title: Improved diagnosis of idiopathic giant cell myocarditis and cardiac sarcoidosis by myocardial gene expression profiling.
abstract: OBJECTIVE
  Improvement of clinical diagnostics of idiopathic giant cell myocarditis (IGCM) and cardiac sarcoidosis (CS), two frequently fatal human myocardial diseases. Currently, IGCM and CS are diagnosed based on differential patterns of inflammatory cell infiltration and non-caseating granulomas in histological sections of endomyocardial biopsies (EMBs), after heart explantation or postmortem. We report on a method for improved differential diagnosis by myocardial gene expression profiling in EMBs.
  
  
  RESULTS
  We examined gene expression profiles in EMBs from 10 patients with histopathologically proven IGCM, 10 with CS, 18 with active myocarditis (MCA), and 80 inflammation-free control subjects by quantitative RT-QPCR. We identified distinct differential profiles that allowed a clear discrimination of tissues harbouring giant cells (IGCS, CS) from those with MCA or inflammation-free controls. The expression levels of genes coding for cytokines or chemokines (CCL20, IFNB1, IL6, IL17D; P < 0.05), cellular receptors (ADIPOR2, CCR5, CCR6, TLR4, TLR8; P < 0.05), and proteins involved in the mitochondrial energy metabolism (CPT1, CYB, DHODH; P < 0.05) were deregulated in 2- to 300-fold, respectively. Bioinformatic analyses and correlation of the gene expression data with immunohistochemical findings provided novel information regarding the differential cellular and molecular pathomechanisms in IGCM, CS, and MCA.
  
  
  CONCLUSIONS
  Myocardial gene expression profiling is a reliable method to predict the presence of multinuclear giant cells in the myocardium, even without a direct histological proof, in single small EMB sections, and thus to reduce the risk of sampling errors. This profiling also facilitates the discrimination between IGCM and CS, as two different clinical entities that require immediate and tailored differential therapy.
authors.affiliation: Institute of Cardiac Diagnostics and Therapy, Moltkestrasse 31, D-12203 Berlin, Germany info@ikdt.de.
authors.forename: D
authors.initials: D
authors.lastname: Lassner
authors.affiliation: Institute of Cardiac Diagnostics and Therapy, Moltkestrasse 31, D-12203 Berlin, Germany Department of Cardiology and Pneumonology, Charité - University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Kühl
authors.affiliation: Institute of Cardiac Diagnostics and Therapy, Moltkestrasse 31, D-12203 Berlin, Germany.
authors.forename: C S
authors.initials: CS
authors.lastname: Siegismund
authors.affiliation: Institute of Cardiac Diagnostics and Therapy, Moltkestrasse 31, D-12203 Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Rohde
authors.affiliation: Institute of Pathology, Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Elezkurtaj
authors.affiliation: Institute of Cardiac Diagnostics and Therapy, Moltkestrasse 31, D-12203 Berlin, Germany Department of Cardiology and Pneumonology, Charité - University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Escher
authors.affiliation: Department of Cardiology and Pneumonology, Charité - University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Tschöpe
authors.affiliation: Institute of Cardiac Diagnostics and Therapy, Moltkestrasse 31, D-12203 Berlin, Germany.
authors.forename: U M
authors.initials: UM
authors.lastname: Gross
authors.affiliation: Department of Cardiology and Pneumonology, Charité - University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Poller
authors.affiliation: Department of Cardiology and Pneumonology, Charité - University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: H-P
authors.initials: HP
authors.lastname: Schultheiss
mesh_terms: D009202:Cardiomyopathies / Q000175:diagnosis*; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000175:diagnosis; D012189:Retrospective Studies; D012507:Sarcoidosis / Q000175:diagnosis*
chemical_list: D018076:DNA, Complementary
keywords: CCL20; CCR6; Cardiac sarcoidosis; Dendritic cells; Gene profiling; Idiopathic giant cell myocarditis