ArticlePLoS genetics2020
Function of multiple sclerosis-protective HLA class I alleles revealed by genome-wide protein-quantitative trait loci mapping of interferon signalling.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- The Role of Interferon-α in Neurodegenerative Diseases: A Systematic Review.Journal of Alzheimer's disease : JAD · 2023Pooled it
- Genetic modification of obesity-associated disability progression in multiple sclerosis.Journal of neurology · 2026Article
- Interaction between smoking andMultiple sclerosis (Houndmills, Basingstoke, England) · 2026Article
- A unified framework for cell-type-specific eQTL prioritization by integrating bulk and scRNA-seq data.American journal of human genetics · 2025Article
- Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets.Neuron · 2025Review
- Genetics of immune response to Epstein-Barr virus: prospects for multiple sclerosis pathogenesis.Brain : a journal of neurology · 2024Article
- DNA Methylation signatures underpinning blood neutrophil to lymphocyte ratio during first week of human life.Nature communications · 2024Observational
- Head trauma results in manyfold increased risk of multiple sclerosis in genetically susceptible individuals.Journal of neurology, neurosurgery, and psychiatry · 2024Article
- The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity.Brain : a journal of neurology · 2024Review
- A novel machine learning-derived four-gene signature predicts STEMI and post-STEMI heart failure.Biomolecules & biomedicine · 2024Article
- Risk HLA Variants Affect the T-Cell Repertoire in Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Risk factors for multiple sclerosis in the context of Epstein-Barr virus infection.Frontiers in immunology · 2023Review
- Mimicking the brain: Epstein-Barr virus and foreign agents as drivers of neuroimmune attack in multiple sclerosis.Frontiers in immunology · 2023Review
- Evaluation of IL-1β and IL-6 Expression following EBNA-1 and BRLF-1 Peptide Treatment in Epstein-Barr Virus-Positive Multiple Sclerosis Patients.Intervirology · 2022Article
- Human immune diversity: from evolution to modernity.Nature immunology · 2021Review
- The CD8 T Cell-Epstein-Barr Virus-B Cell Trialogue: A Central Issue in Multiple Sclerosis Pathogenesis.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interferons (IFNs) are cytokines that are central to the host defence against viruses and other microorganisms. If not properly regulated, IFNs may contribute to the pathogenesis of inflammatory autoimmune, or infectious diseases. To identify genetic polymorphisms regulating the IFN system we performed an unbiased genome-wide protein-quantitative trait loci (pQTL) mapping of cell-type specific type I and type II IFN receptor levels and their responses in immune cells from 303 healthy individuals. Seven genome-wide significant (p < 5.0E-8) pQTLs were identified. Two independent SNPs that tagged the multiple sclerosis (MS)-protective HLA class I alleles A*02/A*68 and B*44, respectively, were associated with increased levels of IFNAR2 in B and T cells, with the most prominent effect in IgD-CD27+ memory B cells. The increased IFNAR2 levels in B cells were replicated in cells from an independent set of healthy individuals and in MS patients. Despite increased IFNAR2 levels, B and T cells carrying the MS-protective alleles displayed a reduced response to type I IFN stimulation. Expression and methylation-QTL analysis demonstrated increased mRNA expression of the pseudogene HLA-J in B cells carrying the MS-protective class I alleles, possibly driven via methylation-dependent transcriptional regulation. Together these data suggest that the MS-protective effects of HLA class I alleles are unrelated to their antigen-presenting function, and propose a previously unappreciated function of type I IFN signalling in B and T cells in MS immune-pathogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.