| Title: | Stratifying Multiple Sclerosis Susceptibility Risk: The Role of HLA-E*01 and Infectious Mononucleosis in a Population Cohort |
| Journal: | European Journal of Neurology |
| Published: | 7 Apr 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40192262/ |
| DOI: | https://doi.org/10.1111/ene.70131 |
Publication 14731
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Abstract
BACKGROUND: Epstein-Barr Virus (EBV) and its clinical manifestation, infectious mononucleosis (IM), are strongly linked to MS risk. A recent in vitro study suggests that HLA-E*01:03, in contrast to HLA-E*01:01, may protect against MS through more effective immune responses against EBV-infected B cells. However, the role of HLA-E*01 in MS remains unclear.</p>
METHODS: We investigated if HLA-E*01:01 was significantly associated with higher MS risk in individuals with a history of IM diagnosis, using 487,144 individuals from the UK Biobank's cohort. We estimated the interaction between HLA-E*01:01 and IM using Cox proportional hazard models, adjusting for demographics, smoking, childhood body size, older siblings, and MS-related HLA alleles (e.g., HLA-DRB1*15:01).</p>
RESULTS: HLA-E*01:01 allele alone was not significantly associated with IM or MS (p > 0.05). However, a significant interaction between HLA-E*01:01 and IM history was observed in relation to MS risk (p < 0.001). Specifically, MS risk was significantly higher in both HLA-E*01:01 heterozygotes (HR = 1.74 [95% CI: 1.36, 1.97], p < 0.001) and homozygotes (HR = 3.01 [95% CI: 1.81, 3.88], p < 0.001) with IM history, compared to HLA-E*01:03 homozygotes. Conversely, these associations were non-significant in individuals without IM history (p > 0.05). The estimated proportion of the combined risk attributable to interaction effects was 40% in HLA-E*01:01 heterozygotes and 65% in HLA-E*01:01 homozygotes.</p>
CONCLUSIONS: HLA-E*01:01 carriers diagnosed with IM are at significantly increased risk of MS, independently from other MS-related HLA alleles. This supports the hypothesis that HLA-E*01:01 may contribute to MS susceptibility due to weaker immune control over EBV infection. Incorporating HLA-E*01:01 into existing MHC-based MS risk models could then enhance personalized risk assessments in individuals with IM history.</p>
13 Keywords
- Adult
- Cohort Studies
- Female
- Genetic Predisposition to Disease
- HLA-E Antigens
- Histocompatibility Antigens Class I
- Humans
- Infectious Mononucleosis
- Male
- Middle Aged
- Multiple Sclerosis
- Risk Factors
- United Kingdom
8 Authors
- Andrea Nova
- Davide Gentilini
- Giovanni Di Caprio
- Sonia Bourguiba-Hachemi
- Nicolas Vince
- Pierre-Antoine Gourraud
- Luisa Bernardinelli
- Teresa Fazia
1 Application
| Application ID | Title |
|---|---|
| 93731 | Studying the impact of genetic variability, biochemical markers, environmental and lifestyle factors on Multiple Sclerosis onset risk and progression. |
Enabling scientific discoveries that improve human health