{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:11:07Z","timestamp":1792030267258,"version":"4.4.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2015,7,28]]},"abstract":"<jats:sec><jats:title>Background\u2014<\/jats:title><jats:p>Emerging clinical evidence demonstrates high prevalence of QTc prolongation and complex ventricular arrhythmias in patients with anti-Ro antibody (anti-Ro Ab)\u2013positive autoimmune diseases. We tested the hypothesis that anti-Ro Abs target the HERG (human ether-a-go-go\u2013related gene) K<jats:sup>+<\/jats:sup>channel, which conducts the rapidly activating delayed K<jats:sup>+<\/jats:sup>current,<jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub>, thereby causing delayed repolarization seen as QT interval prolongation on the ECG.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results\u2014<\/jats:title><jats:p>Anti-Ro Ab\u2013positive sera, purified IgG, and affinity-purified anti-52kDa Ro Abs from patients with autoimmune diseases and QTc prolongation were tested on<jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub>using HEK293 cells expressing HERG channel and native cardiac myocytes. Electrophysiological and biochemical data demonstrate that anti-Ro Abs inhibit<jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub>to prolong action potential duration by directly binding to the HERG channel protein. The 52-kDa Ro antigen\u2013immunized guinea pigs showed QTc prolongation on ECG after developing high titers of anti-Ro Abs, which inhibited native<jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub>and cross-reacted with guinea pig ERG channel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions\u2014<\/jats:title><jats:p>The data establish that anti-Ro Abs from patients with autoimmune diseases inhibit<jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub>by cross-reacting with the HERG channel likely at the pore region where homology between anti\u201352-kDa Ro antigen and HERG channel is present. The animal model of autoimmune-associated QTc prolongation is the first to provide strong evidence for a pathogenic role of anti-Ro Abs in the development of QTc prolongation. It is proposed that adult patients with anti-Ro Abs may benefit from routine ECG screening and that those with QTc prolongation should receive counseling about drugs that may increase the risk for life-threatening arrhythmias.<\/jats:p><\/jats:sec>","DOI":"10.1161\/circulationaha.115.009800","type":"journal-article","created":{"date-parts":[[2015,5,21]],"date-time":"2015-05-21T01:32:24Z","timestamp":1432171944000},"page":"230-240","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":79,"title":["Pathogenesis of the Novel Autoimmune-Associated Long-QT Syndrome"],"prefix":"10.1161","volume":"132","author":[{"given":"Yuankun","family":"Yue","sequence":"first","affiliation":[{"name":"From Cardiovascular Research Program, VA New York Harbor Healthcare System, Brooklyn (Y.Y., U.S., F.F., K.S., Z.L., Y.Q., N.E.-S., M.M.H., X.-C.J., M.B.); Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Italy (M.C., P.-L.C., F.L.-P., P.-E.L.); Departments of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn (U.S., F.F., Z.L., Y.Q., M.M.H., X.-C.J., M.B.); Knight Cardiovascular Institute, Oregon Health &amp;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Castrichini","sequence":"additional","affiliation":[{"name":"From Cardiovascular Research Program, VA New York Harbor Healthcare System, Brooklyn (Y.Y., U.S., F.F., K.S., Z.L., Y.Q., N.E.-S., M.M.H., X.-C.J., M.B.); Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Italy (M.C., P.-L.C., F.L.-P., P.-E.L.); Departments of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn (U.S., F.F., Z.L., Y.Q., M.M.H., X.-C.J., M.B.); Knight Cardiovascular Institute, Oregon Health &amp;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ujala","family":"Srivastava","sequence":"additional","affiliation":[{"name":"From Cardiovascular Research Program, VA New York Harbor Healthcare System, Brooklyn (Y.Y., U.S., F.F., K.S., Z.L., Y.Q., N.E.-S., M.M.H., X.-C.J., M.B.); Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Italy (M.C., P.-L.C., F.L.-P., P.-E.L.); Departments of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn (U.S., F.F., Z.L., Y.Q., M.M.H., X.-C.J., M.B.); Knight Cardiovascular Institute, Oregon Health &amp;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Fabris","sequence":"additional","affiliation":[{"name":"From Cardiovascular Research Program, VA New York Harbor Healthcare System, Brooklyn (Y.Y., U.S., F.F., K.S., Z.L., Y.Q., N.E.-S., M.M.H., X.-C.J., M.B.); Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Italy (M.C., P.-L.C., F.L.-P., P.-E.L.); Departments of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn (U.S., F.F., Z.L., Y.Q., M.M.H., X.-C.J., M.B.); Knight Cardiovascular Institute, Oregon Health &amp;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krupa","family":"Shah","sequence":"additional","affiliation":[{"name":"From Cardiovascular Research Program, VA New York Harbor Healthcare System, Brooklyn (Y.Y., U.S., F.F., K.S., Z.L., Y.Q., N.E.-S., M.M.H., X.-C.J., M.B.); Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Italy (M.C., P.-L.C., F.L.-P., P.-E.L.); Departments of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn (U.S., F.F., Z.L., Y.Q., M.M.H., X.-C.J., M.B.); Knight Cardiovascular Institute, Oregon Health &amp;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Li","sequence":"additional","affiliation":[{"name":"From Cardiovascular Research Program, VA New York Harbor Healthcare System, Brooklyn (Y.Y., U.S., F.F., K.S., Z.L., Y.Q., N.E.-S., M.M.H., X.-C.J., M.B.); Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Italy (M.C., P.-L.C., F.L.-P., P.-E.L.); Departments of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn (U.S., F.F., Z.L., Y.Q., M.M.H., X.-C.J., M.B.); Knight Cardiovascular Institute, Oregon Health &amp;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxia","family":"Qu","sequence":"additional","affiliation":[{"name":"From Cardiovascular Research Program, VA New York Harbor Healthcare System, Brooklyn (Y.Y., U.S., F.F., K.S., Z.L., Y.Q., N.E.-S., M.M.H., X.-C.J., M.B.); Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Italy (M.C., P.-L.C., F.L.-P., P.-E.L.); Departments of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn (U.S., F.F., Z.L., Y.Q., M.M.H., X.-C.J., M.B.); Knight Cardiovascular Institute, Oregon Health &amp;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil","family":"El-Sherif","sequence":"additional","affiliation":[{"name":"From Cardiovascular Research Program, VA New York Harbor Healthcare System, Brooklyn (Y.Y., U.S., F.F., K.S., Z.L., Y.Q., N.E.-S., M.M.H., X.-C.J., M.B.); Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Italy (M.C., P.-L.C., F.L.-P., P.-E.L.); Departments of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn (U.S., F.F., Z.L., Y.Q., M.M.H., X.-C.J., M.B.); Knight Cardiovascular Institute, Oregon Health &amp;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengfeng","family":"Zhou","sequence":"additional","affiliation":[{"name":"From Cardiovascular Research Program, VA New York Harbor Healthcare System, Brooklyn (Y.Y., U.S., F.F., K.S., Z.L., Y.Q., N.E.-S., M.M.H., X.-C.J., M.B.); 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