Most are women, sometimes with a gender ratio of 9 women to 1 man, as in Lupus and Sjogren’s Syndrome. Why this female dominance? For a long time only female hormones (estrogen) were exposed, but this explanation was insufficient, since estrogen can even have an anti-inflammatory protective function under certain circumstances. Other interesting and original explanations have been made in recent years. It is likely that the female X chromosome plays an important role as it carries many immunity genes. The expression and regulation of these genes could be disrupted in important autoimmune diseases such as lupus.
Other phenomena such as fetal-maternal microchimerism, i.e. the exchange of cells (especially lymphocytes) by the placenta during pregnancy, can also play a role. Systemic autoimmune diseases such as lupus or localized forms of an organ (such as thyroiditis) preferentially affect women. Lupus or Sjogren’s syndrome, for example, are female diseases in 90% of cases. This female dominance is an old mystery that is gradually being cleared up.
Estrogen… the only the hormonal part of the mystery!
Estrogens are hormones that have multiple immune effects that vary depending on the type, concentration, and target tissue. They generally have an inflammatory effect, but can have beneficial effects, for example in the bone, where they counteract osteoclastic resorption. There is an autoimmune disease, lupus, which is obviously dependent on estrogen, which shows in worsening pregnancy and sometimes in the harmful effects of the estrogen-progestogen pill. Tissue hyperetrogenism may be present in this disease, which may be related to an increase in aromatase activity, which converts male hormones into estrogen. Estrogens can act directly on all immune cells by activating, among other things, the T and B lymphocytes that are autoreactive in lupus, whereas this phenomenon is not observed in healthy volunteers.
It has also recently been shown that estrogen catabolites called catecholic estrogens can have a toxic effect on DNA, making it likely immunogenic and promoting the appearance of anti-native anti-DNA antibodies characteristic of DNA. In other autoimmune diseases, estrogen is likely to have immune effects as well, but this has been less studied. making it likely immunogenic and promoting the appearance of native anti-DNA autoantibodies that are characteristic of lupus. In other autoimmune diseases, estrogen is likely to have immune effects as well, but this has been less studied. making it likely immunogenic and promoting the appearance of native anti-DNA autoantibodies that are characteristic of lupus. In other autoimmune diseases, estrogen is also likely to have immune effects, but this has been less studied.
The X chromosome is very immune. An attractive genetic explanation (epi) genetic!
The X chromosome carries many genes (several hundred) that code for immune proteins, some of which play a very important role in autoimmune diseases (TLR7, IRAK1, CD40L). For example, it was recently observed that the only model of mouse (mouse) lupus that occurs in men is due to a duplication of genes of innate immunity called TLR7, which are involved in the synthesis of interferons. It’s also interesting to note that some of the rare genetic syndromes like Klinefelter’s syndrome who are “double X” men (XXY) cause as much lupus as women.
Women (XX) have twice as many X chromosomes as men (XY)! The very ecumenical nature has created a phenomenon of equilibrium between the two sexes, which is related to the fact that female cells systematically inactivate one of the two X chromosomes accidentally. This phenomenon of inactivation of the 2nd X chromosome is linked to the methylation of the chromosomal DNA. It was recently shown that there is a defect in this methylation inactivation in women with SLE. Thus, women with SLE could therefore express the immunity genes carried on their 2 X chromosomes, placing them in a state of “hyperimmunity”. This very original phenomenon clearly illustrates the main role of epigenetics (i.e. the control of
The role of microchimerism or the history of a transplacental fetal-maternal cell exchange!
It has been shown that during pregnancy a “physiological” exchange of cells (especially lymphocytes) takes place across the placenta. Surprisingly, these fetal cells have been shown to survive in women for many years after birth. The cells of her son, who was born 29 years earlier, were detected in a woman’s circulation. This phenomenon, known as microchimerism, is physiological, but it can be important in autoimmune diseases. The role of microchimerism has been viewed by analogy with a condition known as graft-versus-host disease that occurs after a bone marrow or organ transplant; H. in a chimeric (host / graft) situation. In the case of a transplant,
The role of microchimerism has been studied in women with scleroderma through the detection of excess fetal cells in the blood and scleroderma skin lesions. However, it is not clear whether this microchemical phenomenon is the cause or consequence of an autoimmune disease. Indeed, it is believed that the fetal cells might have a “repairing” effect since they retain the redifferentiating capacities useful for tissue repair.
What is the role of microchimerism? Beneficial or adverse?
This has yet to be clarified, but it is possible that this role is not the same in all autoimmune diseases as this phenomenon has not been observed in some of them, such as lupus.
The female dominance of most autoimmune diseases is a reality, but the mechanisms behind it are believed to be more complicated than previously thought. The discoveries made will certainly allow a better understanding of these diseases and possibly the identification of new therapeutic strategies and cases!