Could actively transcribed genes on Barr bodies be contributing to higher prevalence of autoimmune diseases in women?

And the answer is no… Or at least not how I hypothesized it while reading for my research paper. Allow me to explain:

A Barr body refers to the inactivated X chromosome present in female somatic cells. During development and through a yet to be determined mechanism, one of the X chromosome copies is selected to be compacted while the other becomes the primary chromosome for gene products to be transcribed and translated off. The name, X inactivation, can mislead people into believing that there is no active transcription off these X chromosome genes on Barr bodies. After having read that the X chromosome contains genes involved in innate and adaptive immune functions, I became excited and hoped to finally find an answer as to why more women were likely to develop multiple sclerosis than men. I hypothesized that the Barr body was producing more of these gene products, leading to a more active immune system and thus more autoimmune disease, but apparently there is more nuance than I was aware of.

            Autoimmune disease diagnosis is rising globally, and it is difficult decide if they are becoming more common or being diagnosed with more accuracy. Regardless, the paper I am reporting on primarily focuses on the odd disparity of certain autoimmune diseases in women over men. This increase can be seen as a 2:1 (or higher by some estimates) ratio of women to men who are diagnosed with multiple sclerosis. More shockingly, systemic lupus erythematosus (SLE) has a ratio of 9:1 or 10:1 ratio, giving support to the idea that there may be sex difference that increase the chances of developing these diseases. As a means of investigating these differences, an interesting solution was devised to studying females exhibiting a karyotype consistent with Turner’s syndrome (XO).

            If you were following in my footsteps, you also might have also been expected XO females to have less autoimmune diseases then 46, XX females. The exact opposite was found. XO females had double the autoimmune rate than 46, XX females, and 1.7 times higher rates of Hashimoto’s thyroidism, which is typically higher in men. Another interested observation from this same study was that women with Turner’s syndrome had 5 times higher rates of diabetes 1, which is an autoimmune disease typically seen at higher rates in men. These findings are topics for future research using techniques like genome-wide association studies (GWAS). The moral of the story is, don’t get too invested in one idea being the end all be all solution. The human body is complex and findings like these prove. The nice part is being wrong isn't always a dead end, but rather can lead to bigger and better questions that still require a lot more investigation. Plus, if the answer was that simple, it would have been discovered already. Stay hungry.

Sources:

Brooks WH, Renaudineau Y. Epigenetics and autoimmune diseases: the X chromosome-nucleolus nexus. Front Genet. 2015 Feb 16;6:22. doi: 10.3389/fgene.2015.00022. PMID: 25763008; PMCID: PMC4329817.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329817/