This sheds light to gender-specific vulnerabilities.
Women exhibit a higher susceptibility to autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and lupus compared to men. Recent research provides a potential explanation deeply rooted in the genetic framework governing gender.
The intricate handling of the additional X chromosome in the female body emerges as a crucial factor. A report published in the journal Cell on February 1 delves into this phenomenon. This mechanism renders some women more prone to autoimmune diseases, elucidating why women constitute approximately 80% of autoimmune disease cases, where the immune system targets and attacks the body’s tissues and organs. The implications of this discovery extend to the prospect of improved detection and treatment for numerous autoimmune disorders.
For decades, immunologists and rheumatologists grappled with the puzzle of this gender-based discrepancy. Biological sex in mammals is determined by the presence of two X chromosomes in every female cell, while males have one X chromosome paired with a shorter Y chromosome. The X chromosome carries numerous active genes crucial for life, in contrast to the Y chromosome containing only a few.
To counter the heightened risk of producing a lethal double dose of proteins due to having two X chromosomes, nature deactivates one of them. This deactivation is facilitated by a special RNA called Xist, which attaches to the extra X chromosome, minimizing its genetic output. However, Xist also attracts proteins associated with autoimmune disorders, leading researchers to suspect a link between X-chromosome deactivation and the triggering of autoimmune diseases in women.
To test this hypothesis, researchers inserted the Xist gene into male lab mice predisposed to a lupus-like autoimmune disorder. Activation of the Xist gene resulted in the formation of protein clumps, similar to those observed in females. Further experiments demonstrated that male mice with an active Xist gene developed the lupus-like condition at rates approaching those of females when exposed to an irritant known to induce the disorder.
The study emphasizes the need for additional triggers, such as environmental factors, to activate autoimmune diseases. Despite not all female or Xist-activated male mice developing the disorder, the findings provide valuable insights. Researchers believe that Xist-linked protein clumps could serve as a basis for a test to determine an individual’s susceptibility to autoimmune diseases, offering a potential breakthrough in diagnosis and treatment. The research also highlights the impact of gender bias in medical research, underscoring the importance of considering female-specific factors in understanding autoimmune susceptibility.
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