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Induction of autoimmune response to the extracellular loop of the HERG channel pore induces QTc prolongation in guinea-pigs

Induction of autoimmune response to the extracellular loop of the HERG channel pore induces QTc prolongation in guinea-pigs

Authors :
Fabris, Frank
Yue, Yuankun
Yongxia, Qu
Chahine, Mohamed
Sobie, Eric
Lee, Peng
Wieczorek, Rosemary
Jiang, Xian Cheng
Capecchi, PIER LEOPOLDO
LAGHI PASINI, Franco
Lazzerini, PIETRO ENEA
Boutjdir, Mohamed
Source :
The Journal of physiology. 594(21)
Publication Year :
2016

Abstract

Channelopathies of autoimmune origin are novel and are associated with corrected QT (QTc) prolongation and complex ventricular arrhythmias.We have recently demonstrated that anti‐SSA/Ro antibodies from patients with autoimmune diseases and with QTc prolongation on the ECG target the human ether‐à‐go‐go‐related gene (HERG) K+ channel by inhibiting the corresponding current, I Kr, at the pore region.Immunization of guinea‐pigs with a peptide (E‐pore peptide) corresponding to the extracellular loop region connecting the S5 and S6 segments of the HERG channel induces high titres of antibodies that inhibit I Kr, lengthen the action potential and cause QTc prolongation on the surface ECG. In addition, anti‐SSA/Ro‐positive sera from patients with connective tissue diseases showed high reactivity to the E‐pore peptide.The translational impact is the development of a peptide‐based approach for the diagnosis and treatment of autoimmune‐associated long QT syndrome.

Details

ISSN :
14697793
Volume :
594
Issue :
21
Database :
OpenAIRE
Journal :
The Journal of physiology
Accession number :
edsair.pmid.dedup....ba1e3b86750b21bbf5f087e8b6903cda