It has long been known in science that approximately 80% of autoimmune diseases (as a group of diagnoses) occur in women. And in certain specific autoimmune diseases, the overall incidence/prevalence in women is even higher than 80%. Scientists have been researching the reasons this occurs for decades. The amount of information related to this topic has been exploding over the past few decades, at an accelerating rate.

GENETICS

In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46. Twenty-two of these pairs, called autosomes, look the same in both males and females. The 23rd pair are the sex chromosomes (XX in women and XY in men). Each chromosome contains many genes. Genes are made up of DNA. DNA is the genetic code inside each cell.

The 2 most obvious differences between women and men that have been scientifically explored for decades to explain the higher prevalence of autoimmune disease in women are: 1) the hormone differences, and 2) the XX vs. XY (sex) chromosome difference between the 2 genders.

In addition to that, the differing cycles and levels of female hormones which occur at different times in a woman’s life are also investigated as relates to fluctuations in the typical age category when certain autoimmune diseases are most commonly diagnosed. Research is also focused on the changes in a woman’s immune system before, during and after pregnancy as relates to diagnosis of autoimmune diseases.

While most autoimmune diseases occur more frequently in women, research has conversely shown that certain autoimmune diseases do occur somewhat more often in men. Examples include: Ankylosing Spondylitis and Guillain-Barre Syndrome. Inflammatory Bowel Syndrome, Crohn’s Disease, Ulcerative Colitis, Celiac Disease, and Addison's Disease are other examples of diagnoses where the percentage needle moves a little more toward men. President John F. Kennedy had Addison’s Disease which was not made known while he was president. He was very thin and sickly as a young man and while in the Navy during WWII, till the drug CORTISONE was synthesized in the 1940’s and came out in the 1950’s-- which was a MAJOR game-changer for him before he ran for president. There are other interesting findings regarding the differences between men and women as relates to certain diagnoses. For example, men with Relapsing-Remitting MS tend to have a more rapid disease progression and more severe disability than women.  

A very recent discovery by an international team of researchers published in the prestigious scientific journal, CELL, may hold the most significant clue identified to date as to why more women have autoimmune diseases. They have identified a constellation of proteins they named “Xist RNA protein complex” which is only present in females. On page 742, they state, ”Every cell in a woman’s body has Xist….Our data further suggest a model where Xist contributes to several steps in the progression to autoimmune disease”.(1) They further describe epigenetic changes and gene expression as related to Xist which explains the presence and action of auto-antibodies, the hallmark of autoimmune diseases.  (Antibodies fight disease, auto-antibodies mistakenly attack the self “auto”.)   

EPIGENETICS

“Epi” is Greek prefix meaning at, on, to, upon, over, or beside.

Epigenetics is the new discipline in science to understand how genes become modified and affect evolution, organisms, disease, treatments, and cures. Cells use the same genetic information in different ways and this is the basis of epigenetic research. The epigenetic system controls how the genes in the DNA are used. Some genes can be turned off or on, either temporarily or permanently. And this is another finding of epigenetics.

The genetic code alone is not enough to describe what’s happening in a person because people that are genetically identical can appear quite different from one another. The “expression” of genes (what they do and how they do it) is switched on or off due to biochemical changes or reactions. It’s all about the EXPRESSION OF THE GENES which accounts for the differences seen even with the same DNA sequence.

Epigenetic actions, reactions, and consequences involves very complex biochemistry-- small chemical groups or individual proteins can be added to DNA, can be covered with other chemicals.

Environmental factors, the variances in when and where these occur can have lasting effects on a person’s biology. Other variables can influence the epigenetic system, such as diet/nutrition, significant & sustained emotional trauma, and others which are still  being identified.

Scientists are learning more and more about how these changes occur, the proverbial “NATURE vs. NURTURE” question.

________________________________________________________________

The Epigenetics Revolution: How Modern Biology Is Rewriting Our Understanding of Genetics, Disease, and Inheritance, Nessa Carey, Columbia University Press, 2011.

Recent Advances in the Genetics of Autoimmune Disease, Gregersen, P.K., Olsson, L. M., Annual Review of Immunology. 2009; 27: 363–391.

doi: 10.1146/annurev.immunol.021908.132653

Why Are Women and Men So Different in Autoimmune Disease? Lowe, D., Science, July, 14, 2021.

https://www.science.org/content/blog-post/why-are-women-and-men-so-different-autoimmune-disease 

Why autoimmune disease is more common in women: X chromosome holds clues, Elie Dolgin, Nature, Feb 2024.

https://www.nature.com/articles/d41586-024-00267-6

(1) Xist ribonucleoproteins promote female sex-based autoimmunity. Dou, D., Yanding, Z., Belk, J., Wutz, A, Utz, P., Chang, H. Cell, Feb. 1, 2024. Elsevier Inc.  

https://doi.org/10.1016/j.cell.2023.12.037