\/jimmunol.171.6.3253","article-title":"Cytokine polymorphisms and histologic expression in autopsy studies: contribution of TNF-alpha and TGF-beta 1 to the pathogenesis of autoimmune-associated congenital heart block","volume":"171","author":"Clancy","year":"2003","journal-title":"J. Immunol."},{"key":"2025030417555781400_r6","doi-asserted-by":"crossref","first-page":"30444","DOI":"10.1074\/jbc.M111.263657","article-title":"A novel role of endothelin-1 in linking Toll-like receptor 7-mediated inflammation to fibrosis in congenital heart block","volume":"286","author":"Alvarez","year":"2011","journal-title":"J. Biol. 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Immunol."},{"key":"2025030417555781400_r9","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/gene.2009.20","article-title":"Peripheral blood gene expression profiling in Sj\u00f6gren\u2019s syndrome","volume":"10","author":"Emamian","year":"2009","journal-title":"Genes Immun."},{"key":"2025030417555781400_r10","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1073\/pnas.0337679100","article-title":"Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus","volume":"100","author":"Baechler","year":"2003","journal-title":"Proc. Natl. Acad. Sci. 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Biotechnol."},{"key":"2025030417555781400_r20","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.immuni.2008.05.012","article-title":"A modular analysis framework for blood genomics studies: application to systemic lupus erythematosus","volume":"29","author":"Chaussabel","year":"2008","journal-title":"Immunity"},{"key":"2025030417555781400_r21","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1002\/art.38628","article-title":"Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures","volume":"66","author":"Chiche","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"2025030417555781400_r22","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.93009","article-title":"Single cell RNA sequencing to dissect the molecular heterogeneity in lupus nephritis","author":"Der","year":"2017","journal-title":"JCI Insight."},{"key":"2025030417555781400_r23","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1161\/ATVBAHA.117.309383","article-title":"PAI-1 (plasminogen activator inhibitor-1) expression renders alternatively activated human macrophages proteolytically quiescent","volume":"37","author":"Hohensinner","year":"2017","journal-title":"Arterioscler. 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Med."},{"key":"2025030417555781400_r26","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/0002-9343(87)90918-1","article-title":"Cardiac immunoglobulin deposition in congenital heart block associated with maternal anti-Ro autoantibodies","volume":"83","author":"Lee","year":"1987","journal-title":"Am. J. Med."},{"key":"2025030417555781400_r27","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/imr.12383","article-title":"Endosomal Toll-like receptors in clinically overt and silent autoimmunity","volume":"269","author":"Clancy","year":"2016","journal-title":"Immunol. Rev."},{"key":"2025030417555781400_r28","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/ni1576","article-title":"TNF activates an IRF1-dependent autocrine loop leading to sustained expression of chemokines and STAT1-dependent type I interferon-response genes","volume":"9","author":"Yarilina","year":"2008","journal-title":"Nat. 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