CCR5del32 genotype in human enteroviral cardiomyopathy leads to spontaneous virus clearance and improved outcome compared to wildtype CCR5

Autor: Heinz-Peter Schultheiss, Maria Rohde, Felicitas Escher, Dirk Lassner, Christine S. Siegismund, Uwe Kühl, Andrea Stroux
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Biopsy
T-Lymphocytes
Cardiomyopathy
lcsh:Medicine
Kaplan-Meier Estimate
030204 cardiovascular system & hematology
medicine.disease_cause
0302 clinical medicine
Genotype
Coxsackievirus
Enterovirus
medicine.diagnostic_test
biology
General Medicine
Middle Aged
Prognosis
CCR5del32 genotype
Killer Cells
Natural
Phenotype
Treatment Outcome
Cytokines
Female
Cardiomyopathies
Adult
Receptors
CCR5
Interferon-beta therapy
Antigen-Presenting Cells
Antiviral Agents
General Biochemistry
Genetics and Molecular Biology
Virus
03 medical and health sciences
Enterovirus Infections
medicine
Humans
Genotyping
Aged
Retrospective Studies
Inflammation
Polymorphism
Genetic
business.industry
Research
lcsh:R
Interferon-beta
medicine.disease
biology.organism_classification
030104 developmental biology
Heart failure
Mutation
Immunology
business
Immunologic Memory
Zdroj: Journal of Translational Medicine, Vol 16, Iss 1, Pp 1-11 (2018)
Journal of Translational Medicine
ISSN: 1479-5876
DOI: 10.1186/s12967-018-1610-8
Popis: Background Enteroviral cardiomyopathy is a life-threatening disease, and detection of enterovirus (EV) RNA in the initial endomyocardial biopsy is associated with adverse prognosis and increased mortality. Some patients with EV infection may spontaneously eliminate the virus and recover, whereas those with virus persistence deteriorate and progress to heart failure. Interferon-beta (IFN-β) therapy eliminates the virus, resulting in increased survival of treated patients. CCR5 is expressed on antigen-presenting cells (both macrophages and dendritic cells) and immune effector cells (T-lymphocytes with memory/effector phenotype and natural killer cells). Its 32-bp deletion (CCR5del32) is the most frequent human coding sequence mutation. This study addresses the correlation of CCR5 polymorphism to the clinical course of EV infection and the necessity for IFN-β treatment. Methods We examined 97 consecutive patients with chronic/inflammatory cardiomyopathy and biopsy-proven EV infection and reliable information on clinical outcomes by CCr5 genotyping. These data were evaluated in relation to virus persistence in follow-up biopsies and survival rates over a 15-year period. Results Genotyping revealed a strong correlation between the CCR5del32 genotype and spontaneous virus clearance with improved outcomes. All patients with CCR5del32 eliminated EV spontaneously and none of them died within the observed period. In the group of untreated CCR5 wildtype patients, 33% died (Kaplan–Meier log-rank p = 0.010). However, CCR5 wildtype individuals treated with IFN-β are more likely to survive than without therapy (Kaplan–Meier log-rank p = 0.004) in identical proportions to individuals with the CCR5del32 genotype. Conclusions These data suggest that CCR5 genotyping is a novel predictive genetic marker for the clinical course of human EV cardiomyopathies. Hereby clinicians can identify those EV positive individuals who will eliminate the virus spontaneously based on CCR5 phenotype and those patients with CCR5 wildtype genotype who would be eligible for immediate antiviral IFN-β treatment to minimize irreversible cardiac damage. Electronic supplementary material The online version of this article (10.1186/s12967-018-1610-8) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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