Many factors contribute to the pathogenesis of atrial fibrillation, including electrical, structural, neurohumoral, and inflammatory mechanisms. 1 Schotten U. Verheule S. Kirchhof P. Goette A. Pathophysiological mechanisms of atrial fibrillation: a translational appraisal. Physiol Rev. 2011; 91: 265-325 Crossref PubMed Scopus (854) Google Scholar Our review indicated that various autoantibodies that may play a role in the development and maintenance of atrial fibrillation have been identified. 2 Lee H.C. Huang K.T. Wang X.L. Shen W.K. Autoantibodies and cardiac arrhythmias. Heart Rhythm. 2011; 8: 1788-1795 Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Indeed, mounting evidence demonstrates correlations between diseases with autoimmune mechanisms, including Graves' disease, 3 Stavrakis S. Yu X. Patterson E. et al. Activating autoantibodies to the beta-1 adrenergic and m2 muscarinic receptors facilitate atrial fibrillation in patients with Graves' hyperthyroidism. J Am Coll Cardiol. 2009; 54: 1309-1316 Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar celiac disease, 4 Emilsson L. Smith J.G. West J. Melander O. Ludvigsson J.F. Increased risk of atrial fibrillation in patients with coeliac disease: a nationwide cohort study. Eur Heart J. 2011; 32: 2430-2437 Crossref PubMed Scopus (69) Google Scholar and psoriasis, 5 Ahlehoff O. Gislason G.H. Jorgensen C.H. et al. Psoriasis and risk of atrial fibrillation and ischaemic stroke: a Danish nationwide cohort study. Eur Heart J. 2011; (Epub ahead of print) PubMed Google Scholar and an increased risk of atrial fibrillation. Schairer and Levis suggested that T-cell–mediated autoimmune disorders should be considered in the pathogenesis of atrial fibrillation. Such mechanisms in atrial fibrillation are currently unknown and unexplored. They proposed the intriguing hypothesis that atrial fibrillation is a T-cell autoimmune disorder involving cytotoxic T helper cells acting on His-Purkinje cells, which express contactin-2, a target of TH17 in patients with multiple sclerosis. 6 Derfuss T. Parikh K. Velhin S. et al. Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals. Proc Natl Acad Sci USA. 2009; 106: 8302-8307 Crossref PubMed Scopus (172) Google Scholar It is not known whether patients with multiple sclerosis have a higher incidence of atrial fibrillation, but paroxysmal atrial fibrillation associated with attacks of multiple sclerosis has been reported. 7 Chagnac Y. Martinovits G. Tadmor R. Goldhammer Y. Paroxysmal atrial fibrillation associated with an attack of multiple sclerosis. Postgrad Med J. 1986; 62: 385-387 Crossref PubMed Scopus (24) Google Scholar , 8 Schroth W.S. Tenner S.M. Rappaport B.A. Mani R. Multiple sclerosis as a cause of atrial fibrillation and electrocardiographic changes. Arch Neurol. 1992; 49: 422-424 Crossref PubMed Scopus (37) Google Scholar Most of the His-Purkinje cells are in the ventricles, and Purkinje fibers are implicated in the development of idiopathic ventricular fibrillation. 9 Haissaguerre M. Shoda M. Jais P. et al. Mapping and ablation of idiopathic ventricular fibrillation. Circulation. 2002; 106: 962-967 Crossref PubMed Scopus (550) Google Scholar It is thought-provoking that atrial Purkinje cells may similarly precipitate fibrillation in the atria. The recently reported association as well as potential immune-mediated mechanisms leading to atrial fibrillation in psoriasis needs to be validated and further explored. Although TH1–TH17 cells are critical to induce the skin pathology of psoriasis, the potential for disease-linked autoantibody, cytokine, or other autoinflammatory-mediated mechanisms will need to be examined in the subpopulation of patients with psoriasis who develop or are at risk for atrial fibrillation. Proteomic, immune, and molecular screening technologies to identify and characterize these pathogenic mechanisms can be leveraged to enhance the yield in this search. Adoptive transfer studies reported by Derfuss et al 6 Derfuss T. Parikh K. Velhin S. et al. Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals. Proc Natl Acad Sci USA. 2009; 106: 8302-8307 Crossref PubMed Scopus (172) Google Scholar may be useful but have limitations to more broadly characterize novel disease pathomechanisms. We fully agree that further studies to investigate atrial fibrillation in autoimmune disorders as well as to delineate autoimmune mechanisms in idiopathic atrial fibrillation are warranted. Connexin43 and the regulation of intercalated disc functionHeart RhythmVol. 9Issue 5PreviewGap junctions mediate the passage of ions and small molecules between cells. In the adult working cardiac ventricles, gap junctions are formed predominantly by the oligomerization of the 43-kDa protein Connexin43 (Cx43). It is generally accepted that gap junction–mediated intercellular communication is modulated by changes in the intracellular environment. The activity of various kinases, the concentration of protons or calcium, and the association of Cx43 with other intracellular components all converge to determine the filtering capabilities of intercellular channels. Full-Text PDF