Gene expression in giant cell myocarditis: Altered expression of immune response genes.
BACKGROUND
Giant cell myocarditis is a rapidly progressive and often fatal condition without a clear etiology or treatment. A better understanding of giant cell myocarditis pathogenesis is critical to developing treatments to prevent progression and reverse damage. We compared the gene expression of giant cell myocarditis with that of nonfailing hearts.


METHODS
Left ventricular samples from two giant cell myocarditis patients harvested during ventricular assist device placement and six unused donor hearts were examined using Affymetrix U133A microarrays. Differential gene expression was defined with a Bonferroni-adjusted p value < or = 0.05 from a Student's t-test and an absolute fold change > or = 2.0. Select gene expression was confirmed with quantitative PCR.


RESULTS
Of 115 differentially expressed genes, most were upregulated in giant cell myocarditis and involved in immune response, transcriptional regulation, and metabolism. T-cell activation genes included chemokine receptor 4; chemokine ligands 5, 9, 13, and 18; interleukin-10 receptor alpha; and beta-2 integrin.


CONCLUSIONS
Gene expression analysis of giant cell myocarditis offers novel insights into its pathogenesis, namely the role of T-cell activators of the Th1 subset and immune response genes previously implicated in heart failure. This forms the basis for future work aimed at defining novel therapeutic targets for giant cell myocarditis.
Kittleson
Michelle M
MM
Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Minhas
Khalid M
KM
Irizarry
Rafael A
RA
Ye
Shui Q
SQ
Edness
Gina
G
Breton
Elayne
E
Conte
John V
JV
Tomaselli
Gordon
G
Garcia
Joe G N
JG
Hare
Joshua M
JM
D000328:Adult; D001706:Biopsy; D016000:Cluster Analysis; D005260:Female; D015870:Gene Expression; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology; D015726:Giant Cells / Q000276:immunology / Q000473:pathology; D006352:Heart Ventricles / Q000276:immunology / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000276:immunology*
D000077278:RNA, Mitochondrial; D012313:RNA