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Enhanced expression and autoimmunity of recombination signal binding protein-jkappa in human dilated cardiomyopathy.

Abstract：

:Dilated cardiomyopathy (DCM) is a major cause of heart failure in younger individuals. Its prognosis is poor with 40-50% of patients dying within 2 years after diagnosis. Although the etiology of DCM is poorly understood, there is increasing evidence that DCM may represent an autoimmune disease in a significant subset of patients. In order to identify candidate antigens in DCM, we applied a molecular strategy which combines recombinant expression cloning and autoimmunological screening procedures. A left ventricle from a male DCM patient was explanted at heart transplantation and a human DCM left ventricular cDNA-expression library was constructed. 2 x 10(6) clones were immunologically screened with serum collected from the same patient prior transplantation. Subsequent rounds of screening and purification allowed isolation of a positive clone which was sequenced and identified as Recombination Signal Binding Protein-jkappa (RBP-jkappa). RBP-jkappa is an already identified transcription factor, e.g., involved in Epstein-Barr-virus-induced immortalization processes. Radioactively labeled RBP-jkappa protein was synthesized via in vitro translation using the isolated RBP-jkappa cDNA. This RBP-jkappa protein was used for immunoprecipitation reactions to screen sera of healthy controls and patients suffering of DCM for the presence of RBP-jkappa autoantibodies. Analysis revealed that only 31% (n = 16) of healthy but 70.6% of DCM patients (n = 17) carry an autoantibody against RBP-jkappa. Patients suffering from ischemic cardiomyopathy showed a prevalence of 22% of RBP-jkappa autoantibodies. Western analysis with an monoclonal antibody raised against RBP-jkappa showed that RBP-jkappa was overexpressed to 488 +/- 140% in DCM hearts compared to non-failing controls (n = 8). Autologous immunological screening of a cDNA expression library is a powerful and novel technology to gain insights into the etiology of human idiopathic DCM. Human DCM displays an autoimmune response against RBP-jkappa and an overexpression of RBP-jkappa. Since RBP-jkappa is involved in cellular immortalization and exerts antiapoptotic effects, the increased RBP-jkappa autoantibody level during DCM may inhibit this growth-regulating feature of RBP-jkappa. In this setting, enhanced myocardial RBP-jkappa expression could represent a compensatory but ineffective response to counteract the increased rate of apoptosis in DCM. Furthermore, RBP-jkappa may be a useful diagnostic marker for DCM.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Nickenig G,Wolff M,Stäblein A,Pfister H,Böhm M

doi

10.1006/bbrc.1999.1855

subject

Has Abstract

pub_date

1999-12-20 00:00:00

pages

432-6

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(99)91855-7

journal_volume

266

pub_type

杂志文章

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Enhanced expression and autoimmunity of recombination signal binding protein-jkappa in human dilated cardiomyopathy.