Xist RNA-Protein Complex Contributing to “Background Autoimmunity” in Women

The single biggest risk factor for autoimmune disease is being biologically a female and many explanations have been proposed as to why that is, among them sex hormones and the X chromosome with its large number of immune-related genes. Scientists have more recently pointed to another culprit—a molecule called Xist (X-inactive specific transcript) involved in the generation of antibodies to a woman’s own tissues. Xist is critical for the establishment of X chromosome inactivation, ensuring that females, like males, have one functional copy of the X chromosome in each body cell. Depending on the cell type, Xist in doing its job binds with different proteins to form ribonucleoprotein (RNP) complexes which, it is hypothesized can become visible to the immune system and misidentified as foreign and harmful, according to Diana Dou, PhD, a basic life research scientist at Stanford University. RNPs already exist that are clinical autoantigens for autoimmune disease, “so the Xist RNP may be eliciting a similar response from the immune system,” she says.   

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