Most of them are female, sometimes with a sex ratio of 9 women for 1 men, as in Lupus and Sjogren's Syndrome. Why this feminine predominance? For a long time, the only incirminated factor was female hormones (estrogens) but this explanation was insufficient because estrogens may even have, under certain circumstances, a protective anti-inflammatory role. In recent years, other interesting original explanations have been made. It is likely that the female X chromosome plays a major role because it carries many genes of immunity. The expression and regulation of these genes could be disrupted in major autoimmune diseases such as lupus.
Other phenomena such as fetal-maternal microchimerism, which is the exchange of cells (especially lymphocytes) during pregnancy through the placenta, may also play a role. So, systemic autoimmune diseases, such as lupus or localized forms of an organ (such as thyroiditis), preferentially affect women. For example, lupus or Sjögren's syndrome are female disorders in 90% of cases. This feminine predominance is an old mystery that is gradually elucidating.
Estrogen... the only the hormonal part of the mystery!
Estrogens are hormones with multiple immune effects that vary according to their type, concentration and target "tissues". They generally have a pro-inflammatory effect but can exert beneficial effects as in the bone where they oppose the osteoclastic resorption. There is an autoimmune disease, lupus, in which there is obviously an estrogen dependence as evidenced by aggravating pregnancy and sometimes the deleterious effect of the estroprogestative pill. In this disease, there may be tissue hyperoetrogenism that may be related to an increase in aromatase activity that transforms male hormones into estrogen. Estrogens are able to act directly on all cells of the immunity by activating inter alia autoreactive T and B lymphocytes in lupus while this phenomenon is not observed in healthy subjects.
Recently, it has also been shown that catabolites of estrogens called catecholoestrogens could have a toxic effect on the DNA, which is likely to make it immunogenic and to favor the appearance of anti-native anti-DNA antibodies characteristic of lupus. In other autoimmune diseases, estrogens probably also have immune effects but this has been less studied. which is likely to render it immunogenic and to promote the appearance of native anti-DNA autoantibodies characteristic of lupus. In other autoimmune diseases, estrogens probably also have immune effects but this has been less studied. which is likely to render it immunogenic and to promote the appearance of native anti-DNA autoantibodies characteristic of lupus. In other autoimmune diseases, estrogens probably also 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 encode immunity proteins, some of which have a very important role in autoimmune diseases (TLR7, IRAK1, CD40L). Thus, it has recently been observed that the only model of mouse lupus (mice) occurring in males is due to a duplication of the innate immunity genes called TLR7 involved in interferon synthesis. It is also interesting to observe that some of the rare genetic syndromes like Klinefelter Syndrome, which are "double X" (XXY) men, make as much lupus as women.
Women (XX) have 2 times more X chromosomes than men (XY)! The very ecumenical nature, created a phenomenon of equilibrium between the two sexes which is linked to the fact that the feminine cells will systematically inactivate one of the two X chromosomes randomly. This phenomenon of inactivation of the 2nd X chromosome is linked to methylation of chromosomal DNA. Recently, it has been shown that in lupus women, there is a defect of this inactivation by methylation. Thus, lupus women could therefore express the genes of immunity carried by their 2 X chromosomes, putting them in a state of "hyperimmunity". This very original phenomenon illustrates well the major role of epigenetics (that is to say the control of the
The role of microchimerism or the history of a transplacental fetal-maternal cell exchange!
It has been shown that during pregnancy, there was a "physiological" exchange of cells (especially lymphocytes) across the placenta. Surprisingly, it has been shown that these fetal cells could survive, after childbirth, for many years in women. thus, it was detected, in the circulation of a woman, the cells of her son born 29 years earlier. This phenomenon, called microchimerism, is physiological but may be important in autoimmune diseases. The role of microchimerism has been considered by analogy with a condition called graft-versus-host disease that occurs after a bone marrow or organ transplant, that is, in a chimerism (host / graft) situation. In case of transplant,
The role of microchimerism has been studied in scleroderma women with the detection of an excess of fetal cells in the blood and scleroderma skin lesions. However, it is unclear whether this microchemical phenomenon is the cause or consequence of autoimmune disease. Indeed, it can be speculated that fetal cells could exert a "repair" effect because they retained redifferentiation capabilities useful in tissue repair.
What is the role of microchimerism? Beneficial or adverse?
This remains to be determined but it is possible that this role is not the same in all autoimmune diseases because this phenomenon has not been observed in some of them such as Lupus.
The female predominance of most autoimmune diseases is a reality but the mechanisms that explain it are probably more complicated than previously thought. The discovered discoveries will certainly allow a better understanding of these diseases and perhaps to the identification of new therapeutic strategies and case to follow!
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