title: Myocardial gene expression profiles and cardiodepressant autoantibodies predict response of patients with dilated cardiomyopathy to immunoadsorption therapy.
abstract: OBJECTIVE
  Immunoadsorption with subsequent immunoglobulin G substitution (IA/IgG) represents a novel therapeutic approach in the treatment of dilated cardiomyopathy (DCM) which leads to the improvement of left ventricular ejection fraction (LVEF). However, response to this therapeutic intervention shows wide inter-individual variability. In this pilot study, we tested the value of clinical, biochemical, and molecular parameters for the prediction of the response of patients with DCM to IA/IgG.
  
  
  RESULTS
  Forty DCM patients underwent endomyocardial biopsies (EMBs) before IA/IgG. In eight patients with normal LVEF (controls), EMBs were obtained for clinical reasons. Clinical parameters, negative inotropic activity (NIA) of antibodies on isolated rat cardiomyocytes, and gene expression profiles of EMBs were analysed. Dilated cardiomyopathy patients displaying improvement of LVEF (≥20 relative and ≥5% absolute) 6 months after IA/IgG were considered responders. Compared with non-responders (n = 16), responders (n = 24) displayed shorter disease duration (P = 0.006), smaller LV internal diameter in diastole (P = 0.019), and stronger NIA of antibodies. Antibodies obtained from controls were devoid of NIA. Myocardial gene expression patterns were different in responders and non-responders for genes of oxidative phosphorylation, mitochondrial dysfunction, hypertrophy, and ubiquitin-proteasome pathway. The integration of scores of NIA and expression levels of four genes allowed robust discrimination of responders from non-responders at baseline (BL) [sensitivity of 100% (95% CI 85.8-100%); specificity up to 100% (95% CI 79.4-100%); cut-off value: -0.28] and was superior to scores derived from antibodies, gene expression, or clinical parameters only.
  
  
  CONCLUSIONS
  Combined assessment of NIA of antibodies and gene expression patterns of DCM patients at BL predicts response to IA/IgG therapy and may enable appropriate selection of patients who benefit from this therapeutic intervention.
authors.affiliation: Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Universitätsmedizin Greifswald, Friedrich-Ludwig-Jahn-Strasse 15a, Greifswald D - 17487, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Ameling
authors.forename: Lars R
authors.initials: LR
authors.lastname: Herda
authors.forename: Elke
authors.initials: E
authors.lastname: Hammer
authors.forename: Leif
authors.initials: L
authors.lastname: Steil
authors.forename: Alexander
authors.initials: A
authors.lastname: Teumer
authors.forename: Christiane
authors.initials: C
authors.lastname: Trimpert
authors.forename: Marcus
authors.initials: M
authors.lastname: Dörr
authors.forename: Heyo K
authors.initials: HK
authors.lastname: Kroemer
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kandolf
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
authors.forename: Stephan B
authors.initials: SB
authors.lastname: Felix
mesh_terms: D001323:Autoantibodies / Q000378:metabolism*; D001706:Biopsy; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression / Q000235:genetics / Q000276:immunology*; D006439:Hemodynamics / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007163:Immunosorbent Techniques; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010865:Pilot Projects; D013318:Stroke Volume / Q000235:genetics / Q000276:immunology; D059467:Transcriptome; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000276:immunology / Q000628:therapy
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G