The T-cell disorders psoriasis and celiac disease are epidemiologically
linked to atrial fibrillation (AF), a known inflammatory
and fibrotic disorder.1,2 Indirect evidence has emerged for a humoral autoimmune pathogenesis for AF.3 We believe
that AF, like psoriasis, is in fact a TH1, TH17, and TH22-related autoimmune disorder related to microRNA-ome dysregulation. MicroRNA-29 (mir29), in particular, may lead to an integrated understanding
of AF. Liston et al recently highlighted mir29’s role in regulating the polarity of the adaptive immune response.4 In the setting of mir29 deficiency, such as seen in AF, T cells are predisposed
to an activated TH1 immunophenotype. Atrial biopsies from patients with AF show frequent lymphocytic myocarditis, compatible
with this hypothesis.5 Flow cytometric findings also support a T-cell etiology, as peripheral blood from AF patients shows upregulation
of the T-cell activation markers CD69 and HLA-DR.6 Furthermore,
microRNA-29 contributes to the fibrotic arrhythmogenic substrate of atrial fibrillation (AF).7 Mir29 normally functions to inhibit
fibrosis by suppressing mRNA of extracellular matrix genes (including collagens and fibrillin). These new insights into mir29’s functions further support a role for the adaptive immune system in the immunopathogenesis of AF. We recommend that AF investigators
team up with immunologists in search for pathogenic T cells.
The authors have no relevant conflicts of interest to disclose.
- Ahlehoff O, Gislason GH, Jorgensen CH, et al. Psoriasis and risk of atrial fibrillation and ischaemic stroke: a Danish Nationwide Cohort Study. Eur Heart J 2012;33:2054-2064.
- Emilsson L, Smith JG, West J, Melander O, Ludvigsson JF. Increased risk of atrial fibrillation in patients with coeliac disease: a nationwide cohort study. Eur Heart J 2011;32:2430-2437.
- Li H, Scherlag BJ, Kem DC, et al. Atrial tachycardia provoked in the presence of activating autoantibodies to beta2-adrenergic receptor in the rabbit. Heart Rhythm 2013;10:436-441.
- Liston A, Papadopoulou AS, Danso-Abeam D, Dooley J. MicroRNA-29 in the adaptive immune system: setting the threshold. Cell Mol Life Sci 2012;69:3533-3541.
- Frustaci A, Chimenti C, Bellocci F, Morgante E, Russo MA, Maseri A. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation 1997;96:1180-1184.
- Liu L, Lee J, Fu G, et al. Activation of peripheral blood CD3(+) T-lymphocytes in patients with atrial fibrillation. Int Heart J 2012;53:221-224.
- Dawson K, Wakili R, Ordog B, et al. MicroRNA29: a mechanistic contributor and potential biomarker in atrial fibrillation. Circulation 2013;127:1466-1475, 1475e1461-1428.
Christopher S. Hale MDhalec01@nyumc.org