Humoral anti-proteasomal autoimmunity in dilated cardiomyopathy

被引：14

作者：

Voigt, Antje ^{[2
]}

Bartel, Katrin ^{[2
]}

Egerer, Karl ^{[4
]}

Trimpert, Christiane ^{[3
]}

Feist, Eugen ^{[4
]}

Gericke, Christine ^{[5
]}

Kandolf, Reinhard ^{[6
]}

Klingel, Karin ^{[6
]}

Kuckelkorn, Ulrike ^{[1
]}

Stangl, Karl ^{[2
]}

Felix, Stephan B. ^{[3
]}

Baumann, Gert ^{[2
]}

Kloetzel, Peter-M. ^{[1
]}

Staudt, Alexander ^{[3
]}

机构：

[1] Charite, Inst Biochem CC2, D-10117 Berlin, Germany

[2] Charite, Med Klin Kardiol & Angiol, D-10117 Berlin, Germany

[3] Ernst Moritz Arndt Univ Greifswald, Klin Innere Med B, Greifswald, Germany

[4] Charite, Med Klin Rheumatol & Immunol, D-10117 Berlin, Germany

[5] Charite, Inst Med Biometrie, D-10117 Berlin, Germany

[6] Univ Tubingen, D-72076 Tubingen, Germany

来源：

BASIC RESEARCH IN CARDIOLOGY | 2010年 / 105卷 / 01期

关键词：

Viral heart disease; Proteasome; Cardiomyopathy; Autoimmunity; MACROMOLECULAR PROTEIN COMPONENT; SYSTEMIC-LUPUS-ERYTHEMATOSUS; LEFT-VENTRICULAR DYSFUNCTION; CHRONIC HEART-FAILURE; CARDIAC DYSFUNCTION; MYOCARDIAL IMMUNOPROTEASOMES; BETA(1)-ADRENERGIC RECEPTOR; MULTICATALYTIC PROTEINASE; NATRIURETIC PEPTIDE; POTENTIAL ROLE;

D O I：

10.1007/s00395-009-0061-z

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Virus-induced chronic inflammation, autoimmune processes and impaired protein quality control may be involved in the pathogenesis of dilated cardiomyopathy (DCM). The ubiquitin-proteasome system is important in the modulation of inflammatory processes and the immune response. Proteasomes were identified as targets of a humoral autoimmune response in systemic inflammatory diseases, which provoked us to investigate anti-proteasomal immunity in DCM in detail: a total of 90 DCM patients with impaired left-ventricular function (LVEF a parts per thousand currency sign 45%) were enrolled in this study. Autoimmune response to cardiac proteasomes was found to be enhanced in DCM patients, revealing the detection of predominantly alpha subunits of the 20S proteasome complex. Proteasome antibody (ProtAb) levels were found to be particularly enhanced at stages of advanced heart failure: moderately decreased LVEF and considerably increased NT-pro BNP levels were observed in DCM patients who tested positive for ProtAb (P < 0.05). A linear regression model suggested a link between the detection of cardiotropic viruses in endomyocardial biopsies and anti-proteasomal immunity (P < 0.01). Likewise, ProtAb levels were enhanced in a murine model of chronic enterovirus myocarditis. Our data also point to a potential interaction of ProtAb with the cell surface: ProtAb exerted negative inotropic effects in field-stimulated cardiomyocytes. In conclusion, humoral autoreactive anti-proteasome immune responses appear to be enhanced in DCM. Viral infection of the myocardium may be linked to the induction of anti-proteasomal immunity in DCM.

引用

页码：9 / 18

页数：10

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