ArticleJournal of autoimmunity2010
Mechanism by which HLA-DR4 regulates sex-bias of arthritis in humanized mice.
Article in Journal of autoimmunity, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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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.
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
41 citing papers in PubMed, 57 citations in OpenAlex.
- Murine and Humanized Mouse Models in Autoimmune Disease Research and Therapeutics Development.Biology · 2026Review
- Integrated analysis of sex differences in human dendritic cell, monocyte, and natural killer cell subsets.Frontiers in immunology · 2026Article
- Differences in autoimmune thyroid diseases between females and males: the result of a complex interconnection of factors.Endocrine · 2025Review
- Sex-Related Differences in Immunotherapy Toxicities: Insights into Dimorphic Responses.Cancers · 2025Review
- Gut Microbes as the Major Drivers of Rheumatoid Arthritis: Our Microbes Are Our Fortune!Microorganisms · 2025Review
- HLA diversity unveils susceptibility and organ-specific occurrence of second primary cancers: a prospective cohort study.BMC medicine · 2024Article
- Gut microbiota as a sensor of autoimmune response and treatment for rheumatoid arthritis.Immunological reviews · 2024Review
- Hormones and B-cell development in health and autoimmunity.Frontiers in immunology · 2024Review
- Article
- Mini-Review: Gut-Microbiota and the Sex-Bias in Autoimmunity - Lessons Learnt From Animal Models.Frontiers in medicine · 2022Review
- Sex bias in lymphocytes: Implications for autoimmune diseases.Frontiers in immunology · 2022Review
- The gut-joint axis in rheumatoid arthritis.Nature reviews. Rheumatology · 2021Review
- Sex and Gender Disparities in Melanoma.Cancers · 2020Review
- The effect of sex on immune responses to a homocitrullinated peptide in the DR4-transgenic mouse model of Rheumatoid Arthritis.Journal of translational autoimmunity · 2020Article
- Immunity to Influenza is dependent on MHC II polymorphism: study with 2 HLA transgenic strains.Scientific reports · 2019Article
- DLA class II haplotypes show sex-specific associations with primary hypoadrenocorticism in Standard Poodle dogs.Immunogenetics · 2019Article
- Sex Hormones Determine Immune Response.Frontiers in immunology · 2018Review
- Suppression of Inflammatory Arthritis by Human Gut-Derived Prevotella histicola in Humanized Mice.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
- Higher Estradiol and Lower Dehydroepiandrosterone-Sulfate Levels Are Associated with Pulmonary Arterial Hypertension in Men.American journal of respiratory and critical care medicine · 2016Article
- An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis.Genome medicine · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
HLA class II allele DRB1*0401 is associated with predisposition to Rheumatoid Arthritis in humans as well as collagen-induced arthritis in mice. Predominantly females develop arthritis in humans and DR4 transgenic mice; however the mechanism of sex-bias is still unknown. We have investigated the molecular basis by which DR4 is associated with sex-bias of arthritis. Here we show that differential antigen-specific immune mechanisms in DR4 male and female mice lead to increased susceptibility in female mice. B cells are hyperactive and present DR-restricted peptides robustly in females compared to males. Antigen-specific response showed that females produced B cell modulating cytokines like IL-13 while males produced IFNgamma. Male transgenic mice have higher number of T and B regulatory cells. An exogenous supply of 17beta estradiol in male mice led to enhanced expression of DR4 and antigen-specific response to DR4-restricted peptides. On the other hand, castration increased the incidence of arthritis. We propose that sex-bias in arthritis involves B cells and presentation of antigen by HLA-DR4 leading to activation of autoreactive cells and autoantibodies production in females, while regulatory B cells in males protect them from pathogenesis. The transgenic mice expressing RA susceptible haplotype simulate human RA and may be valuable to study gender differences observed in patients.
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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.