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Mechanisms underlying sex differences in autoimmunity
Journal article   Open access   Peer reviewed

Mechanisms underlying sex differences in autoimmunity

DeLisa Fairweather, Danielle J. Beetler, Elizabeth J. McCabe and Scott M. Lieberman
The Journal of clinical investigation, Vol.134(18), e180076
09/17/2024
DOI: 10.1172/JCI180076
PMCID: PMC11405048
PMID: 39286970
url
https://doi.org/10.1172/JCI180076View
Published (Version of record) Open Access

Abstract

Autoimmune diseases are a leading cause of disability worldwide. Most autoimmune diseases occur more often in women than men, with rheumatic autoimmune diseases being among those most highly expressed in women. Several key factors, identified mainly in animal models and cell culture experiments, are important in increasing autoimmune disease in females. These include sex hormones, immune genes including those found on the X chromosome, sex-specific epigenetic effects on genes by estrogen and the environment, and regulation of genes and messenger RNA by microRNAs found in extracellular vesicles. Evidence is also emerging that viruses as well as drugs or toxins that damage mitochondria may contribute to increased levels of autoantibodies against nuclear and mitochondrial antigens, which are common in many autoimmune diseases. The purpose of this Review is to summarize our current understanding of mechanisms that may determine sex differences in autoimmune disease.
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