Immunoadsorption and subsequent immunoglobulin substitution decreases myocardial gene expression of desmin in dilated cardiomyopathy.
Cardiac autoantibodies play a pathogenic role in dilated cardiomyopathy (DCM). Removal of antibodies by immunoadsorption (IA) induces hemodynamic improvement in DCM patients. The present study investigated the effects of IA on myocardial gene expression of the intermediate cytoskeletal filament desmin, which is upregulated in heart failure. RNA was isolated from five explanted non-failing hearts and five explanted failing hearts of DCM patients, and myocardial gene expression of desmin was estimated by real-time polymerase chain reaction (PCR). In a case-control study in six DCM patients (LVEF < 40%, NYHA II-III), IA and subsequent IgG substitution were performed at monthly intervals until month 3. Endomyocardial biopsies (EMBs) were obtained before and after IA (after 3-6 months). From six DCM patients without IA therapy (controls), EMBs were also obtained over a comparable time interval. Expression of the desmin gene was analyzed in these EMBs by real-time PCR. In failing explanted hearts, expression of desmin was significantly increased (0.88 +/- 0.12 vs 0.45 +/- 0.15 in non-failing hearts, P < 0.05). After IA, myocardial gene expression of desmin was significantly decreased (from 0.26 +/- 0.05 [baseline] to 0.14 +/- 0.04 [P < 0.05] vs baseline and controls). Removal of antibodies by IA modulates myocardial gene expression of desmin in DCM patients.
Kallwellis-Opara
Angela
A
Department of Internal Medicine B, University of Greifswald, Greifswald, Germany.
Staudt
Alexander
A
Trimpert
Christiane
C
Noutsias
Michel
M
Kühl
Uwe
U
Pauschinger
Matthias
M
Schultheiss
Heinz-Peter
HP
Grube
Markus
M
Böhm
Michael
M
Baumann
Gert
G
Völker
Uwe
U
Kroemer
Heyo K
HK
Felix
Stephan B
SB
D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D016022:Case-Control Studies; D003893:Desmin / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007163:Immunosorbent Techniques; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010865:Pilot Projects; D012333:RNA, Messenger / Q000378:metabolism; D012107:Research Design; D013997:Time Factors; D046509:Tissue Culture Techniques
D001323:Autoantibodies; D003893:Desmin; D016756:Immunoglobulins, Intravenous; D012333:RNA, Messenger