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A meta-analysis of interaction between Epstein-Barr virus and HLA-DRB1*1501 on risk of multiple sclerosis
Di Xiao1, Xingguang Ye1, Na Zhang1
1Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China.
Abstract:
Infection with Epstein-Barr virus (EBV) and HLA-DRB1*1501-positivity is a risk factor for multiple sclerosis (MS), but whether an interaction between these two factors causes MS is unclear. We therefore conducted a meta-analysis on the effect of the interaction between HLA-DRB1*1501 and EBV infection on MS. Searches of PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and the Wanfan databases through February 2015 yielded 5 studies that met the criteria for inclusion in the meta-analysis. EBV infection and HLA-DRB1*1501-positivity were dichotomized. The additive (S) and multiplicative interaction indexes (OR) between EBV infection and HLA-DRB1*1501 and their 95% confidence intervals (95%CI) were calculated for each study and then combined in a meta-analysis. EBV infection was significantly associated with MS (OR = 2.60; 95%CI, 1.48-4.59). HLA-DRB1*1501 was associated with a significantly increased risk of MS (OR, 3.06; 95%CI, 2.30-4.08). An interaction effect between EBV infection and HLA-DRB1*1501 on MS was observed on the additive scale (S, 1.43; 95%CI, 1.05-1.95, P = 0.023), but no interaction effect was observed on the multiplicative scale (OR, 0.86, 95%CI, 0.59-1.26). This meta-analysis provides strong evidence that EBV alone, HLA-DRB1*1501 alone or their interaction is associated with an elevated risks of MS.
Insights
Epstein-Barr virus (EBV) infection and HLA-DRB1*1501 positivity are each linked to increased multiple sclerosis (MS) risk. Their interaction shows an additive effect on MS development, suggesting a combined impact.
Area of Science:
- Neuroimmunology
- Genetics
- Infectious Diseases
Background:
- Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.
- Epstein-Barr virus (EBV) infection and the HLA-DRB1*1501 genetic marker are established risk factors for MS.
- The potential interaction between EBV infection and HLA-DRB1*1501 in MS pathogenesis requires further investigation.
Purpose of the Study:
- To conduct a meta-analysis evaluating the interaction effect of EBV infection and HLA-DRB1*1501 positivity on the risk of developing multiple sclerosis.
- To quantify the combined risk associated with these two factors.
Main Methods:
- A systematic literature search was performed across multiple databases (PubMed, Web of Science, CNKI, Wanfan) up to February 2015.
- Five relevant studies were included in the meta-analysis.
- Interaction effects were assessed using additive (S) and multiplicative (OR) indexes, with 95% confidence intervals (95%CI) calculated and combined.
Main Results:
- Both EBV infection (OR = 2.60, 95%CI: 1.48-4.59) and HLA-DRB1*1501 positivity (OR = 3.06, 95%CI: 2.30-4.08) were significantly associated with an increased risk of MS.
- A statistically significant additive interaction effect between EBV infection and HLA-DRB1*1501 on MS risk was observed (S = 1.43, 95%CI: 1.05-1.95, P = 0.023).
- No significant multiplicative interaction effect was found (OR = 0.86, 95%CI: 0.59-1.26).
Conclusions:
- This meta-analysis provides strong evidence that EBV infection and HLA-DRB1*1501 positivity independently increase the risk of MS.
- An additive interaction between EBV infection and HLA-DRB1*1501 suggests their combined presence contributes to elevated MS risk.
- These findings underscore the importance of considering both infectious and genetic factors in MS etiology.
