ArticleJournal of autoimmunity2013
Overexpression of X-linked genes in T cells from women with lupus.
Article in Journal of autoimmunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 4 of them syntheses that pooled it.
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Who cites it
124 citing papers in PubMed, 4 syntheses or guidelines pooled it, 221 citations in OpenAlex.
- An Update on the Pathogenesis of Skin Damage in Lupus.Current rheumatology reports · 2020Pooled it
- Meta-analysis of GWAS on both Chinese and European populations identifies GPR173 as a novel X chromosome susceptibility gene for SLE.Arthritis research & therapy · 2018Pooled it
- Biosemantics guided gene expression profiling of Sjögren's syndrome: a comparative analysis with systemic lupus erythematosus and rheumatoid arthritis.Arthritis research & therapy · 2017Pooled it
- Cytokine gene considerations in giant cell arteritis: IL10 promoter polymorphisms and a review of the literature.Clinical reviews in allergy & immunology · 2014Pooled it
- Sex-dependent mechanisms in rheumatic diseases.Nature reviews. Rheumatology · 2026Review
- The X Factor in Immunity: Sex Differences Shaped by the X Chromosome.Immunological reviews · 2026Review
- Knowledge gaps and research priorities to understand sex differences in immunity.PLoS biology · 2026Review
- Suppression of CSF2RA macrophage polarisation impacts pathological cardiac remodelling in mice.Scientific reports · 2026Article
- Grand challenges in sex differences in immunology: problems the field must solve before biological sex can guide clinical practice.Frontiers in immunology · 2026Article
- Estrogen Modulation of B Cell Immunity: Implications for HIV Control and Therapeutic Strategies.Comprehensive physiology · 2025Review
- X-linked transcriptome dysregulation across immune cells in systemic lupus erythematosus.Biology of sex differences · 2025Article
- Treat-To-Target: Emergence of Second-Generation CD40L Inhibitors for Treatment of SLE-Identifying Beneficial Patient Candidates for CD40L Inhibitors in a Cross-Sectional SLE Cohort.Scandinavian journal of immunology · 2025Article
- Sex Bias in Systemic Sclerosis: from Clinical to Immunological Differences.Clinical reviews in allergy & immunology · 2025Review
- More X's, more problems: how contributions from the X chromosomes enhance female predisposition for autoimmunity.Current opinion in immunology · 2025Review
- Sex differences in disease: sex chromosome and immunity.Journal of translational medicine · 2024Review
- The role of protein O-GlcNAcylation in diabetic cardiomyopathy.Biochemical Society transactions · 2024Review
- Identifying X-chromosome variants associated with age-related macular degeneration.Human molecular genetics · 2024Article
- Female-bias in systemic lupus erythematosus: How much is the X chromosome to blame?Biology of sex differences · 2024Review
- The impact of sex on HIV immunopathogenesis and therapeutic interventions.The Journal of clinical investigation · 2024Review
- Sex difference in human diseases: mechanistic insights and clinical implications.Signal transduction and targeted therapy · 2024Review
64 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Women develop lupus more frequently than men and the reason remains incompletely understood. Evidence that men with Klinefelter's Syndrome (XXY) develop lupus at approximately the same rate as women suggests that a second X chromosome contributes. However, since the second X is normally inactivated, how it predisposes to lupus is unclear. DNA methylation contributes to the silencing of one X chromosome in women, and CD4+ T cell DNA demethylation contributes to the development of lupus-like autoimmunity. This suggests that demethylation of genes on the inactive X may predispose women to lupus, and this hypothesis is supported by a report that CD40LG, an immune gene encoded on the X chromosome, demethylates and is overexpressed in T cells from women but not men with lupus. Overexpression of other immune genes on the inactive X may also predispose women to this disease. We therefore compared mRNA and miRNA expression profiles in experimentally demethylated T cells from women and men as well as in T cells from women and men with lupus. T cells from healthy men and women were treated with the DNA methyltransferase inhibitor 5-azacytidine, then X-linked mRNAs were surveyed with oligonucleotide arrays, and X-linked miRNA's surveyed with PCR arrays. CD40LG, CXCR3, OGT, miR-98, let-7f-2*, miR 188-3p, miR-421 and miR-503 were among the genes overexpressed in women relative to men. MiRNA target prediction analyses identified CBL, which downregulates T cell receptor signaling and is decreased in lupus T cells, as a gene targeted by miR-188-3p and miR-98. Transfection with miR-98 and miR-188-3p suppressed CBL expression. The same mRNA and miRNA transcripts were also demethylated and overexpressed in CD4+ T cells from women relative to men with active lupus. Together these results further support a role for X chromosome demethylation in the female predisposition to lupus.
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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.