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Antibody response to common viruses and human leukocyte antigen-DRB1 in pediatric multiple sclerosis
Emmanuelle Waubant1, Ellen M Mowry, Lauren Krupp
1Regional Pediatric Multiple Sclerosis Center, University of California San Francisco, San Francisco, CA 94158, USA. Emmanuelle.waubant@ucsf.edu.
Background:
As remote infections with common herpes viruses are associated with modulation of the risk of multiple sclerosis (MS), we hypothesized that antibody concentrations against these viruses may further modify risk. As many common viruses are first encountered during childhood, pediatric MS offer a unique opportunity to investigate more closely their influence on susceptibility. Our aim was to determine if MS patients who were positive for these viruses had higher levels of antibodies to these viruses. We also assessed whether human leukocyte antigen (HLA)-DRB1*1501 genotype influenced viral antibody levels.
Methods:
Antibody response levels toward Epstein Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV)-1, and HLA-DRB1*1501 status were determined in pediatric MS patients (n=189) and controls (n=38). Multivariate analyses were used, adjusted for age, gender, race, ethnicity and use of disease-modifying therapies.
Results:
The antibody concentrations against EBV (Epstein-Barr nuclear antigen 1 (EBNA-1), viral capsid antigen (VCA) and early antigen (EA)), CMV and HSV-1 were similar between pediatric MS patients and controls positive for seroconversion against the virus of interest. EBNA-1 humoral responses were higher in HLA-DRB1 positive individuals (p=0.005) whereas other viral humoral responses were similar in HLA-DRB1 positive and negative individuals.
Conclusion:
Among those positive for EBNA-1, MS patients did not have higher levels of antibody response to EBNA-1: however, titers for EBNA-1 were higher in those who were HLA-DRB1 positive. This suggests that genotype might influence the humoral response to EBV. Whether other genotypes influence antibody response to other viruses remains to be determined.
Insights
Pediatric multiple sclerosis (MS) patients did not show higher antibody levels to common herpes viruses. However, human leukocyte antigen (HLA)-DRB1*1501 genotype was linked to higher Epstein-Barr nuclear antigen 1 (EBNA-1) antibody levels.
Area of Science:
- Neuroimmunology
- Virology
- Genetics
Background:
- Infections with common herpes viruses are linked to altered multiple sclerosis (MS) risk.
- Pediatric MS offers a unique window to study early viral influences on disease susceptibility.
- Investigating antibody concentrations against herpes viruses may reveal further risk modulation.
Purpose of the Study:
- To determine if pediatric MS patients positive for herpes viruses exhibit higher antibody levels.
- To assess the influence of human leukocyte antigen (HLA)-DRB1*1501 genotype on viral antibody levels in pediatric MS.
Main Methods:
- Antibody responses to Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV)-1 were measured.
- HLA-DRB1*1501 status was determined in 189 pediatric MS patients and 38 controls.
- Multivariate analyses adjusted for demographic factors and therapies were employed.
Main Results:
- Antibody concentrations against EBV, CMV, and HSV-1 were similar between pediatric MS patients and controls.
- Humoral responses to EBNA-1 were significantly higher in individuals positive for HLA-DRB1 (p=0.005).
- No significant differences in other viral antibody levels were observed based on HLA-DRB1 status.
Conclusions:
- MS patients did not exhibit higher EBNA-1 antibody titers compared to controls.
- HLA-DRB1 positivity correlated with higher EBNA-1 antibody titers, suggesting a genotype influence on EBV humoral response.
- Further research is needed to determine if other genotypes affect antibody responses to various viruses.
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