Circulating cardiac autoantibodies in dilated cardiomyopathy and myocarditis: pathogenetic and clinical significance

European Journal of Heart Failure - Tập 4 Số 4 - Trang 411-417 - 2002
Alida L.P. Caforio1, Niall Mahon2, Francesco Tona1, William J. McKenna2
1Division of Cardiology, Department of Clinical and Experimental Medicine University of Padua, Policlinico Universitario Centro ‘V. Gallucci’, via N. Giustiniani, 2 35128 Padua Italy
2Department of Cardiological Sciences, St. George's Hospital Medical School, London, UK

Tóm tắt

AbstractDilated cardiomyopathy (DCM) is a relevant cause of heart failure and a common indication for heart transplantation. It may be idiopathic, familial/genetic, viral, autoimmune or immune‐mediated associated with a viral infection. Myocarditis is an inflammatory disease of the myocardium; it may be idiopathic, infectious or autoimmune and may heal or lead to DCM. Thus, in a patient subset, myocarditis and DCM are thought to represent the acute and chronic stages of an organ‐specific autoimmune disease of the myocardium. In keeping with this hypothesis, autoimmune features in patients with myocarditis/DCM include: familial aggregation; a weak association with HLA‐DR4; abnormal expression of HLA class II on cardiac endothelium on endomyocardial biopsy; and detection of organ‐ and disease‐specific cardiac autoantibodies of the IgG class in the sera of affected patients and symptom‐free relatives. The cardiac autoantibodies detected by immunofluorescence are directed against multiple antigens. Two of these, first identified using immunoblotting and confirmed by ELISA, are the atrial‐specific α‐ and the ventricular and skeletal muscle β‐heavy chain isoform. The α‐myosin isoform fulfils the expected criteria for organ‐specific autoimmunity, in that immunization with cardiac, but not skeletal myosin reproduces, in susceptible mouse strains, the human disease phenotype of myocarditis/DCM; in addition, α‐myosin is entirely cardiac‐specific. Additional antigenic targets of heart‐reactive autoantibodies include unknown sarcolemmal proteins, mitochondrial enzymes, β‐adrenergic and muscarinic receptors. For some of these antibodies, there is in vitro evidence for a functional role. The organ‐specific cardiac autoantibodies detected by immunofluorescence in symptom‐free relatives were associated with echocardiographic features suggestive of early disease. Mid‐term follow‐up suggests that these antibodies are predictive markers of progression to DCM among symptom‐free relatives with or without abnormal echocardiographic findings.

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Tài liệu tham khảo

10.1161/01.CIR.93.5.841

10.1136/hrt.72.6_Suppl.S30

10.2165/00003495-199652040-00005

10.1016/0167-5699(93)90244-F

10.1056/NEJM199201093260201

10.1016/S0735-1097(97)00433-6

10.1016/0896-8411(90)90140-N

10.1161/01.CIR.91.3.631

10.1016/0735-1097(90)92821-I

10.1161/01.CIR.89.6.2760

10.1161/01.CIR.85.5.1734

10.1172/JCI116416

10.1016/0735-1097(93)90546-D

10.1136/hrt.74.6.598

10.1007/978-3-642-83760-9_23

10.1093/eurheartj/12.suppl_D.178

10.1093/oxfordjournals.eurheartj.a015230

10.1016/S0735-1097(10)80331-6

Maisch B., 1984, Demonstration of organ‐specific antibodies against heart mitochondria (anti‐M7) in sera from patients with some forms of heart diseases, Clin Exp Immunol, 58, 283

10.1016/S0735-1097(99)00485-4

10.1136/hrt.77.1.62

10.1016/S0735-1097(99)00172-2

10.1016/S0025-6196(12)61607-3

10.1016/S0140-6736(94)92339-6

10.1016/0002-9149(83)90535-0

Ansari A.A., 1994, Epitope mapping of the branched‐chain α‐ketoacid dehydrogenase dihydrolipoyl transacylase (BCKD‐E2) protein that reacts with sera from patients with idiopathic dilated cardiomyopathy, J Immunol, 153, 4754, 10.4049/jimmunol.153.10.4754

10.1093/eurheartj/12.suppl_D.175

10.1016/0735-1097(94)90513-4

10.1016/S1388-9842(00)00148-3

10.1046/j.1365-2249.1998.00531.x

10.1006/bbrc.1999.0761

10.1006/jmcc.1996.0253

10.1093/eurheartj/16.suppl_O.81

Maisch B., 1993, Cytolytic cross‐reactive antibodies directed against the cardiac membrane and viral proteins in Coxsackie virus B3 and B4 myocarditis. Characterization and pathogenetic relevance, Circulation, 87, V49

10.1016/S0002-9149(97)00600-0

10.1084/jem.168.6.2105

10.1016/0165-6147(94)90047-7

10.4049/jimmunol.139.11.3630

Smith S.C., 1991, Myosin‐induced myocarditis is a T‐cell‐mediated disease, J Immunol, 147, 2141, 10.4049/jimmunol.147.7.2141

10.1016/S0952-7915(99)00038-2

Caforio A.L.P., 1997, Cardiac autoantibodies may identify asymptomatic relatives at risk of dilated cardiomyopathy, J Am Coll Cardiol, 29, 193A

Caforio A.L.P., 2001, Cardiac autoantibodies are independent predictors of progression to dilated cardiomyopathy in symptom‐free relatives, Eur Heart J, 22, 637

10.1016/0896-8411(91)90185-F

10.1056/NEJM199508033330501

10.1161/01.CIR.104.1.39

10.1038/76277

10.1172/JCI7132

10.1038/76199

10.1161/01.RES.86.3.281

10.1161/01.CIR.101.4.385

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European Journal of Heart Failure

Tập 4 Số 4

411-417

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