ArticleProceedings of the National Academy of Sciences of the United States of America2016
MHC class II super-enhancer increases surface expression of HLA-DR and HLA-DQ and affects cytokine production in autoimmune vitiligo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
58 citing papers in PubMed, 3 syntheses or guidelines pooled it, 100 citations in OpenAlex.
- Investigating the shared genetic architecture between inflammatory bowel disease and pancreatitis: a genome-wide cross-trait analysis.Molecular genetics and genomics : MGG · 2026Pooled it
- Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.Nature genetics · 2018Pooled it
- Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.Nature genetics · 2016Pooled it
- Selective control of HLA-DRB1 and HLA-DQA1 transcription through DR/DQ super enhancer microelements.Cell reports · 2026Article
- Molecular Pathogenesis of Vitiligo: Emerging Roles of Epigenetic Regulation.Biomolecules & therapeutics · 2026Review
- Emerging roles of circular RNAs and enhancer RNAs: new insights into the development and management of neurodegenerative disorders.Biomarker research · 2026Review
- Mendelian randomization reveals the associations between modifiable risk factors and intermediate phenotypes and spontaneous abortion.BMC pregnancy and childbirth · 2026Article
- Aberrant Enhancer Regulation, Phase Separation, and Autoimmune Diseases.Clinical reviews in allergy & immunology · 2025Review
- Downregulating human leucocyte antigens on mesenchymal stromal cells by epigenetically repressing a βNature biomedical engineering · 2024Article
- Inverse relationship between polygenic risk burden and age of onset of autoimmune vitiligo.American journal of human genetics · 2024Article
- Systemic lupus erythematosus genetics: insights into pathogenesis and implications for therapy.Nature reviews. Rheumatology · 2024Review
- From Phenotype to Molecules: Unveiling the Genetic and Immunological Bridges Between Autoimmune Diseases and Vitiligo.Clinical, cosmetic and investigational dermatology · 2024Article
- Variation within the non-coding genome influences genetic and epigenetic regulation of the human leukocyte antigen genes.Frontiers in immunology · 2024Review
- Single-cell transcriptomics reveals variations in monocytes and Tregs between gout flare and remission.JCI insight · 2023Article
- Mapping the dynamic genetic regulatory architecture of HLA genes at single-cell resolution.Nature genetics · 2023Article
- Comparison between qPCR and RNA-seq reveals challenges of quantifying HLA expression.Immunogenetics · 2023Article
- Mapping the dynamic genetic regulatory architecture ofmedRxiv : the preprint server for health sciences · 2023Article
- Spontaneous Reversal of Vitiligo, a Rare Phenomenon Reported in a Case in Saudi Arabia with an Insight into Metabolic Biochemical Derangements.Medicina (Kaunas, Lithuania) · 2023Article
- Simultaneous detection of DNA variation and methylation at HLA class II locus and immune gene promoters using targeted SureSelect Methyl-Sequencing.Frontiers in immunology · 2023Article
- Current Concepts of Vitiligo Immunopathogenesis.Biomedicines · 2022Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
Genetic risk for autoimmunity in HLA genes is most often attributed to structural specificity resulting in presentation of self-antigens. Autoimmune vitiligo is strongly associated with the MHC class II region. Here, we fine-map vitiligo MHC class II genetic risk to three SNPs only 47 bp apart, located within a predicted super-enhancer in an intergenic region between HLA-DRB1 and HLA-DQA1, localized by a genome-wide association study of 2,853 Caucasian vitiligo patients. The super-enhancer corresponds to an expression quantitative trait locus for expression of HLA-DR and HLA-DQ RNA; we observed elevated surface expression of HLA-DR (P = 0.008) and HLA-DQ (P = 0.02) on monocytes from healthy subjects homozygous for the high-risk SNP haplotype. Unexpectedly, pathogen-stimulated peripheral blood mononuclear cells from subjects homozygous for the high-risk super-enhancer haplotype exhibited greater increase in production of IFN-γ and IL-1β than cells from subjects homozygous for the low-risk haplotype. Specifically, production of IFN-γ on stimulation of dectin-1, mannose, and Toll-like receptors with Candida albicans and Staphylococcus epidermidis was 2.5- and 2.9-fold higher in high-risk subjects than in low-risk subjects, respectively (P = 0.007 and P = 0.01). Similarly, production of IL-1β was fivefold higher in high-risk subjects than in low-risk subjects (P = 0.02). Increased production of immunostimulatory cytokines in subjects carrying the high-risk haplotype may act as an "adjuvant" during the presentation of autoantigens, tying together genetic variation in the MHC with the development of autoimmunity. This study demonstrates that for risk of autoimmune vitiligo, expression level of HLA class II molecules is as or more important than antigen specificity.
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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.