WASHINGTON. Women are disproportionately affected by autoimmune diseases compared to men, and new research from Stanford University suggests that the reason may be linked to how the female body manages the extra X chromosome. The findings, reported Thursday, could potentially revolutionize the detection and treatment of a range of autoimmune disorders that have long posed challenges for diagnosis and treatment.
University of Pennsylvania immunologist E. John Wherry, not involved in the study, remarked, “This transforms the way we think about this whole process of autoimmunity, especially the male-female bias.”
Approximately 24 to 50 million Americans suffer from autoimmune disorders, including lupus, rheumatoid arthritis, multiple sclerosis, and others. Strikingly, about 80% of patients are women, a gender-based mystery that researchers have grappled with for decades.
One prevailing theory has focused on the X chromosome, given that females possess two X chromosomes while males have one X and one Y chromosome. The new research, published in the journal Cell, sheds light on the role of the extra X chromosome but in an unexpected manner.
The study reveals that a unique RNA, known as Xist, plays a crucial role in silencing one of the X chromosomes in each female cell to prevent an overdose of genes. Xist, pronounced like “exist,” attaches to the extra X chromosome, attracting proteins that form clumps and effectively silencing it.
Dr. Howard Chang, a dermatologist at Stanford, and his team identified nearly 100 proteins linked to skin-related autoimmune disorders in this process. Chang speculated that Xist, exclusive to women, might organize proteins in a way that triggers the immune system.
To test this, male lab mice were genetically modified to produce Xist without silencing their lone X chromosome. These mice, when triggered, developed lupus-like autoimmunity similar to females.
Chang emphasized that Xist alone couldn’t cause autoimmune diseases; a combination of genetic susceptibility and environmental triggers, such as infections or injuries, is likely needed. The team engineered mice susceptible to lupus and found that those producing Xist exhibited lupus-like conditions when triggered.
Beyond animal studies, the researchers examined blood samples from 100 patients, uncovering autoantibodies targeting Xist-associated proteins not previously linked to autoimmune disorders. This suggests that existing tests for autoimmunity, often developed using male cells, may have overlooked crucial aspects.
While more research is needed, the findings open new avenues for understanding and potentially diagnosing autoimmune diseases more efficiently. Dr. Wherry from the University of Pennsylvania noted, “Now we have at least one big part of the puzzle of biological context.” Stanford’s Chang envisions the possibility of interrupting the RNA process as a future investigation step.
Si Venus L Peñaflor ay naging editor-in-chief ng Newsworld, isang lokal na pahayagan ng Laguna. Publisher din siya ng Daystar Gazette at Tutubi News Magazine. Siya ay isa ring pintor at doll face designer ng Ninay Dolls, ang unang Manikang Pilipino. Kasali siya sa DesignCrowd sa rank na #305 sa 640,000 graphic designers sa buong daigdig. Kasama din siya sa unang Local TV Broadcast sa Laguna na Beyond Manila. Aktibong kasapi siya ng San Pablo Jaycees Senate bilang isang JCI Senator.
