Clinical implications of anti-heart autoantibodies in myocarditis and dilated cardiomyopathy

Abstract

Dilated cardiomyopathy (DCM), a leading cause of heart failure and heart transplantation in younger adults, is characterized by dilatation and impaired contraction of the left or both ventricles; it may be idiopathic, familial/genetic (20-30%), viral, and/or immune. On endomyocardial biopsy there is chronic inflammation in 30-40% of cases. Mutations in genes encoding myocyte structural proteins, cardiotoxic noxae and infectious agents are known causes; due to high aetiologic and genetic heterogeneity, the gene defects identified so far account for a tiny proportion of the familial cases. In at least two thirds of patients, DCM remains idiopathic. Myocarditis may be idiopathic, infectious or autoimmune and may heal or lead to DCM. Circulating heart-reactive autoantibodies are found in myocarditis/DCM patients and symptom-free relatives at higher frequency than in normal or noninflammatory heart disease control groups. These autoantibodies are directed against multiple antigens, some of which are expressed only in the heart (organ-specific); some autoantibodies have functional effects on cardiac myocytes in vitro as well as in animal models. Depletion of nonantigen-specific antibodies by extracorporeal immunoadsorption is associated with improved ventricular function and reduced cardiac symptoms in some DCM patients, suggesting that autoantibodies may also have a functional role in humans. Immunosuppression seems beneficial in patients who are virus-negative and cardiac autoantibody positive. Prospective family studies have shown that cardiac-specific autoantibodies are present in at least 60% of both familial and non familial pedigrees and predict DCM development among asymptomatic relatives, years before clinical and echocardiographic evidence of disease. Animal models have shown that autoimmune myocarditis/DCM can be induced by virus as well as reproduced by immunization with a well-characterized autoantigen, cardiac myosin. Thus, in a substantial proportion of patients, myocarditis and DCM represent different stages of an organ-specific autoimmune disease, that represents the final common pathogenetic pathway of infectious and noninfectious myocardial injuries in genetically predisposed individuals.

CD69 Limits the Severity of Cardiomyopathy After Autoimmune Myocarditis

“…3,4 In addition, myocardial injury can induce an autoimmune response to heart tissue, which has an important role in the pathogenesis of myocarditis and DCM. [5][6][7] Experimental autoimmune myocarditis (EAM) is a mouse model of postinfectious myocarditis that can be induced in susceptible mouse strains by immunization with cardiac ␣-myosin heavy chain (MyHC-␣)-derived peptides or by injection of activated MyHC-␣-loaded dendritic cells. 8 -10 In this regard, it has been shown that EAM is a CD4 ϩ T-cell-mediated disease and its development depends critically on the interleukin (IL)-23-STAT4 axis, promoting the expansion of an autoreactive CD4 ϩ T-cell subset characterized by IL-17 production.…”

Improvement of Cardiac Function after Granulocyte-colony Stimulating Factor-mobilized Peripheral Blood Mononuclear Cell Implantation in a Patient with Non-ischemic Dilated Cardiomyopathy Associated with Thromboangiitis Obliterans

“…Further, most TAO patients have a history of tobacco smoking, but cardiac complications, even coronary artery disease, are a rare complication of TAO (13,14). Immunological abnormalities may involve both TAO and DCM but the precise mechanism is still unknown (18,19 (20,21). MIBG abnormalities are correlated with LVEF, New York Heart Association functional class, and histopathological abnormalities (22,23).…”

Changes in serum cardiac myosin light chain 1 levels in children with fulminant myocarditis during continuous blood purification

“…15 In patients with myocardial edema caused by various factors such as necrosis, apoptosis and cardiac myosin in the protease decomposition, high levels of CMLC-1 are released into the blood through damaged membranes. 16 As a cardiac autoantigen, CMLA-1 antigen presents cells to generate anti-cardiac myosin antibody (AMA), 17 leading to further immune damage.…”