CCR5del32 genotype in human enteroviral cardiomyopathy leads to spontaneous virus clearance and improved outcome compared to wildtype CCR5
Abstract 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, wh...
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| Format: | Article |
| Language: | English |
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BMC
2018-09-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-018-1610-8 |
| _version_ | 1811277415918338048 |
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| author | Dirk Lassner Christine S. Siegismund Uwe Kühl Maria Rohde Andrea Stroux Felicitas Escher Heinz-Peter Schultheiss |
| author_facet | Dirk Lassner Christine S. Siegismund Uwe Kühl Maria Rohde Andrea Stroux Felicitas Escher Heinz-Peter Schultheiss |
| author_sort | Dirk Lassner |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T00:16:20Z |
| format | Article |
| id | doaj.art-f1e65e54b3a14ca9952d2d2fa549bfde |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-13T00:16:20Z |
| publishDate | 2018-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-f1e65e54b3a14ca9952d2d2fa549bfde2022-12-22T03:10:56ZengBMCJournal of Translational Medicine1479-58762018-09-0116111110.1186/s12967-018-1610-8CCR5del32 genotype in human enteroviral cardiomyopathy leads to spontaneous virus clearance and improved outcome compared to wildtype CCR5Dirk Lassner0Christine S. Siegismund1Uwe Kühl2Maria Rohde3Andrea Stroux4Felicitas Escher5Heinz-Peter Schultheiss6Institute of Cardiac Diagnostics and Therapy (IKDT)Institute of Cardiac Diagnostics and Therapy (IKDT)Institute of Cardiac Diagnostics and Therapy (IKDT)Institute of Cardiac Diagnostics and Therapy (IKDT)Institute of Biometry and Clinical Epidemiology, Campus Benjamin Franklin, Charité-University Hospital and Berlin Institute of HealthInstitute of Cardiac Diagnostics and Therapy (IKDT)Institute of Cardiac Diagnostics and Therapy (IKDT)Abstract 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.http://link.springer.com/article/10.1186/s12967-018-1610-8CardiomyopathyCCR5del32 genotypeCoxsackievirusEnterovirusInterferon-beta therapy |
| spellingShingle | Dirk Lassner Christine S. Siegismund Uwe Kühl Maria Rohde Andrea Stroux Felicitas Escher Heinz-Peter Schultheiss CCR5del32 genotype in human enteroviral cardiomyopathy leads to spontaneous virus clearance and improved outcome compared to wildtype CCR5 Journal of Translational Medicine Cardiomyopathy CCR5del32 genotype Coxsackievirus Enterovirus Interferon-beta therapy |
| title | CCR5del32 genotype in human enteroviral cardiomyopathy leads to spontaneous virus clearance and improved outcome compared to wildtype CCR5 |
| title_full | CCR5del32 genotype in human enteroviral cardiomyopathy leads to spontaneous virus clearance and improved outcome compared to wildtype CCR5 |
| title_fullStr | CCR5del32 genotype in human enteroviral cardiomyopathy leads to spontaneous virus clearance and improved outcome compared to wildtype CCR5 |
| title_full_unstemmed | CCR5del32 genotype in human enteroviral cardiomyopathy leads to spontaneous virus clearance and improved outcome compared to wildtype CCR5 |
| title_short | CCR5del32 genotype in human enteroviral cardiomyopathy leads to spontaneous virus clearance and improved outcome compared to wildtype CCR5 |
| title_sort | ccr5del32 genotype in human enteroviral cardiomyopathy leads to spontaneous virus clearance and improved outcome compared to wildtype ccr5 |
| topic | Cardiomyopathy CCR5del32 genotype Coxsackievirus Enterovirus Interferon-beta therapy |
| url | http://link.springer.com/article/10.1186/s12967-018-1610-8 |
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