ArticleBrain : a journal of neurology2018
Multiple sclerosis risk variants alter expression of co-stimulatory genes in B cells.
Article in Brain : a journal of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 citations in OpenAlex.
- Pleiotropy in the Genetic Predisposition to Rheumatoid Arthritis: A Phenome-Wide Association Study and Inverse Variance-Weighted Meta-Analysis.Arthritis & rheumatology (Hoboken, N.J.) · 2020Pooled it
- A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis.Nature communications · 2019Pooled it
- EBV reactivation priming of the peripheral immune system in multiple sclerosis relapse.Nature medicine · 2026Article
- Integrin β1 Demarks Precursors of Brain-Residing Antibody-Secreting Cells in Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- NEK2 regulates B cell function and the severity of experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2025Article
- 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
- Single-cell analysis of cerebrospinal fluid reveals common features of neuroinflammation.Cell reports. Medicine · 2025Article
- Oligodeoxynucleotide IMT504: Effects on Central Nervous System Repair Following Demyelination.Molecular neurobiology · 2024Article
- Silencing Immune Dialogue in Multiple Sclerosis.The New England journal of medicine · 2024Article
- Multiple sclerosis in a patient with Takayasu's Arteritis: A case report.Caspian journal of internal medicine · 2024Article
- The Plasticity of Immune Cell Response Complicates Dissecting the Underlying Pathology of Multiple Sclerosis.Journal of immunology research · 2024Review
- Advances in immune checkpoint-based immunotherapies for multiple sclerosis: rationale and practice.Cell communication and signaling : CCS · 2023Review
- Understanding humoral immunity and multiple sclerosis severity in Black, and Latinx patients.Frontiers in immunology · 2023Review
- Impaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis.The Journal of clinical investigation · 2022Article
- Gene-environment interactions increase the risk of pediatric-onset multiple sclerosis associated with ozone pollution.Multiple sclerosis (Houndmills, Basingstoke, England) · 2022Article
- Article
- The Effect of Peripheral Immune Cell Counts on the Risk of Multiple Sclerosis: A Mendelian Randomization Study.Frontiers in immunology · 2022Article
- Analysis of herpesvirus infection and genome single nucleotide polymorphism risk factors in multiple sclerosis, Volga federal district, Russia.Frontiers in immunology · 2022Article
- Cell-Type-Specific Gene Modules Related to the Regional Homogeneity of Spontaneous Brain Activity and Their Associations With Common Brain Disorders.Frontiers in neuroscience · 2021Article
- Elevated sCD40L in Secondary Progressive Multiple Sclerosis in Comparison to Non-progressive Benign and Relapsing Remitting Multiple Sclerosis.Journal of central nervous system disease · 2021Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
The increasing evidence supporting a role for B cells in the pathogenesis of multiple sclerosis prompted us to investigate the influence of known susceptibility variants on the surface expression of co-stimulatory molecules in these cells. Using flow cytometry we measured surface expression of CD40 and CD86 in B cells from 68 patients and 162 healthy controls that were genotyped for the multiple sclerosis associated single nucleotide polymorphisms (SNPs) rs4810485, which maps within the CD40 gene, and rs9282641, which maps within the CD86 gene. We found that carrying the risk allele rs4810485*T lowered the cell-surface expression of CD40 in all tested B cell subtypes (in total B cells P ≤ 5.10 × 10-5 in patients and ≤4.09 × 10-6 in controls), while carrying the risk allele rs9282641*G increased the expression of CD86, with this effect primarily seen in the naïve B cell subset (P = 0.048 in patients and 5.38 × 10-5 in controls). In concordance with these results, analysis of RNA expression demonstrated that the risk allele rs4810485*T resulted in lower total CD40 expression (P = 0.057) but with an increased proportion of alternative splice-forms leading to decoy receptors (P = 4.00 × 10-7). Finally, we also observed that the risk allele rs4810485*T was associated with decreased levels of interleukin-10 (P = 0.020), which is considered to have an immunoregulatory function downstream of CD40. Given the importance of these co-stimulatory molecules in determining the immune reaction that appears in response to antigen our data suggest that B cells might have an important antigen presentation and immunoregulatory role in the pathogenesis of multiple sclerosis.
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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.