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An Improved and High Throughput Respiratory Syncytial Virus RSV Micro-neutralization Assay
Published on: January 26, 2019
Infant RSV immunoprophylaxis changes nasal epithelial DNA methylation at 6 years of age
Cheng-Jian Xu1,2,3,4, Nienke M Scheltema5, Cancan Qi6,7
1Centre for Individualised Infection Medicine, CiiM, a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
Insights
Infant respiratory syncytial virus (RSV) immunoprophylaxis impacts long-term nasal cell epigenetic patterns, affecting sensory perception and immune responses by age 6.
Area of Science:
- Immunology
- Epigenetics
- Pediatrics
Background:
- Respiratory syncytial virus (RSV) infection is linked to childhood wheeze and asthma.
- Persistent epigenetic alterations are a potential mechanism for these long-term effects.
Purpose of the Study:
- To investigate the long-term epigenetic effects of RSV immunoprophylaxis in infancy.
- To determine if RSV immunoprophylaxis influences asthma development through epigenetic changes.
Main Methods:
- The MAKI trial randomized 429 preterm infants to receive RSV immunoprophylaxis (palivizumab) or placebo.
- Children were followed until age 6 for asthma evaluation.
- DNA methylation in nasal cells at age 6 was analyzed using the Illumina MethylationEPIC array.
Main Results:
- RSV immunoprophylaxis significantly altered global methylation patterns in nasal cells at age 6.
- Key pathways affected included sensory perception of smell and T cell differentiation.
- Differential methylation was observed at specific CpG sites (cg18040241, cg08243963, cg19555973) but not directly associated with asthma.
Conclusions:
- RSV immunoprophylaxis in infancy has lasting effects on nasal epigenetic signatures.
- These epigenetic changes relate to host sensory perception and adaptive immune responses.
- This study offers the first evidence of long-term epigenetic impacts of RSV immunoprophylaxis.
Background:
Respiratory syncytial virus (RSV) infection has been associated with childhood wheeze and asthma, and potential mechanisms include persistent epigenetic effects.
Methods:
In the randomized, placebo-controlled MAKI trial, 429 preterm infants randomly received RSV immunoprophylaxis with palivizumab or placebo during their first RSV season. Children were followed until age 6 for asthma evaluation. DNA methylation in cells obtained by nasal brushes at age 6 was measured by Illumina MethylationEPIC array.
Results:
RSV immunoprophylaxis in infancy had a significant impact on global methylation patterns in nasal cells at age 6. The first principal component (PC) related to the immunoprophylaxis intervention was enriched for the pathway "detection of chemical stimulus involved in sensory perception of smell" and "T cell differentiation." Subsequent analysis of these PCs indicated an effect of RSV immunoprophylaxis on cell type composition of nasal brushed cells. Three CpG sites, cg18040241, cg08243963, and cg19555973 which are annotated to genes GLB1L2, SC5D, and BPIFB1, were differentially methylated at genome-wide significance, but were not associated with asthma.
Conclusion:
The study provides the first proof of concept that RSV immunoprophylaxis during infancy has long-term effects on nasal epigenetic signatures at age 6, relating to host sensory perception, epidermal growth factor receptor signaling, and adaptive immune responses.
