THE DOCTOR IS IN
OP / ED BY DR. ADIL MANZOOR
The body’s immune system is a lifesaver – literally. This system is a complex network of cells, proteins, and organs, constantly working to prevent foreign invaders from causing infections in the body. And the immune system is not just good at attacking and defending, as it also has a pretty good memory system.
Basically, when the immune system encounters an antigen (or foreign invader), it tries to attack it and just it, thereby protecting the body from any infection. If the immune system successfully eliminates the threat, it keeps a record of the antigen, which enables a faster and better response the next time the body comes across that antigen. We owe our continued existence to this system.
However, as with virtually every process in life, anomalies occur. In the case of the immune system, sometimes, the immune system is triggered even without antigens. When this occurs, the overactive immune cells enter panic mode and start attacking the host’s cells. As you can imagine, this is bad, and in some cases, very, very bad.
Conditions that arise from the body’s own immune system attacking its own cells are known as autoimmune disorders, and we currently know more than 100 of them. The common ones include lupus, type 1 diabetes, rheumatoid arthritis, psoriasis, Crohn’s disease, myasthenia gravis, ulcerative colitis, celiac disease, and inflammatory bowel disease.
There are many interesting – or disturbing, depending on how you want to view them – things about autoimmune conditions. For starters, they do not have a cure. In fact, some years ago, getting diagnosed with one of these conditions was considered as bad as a cancer diagnosis. However, developments in science have made most of them significantly more manageable. Secondly, we don’t know what causes them. There are several theories and postulations, but none is nowhere near definitive enough to determine its cause. Thirdly, and the most relevant to today’s discussion, about 80% of people with autoimmune conditions are women.
It’s strange, isn’t it, but autoimmune conditions are overwhelmingly more prevalent in women. In some conditions (hi, Sjögren syndrome), the ratio is even as bad as 19:1, comparing women and men. Usually, with a discrepancy this wide and with conditions this serious, you’d expect science to have all the right answers. Well, rather disappointingly, science cannot say for sure. This is definitely not for a lack of trying, as there have been several studies and some theories trying to justify this gender discrepancy, but, nope, we still don’t know why for sure.
Still, recent studies are starting to get very promising results on why women are eight times more likely to have these autoimmune conditions. Perhaps the most compelling and detailed theory so far comes from the is captured in the work of a group of scientists from Stanford University.
According to the study, the discrepancy is due to the double X chromosome in women. That, in itself, does not sound like an ingenious discovery, considering it’s the one, most fundamental differentiator between the two biological sexes. Let me explain, starting from the very beginning.
There are 23 pairs of chromosomes in any human. Of these, one pair informs biological sex and is consequently known as the sex chromosomes. As with other chromosomal pairs, the father and the mother each donate to the sex chromosomes. Men have an X and a Y chromosome, while women have two X chromosomes. In terms of function, the X chromosome is far more important to gene coding, being responsible for 800-900 genes coded to provide instructions for proteins. On the other hand, the Y chromosome is only responsible for coding around 50 genes.
During fertilization of the ovum, the mother and the father donate a sex chromosome to the eventual sex chromosome pair of the ovum and later the fetus. As the mother has a double X chromosome pair, she can only possibly donate an X chromosome. On the other hand, the father can donate either an X or a Y chromosome. If two X chromosomes are donated, a female child is conceived. Here comes the link to autoimmunity.
Because the X chromosome is responsible for encoding a lot of genes, having two X chromosomes will lead to an overexpression of proteins, which is very bad. To combat this, the body inactivates one of the X chromosomes inherited from the parents. The particular X chromosome that is inactivated is random, that is there is a 50% chance of the maternal and paternal chromosomes being inactivated.
The inactivation is carried out through the actions of a non-coding RNA molecule called Xist. While the gene for Xist is present on all X chromosomes, it can only be active on one chromosome in the pair at a time. The inactivation of the other X chromosome can lead to the generation of many proteins that bind directly to Xist or bind to proteins binding to Xist. Whichever the case, the study found that these collaborator proteins are linked to the generation of autoimmune conditions.
While this theory answers a lot of questions about the gender differences in autoimmunity, it causes more questions to be asked, particularly why not all women get autoimmune diseases and why some men still get autoimmune diseases. Quite simply, Xist alone is not enough to cause autoimmune conditions; environmental and other risk factors still matter. However, Xist is significant enough to greatly increase the odds of women getting the condition.
More research is still needed before more definitive claims can be made, and also a better understanding of how a cure for the conditions can be devised.
This article was written by Dr. Adil Manzoor, DO, a Board-Certified Internist & Board certified Pediatrician who works as a Hospitalist and Emergency Room Physician. He is also the current President of Garden State Street Medicine, a non-profit organization whose sole purpose is to provide free preventive and acute urgent care services for the homeless.
He is also the co-founder of his own unique medical practice, Mobile Medicine NJ; House Call Doctors. He is also currently pursuing an Executive MBA and a Master’s of Science in Healthcare Leadership at Samuel Curtis Johnson Graduate School of Management and the Weill Cornell Graduate School of Medical Sciences.
References
- https://med.stanford.edu/news/all-news/2024/02/women-autoimmune.html
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292717/
- https://www.washingtonpost.com/science/2024/02/01/why-women-have-more-autoimmune-diseases/
