ArticleFrontiers in immunology2021
Gender and the Sex Hormone Estradiol Affect Multiple Sclerosis Risk Gene Expression in Epstein-Barr Virus-Infected B Cells.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Menopause and neurological disorders: a roadmap for research.Nature reviews. Neurology · 2026Review
- Why Is MS a More Frequent Complication of EBV Infection in Females?Immunological reviews · 2026Review
- EBV Triggers a Distinct Antiviral Response in HMC3 Cells.bioRxiv : the preprint server for biology · 2026Article
- Association between circulating selenium levels and arterial stiffness: a nationwide cross-sectional study.International journal of surgery (London, England) · 2026Article
- Sex-Related Differences in Lifestyle Factors Affecting Multiple Sclerosis Susceptibility and Disease Progression.Brain sciences · 2025Review
- A disease-specific convergence of host and Epstein-Barr virus genetics in multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- [Multiple sclerosis and the Epstein-Barr Virus: Current perspectives on their pathogenic mechanisms].Revista medica del Instituto Mexicano del Seguro Social · 2025Review
- Epstein-Barr virus as a potentiator of autoimmune diseases.Nature reviews. Rheumatology · 2024Review
- Economic and Social Standing of Individuals in Iran Diagnosed with Multiple Sclerosis.Archives of Iranian medicine · 2023Article
- Article
- Male and female are not the same: a multicenter study of static and dynamic functional connectivity in relapse-remitting multiple sclerosis in China.Frontiers in immunology · 2023Article
- The interaction between Epstein-Barr virus and multiple sclerosis genetic risk loci: insights into disease pathogenesis and therapeutic opportunities.Clinical & translational immunology · 2023Review
- KARAJ: An Efficient Adaptive Multi-Processor Tool to Streamline Genomic and Transcriptomic Sequence Data Acquisition.International journal of molecular sciences · 2022Article
- Construction of Immune-Related ceRNA Network in Dilated Cardiomyopathy: Based on Sex Differences.Frontiers in genetics · 2022Article
- Sex, aging and immunity in multiple sclerosis and experimental autoimmune encephalomyelitis: An intriguing interaction.Frontiers in neurology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple Sclerosis (MS) is a complex immune-mediated disease of the central nervous system. Treatment is based on immunomodulation, including specifically targeting B cells. B cells are the main host for the Epstein-Barr Virus (EBV), which has been described as necessary for MS development. Over 200 genetic loci have been identified as increasing susceptibility to MS. Many MS risk genes have altered expression in EBV infected B cells, dependent on the risk genotype, and are themselves regulated by the EBV transcription factor EBNA2. Females are 2-3 times more likely to develop MS than males. We investigated if MS risk loci might mediate the gender imbalance in MS. From a large public dataset, we identified gender-specific associations with EBV traits, and MS risk SNP/gene pairs with gender differences in their associations with gene expression. Some of these genes also showed gender differences in correlation of gene expression level with Estrogen Receptor 2. To test if estrogens may drive these gender specific differences, we cultured EBV infected B cells (lymphoblastoid cell lines, LCLs), in medium depleted of serum to remove the effects of sex hormones as well as the estrogenic effect of phenol red, and then supplemented with estrogen (100 nM estradiol). Estradiol treatment altered MS risk gene expression, LCL proliferation rate, EBV DNA copy number and EBNA2 expression in a sex-dependent manner. Together, these data indicate that there are estrogen-mediated gender-specific differences in MS risk gene expression and EBV functions. This may in turn contribute to gender differences in host response to EBV and to MS susceptibility.
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