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Genotypic and serotypic profile in dilated cardiomyopathy
L Wesslén1, A Waldenström, B Lindblom
1Department of Infectious Diseases, University Hospital, Uppsala, Sweden.
Insights
Dilated cardiomyopathy (DCM) may be linked to Coxsackie B virus infections and specific human leukocyte antigen (HLA) genotypes. This study suggests a dual dependence of host genotype and virus serotype in DCM pathogenesis.
Area of Science:
- Cardiology
- Virology
- Immunogenetics
Background:
- Dilated cardiomyopathy (DCM) is a complex heart condition with unclear etiology.
- Viral infections, particularly Coxsackie B viruses, are suspected contributors to DCM.
- Genetic predisposition may play a role in DCM development.
Purpose of the Study:
- To investigate the potential role of Coxsackie B virus serology and human leukocyte antigen (HLA) genotypes in the pathogenesis of DCM.
- To explore the relationship between viral infections, host genetics, and DCM development.
Main Methods:
- Enrolled 18 patients diagnosed with DCM.
- Conducted conventional clinical investigations, including imaging and biopsy.
- Performed serological tests for Coxsackie B viruses and DNA-based tissue typing for HLA genotypes (DQB1).
Main Results:
- High IgM titers against Coxsackie viruses were found in 6/8 patients with idiopathic DCM.
- A significant association was observed between DCM and the HLA-DQB1:4 genotype (6/12 patients vs. 17% controls).
- The HLA-DQB1:2 genotype showed a protective effect, occurring in only 1/12 DCM patients versus 19% in controls.
Conclusions:
- The findings support a dual dependence of host genotype and virus serotype in DCM pathogenesis, aligning with the Doherty-Zinkernagel hypothesis.
- Suggests a virus-immune hypothesis for the enigmatic pathogenesis of DCM.
- Highlights the potential protective role of the HLA-DQB1:2 genotype in DCM.
Abstract:
Eighteen consecutive patients, admitted with a diagnosis of dilated cardiomyopathy (DCM), to the Cardiology Section, Department of Internal Medicine, University Hospital, Uppsala, Sweden were enrolled into the study. All patients suffered signs of cardiac incompensation of variable duration. Patients were defined by conventional clinical investigations including chest X-ray, ultrasound, g-camera, catheterization and endomyocardial biopsy with histological evaluation by a specially trained pathologist. Angiography was performed to exclude ischemic heart disease. Several patients were diagnosed as having a specific reason for the cardiac insufficiency, like pheochromocytoma, SLE, ethylism, ischemic heart disease and hypertrophic cardiomyopathy. In this group all 7/7 had negative serology against Coxsackie B viruses. In the other group of idiopathic CM, no other etiology could be found. Serological analysis in this group showed high IgM titres against Coxsackie viruses in 6/8 patients. EDTA-blood was taken for tissue-typing using DNA probe hybridisation. 6/12 patients had DQB1:4 using the newest nomenclature, vs 17% in the control population. The reversed picture was observed for DQB1:2, occurring in 1/12 patients, vs 19% in the normal population, thus indicating a protective value of this genotype, which to our knowledge has not been described before. The results indicate a dual dependence of (host) genotype and (virus) serotype according to the Doherty-Zinkernagel hypothesis. Thus, it would also be in agreement with the virus-immune hypothesis suggested more than 20 years ago to explain the enigmatic pathogenesis of DCM.