It is said that autoimmune diseases are about 90% more common in female than male. E.g, female:male ratios in Autoimmune Diseases: Hashimoto's thyroiditis 10:1, Systemic lupus erythematosus 9:1,Sjogren's syndrome 9:1, Antiphospholipid syndrome-secondary 9:1 etc. What is the actual reason behind it?
Several hypotheses are known, of course the truth might be a combination of all of them. Hormonal differences certainly play a role (e.g. antiinflammaotry effect of androgens, proinflammatory effect of some estrogens). Differences in microbiota (however hen and egg is not clear) can also be correlated to gender bias, as well as gene-dosage effects, since some proteins encoded by e.g. X-chromosomes are thought to be a risk factor only when expressed high enough (female XX, male XY). Its supposedly a combination of all...
I have always thought that the fact that the female must not reject the fetus (which is partly foreign) contributes significantly to increased autoimmunity in females. Perhaps the factors that inhibit rejection, "encourage" pathways that permit autoimmune responses.
Dear Dr Mujibur Rahman,
Estrogen surely plays a role in autoimmune diseases. In the prototype disease Systemic lupus erythematosus (SLE) prevalence varies with age. In children where sex hormonal effects are minimal, the female-to-male ratio is 3:1. It increases to well over 10:1-15:1 in adults and again reduces post menopausal when estrogen levels come down.
The extra X chromosome too possibly plays a role (Rullo OJ, Ann Rheum Dis. 2013 Apr). At least 3 predisposing gene variants have been shown to be located on X chromosomes (IRAK1, MECP2, TLR7) . There is possibly an effect of gene dose too. In another study (Scofield RH. Arthritis Rheum. 2008;58(8):2511 ) it was shown that the frequency of Klinefelter's syndrome (47,XXY), though often subclinical, is increased in men with SLE by approximately 14-fold compared with its prevalence in men without SLE.
Like mentioned earlier by Georg Pongratz, its most likely multifactorial.
regards
Multiple factors are thought to contribute to a female bias in the development of certain autoimmune diseases (as noted by George, Hellen, and Shankar above). Notably, the female sex hormone estrogen through the estrogen receptor (ER) stimulates the expression of a set of interferon (IFN)- inducible genes (see link for a review below). Accordingly, in most of the diseases you noted, most (not all) female patients exhibit the "IFN-signature" in their peripheral blood mononuclear cells to varying extents. Further, activation of IFN-signaling in cells up-regulates the ER-signaling, thus, completing a positive feed-forward loop between the estrogen/ER and IFN-signaling in females.
Link: http://www.ncbi.nlm.nih.gov/pubmed/25155581
it is well know that sex hormones play a key role in the function of immune cells. The estrogens can enhance immunity while androgens and progesterone may down regulate. One of the most common examples is in SLE. in Lupus animal models, females develop disease earlier than males and die at younger age; oophorectomy delays the disease onset while castrated males suffer of early and more severe disease.
(Shoenfeld Y., et al. Gender Sex Hormones pregnancy and autoimmunity 2012).
I agree that the cause is probably multifactorial:genetics,estrogens,microbioma etc.
Abraham Garcia Kutzbach
Director of the Post graduate program in Rheumatology Francisco Marroquin University School of Medicine
In systemic sclerosis (SSc) the microchimerism is a proposed mechanism to partly explain the higher incidence of the disease in women, in which fetal or maternal allogeneic cells cross the placenta during pregnancy in a two-way traffic and persist in circulation and in the mother and fetus tissues, respectively. These grafted cells themselves may become activated by a second event, even after several decades, triggering a reaction similar to graft versus host manifested as SSc. The studies that support this theory is based on the meeting of fetal cells in the circulation of normal women many years after pregnancy and fetal DNA was found in women with SSc skin samples that had previously been a male fetus of pregnant women.
Also, another researcher Aida-Yasuoka et al imply estrogen in the development of autoimmune diseases, based on its ability to promote the survival and activation of B cells, facilitating self reactivity. Estradiol was identified as an inducer of fibronectin expression in skin fibroblasts from patients with SSc and pro-fibrotic effects of estradiol, as well as an increase in circulating levels of estradiol and estrone explain, at least in part, the higher frequency SSc in women. In a murine model of pulmonary fibrosis induced by bleomycin, pro-fibrotic role of estradiol was confirmed, since the female animals had more pronounced fibrotic response than males, which was attenuated after ovariectomy and marked with hormone replacement therapy.
Found the following link of interest: http://artemvitale.com/2015/08/why-women-get-more-autoimmune-diseases/
Please have a look at the following RG links.
Article The female-biased factor VGLL3 drives cutaneous and systemic...
Article Testosterone is an endogenous regulator of BAFF and splenic ...
The larger number of genes originating from the X chromosome creates a far greater possibility of a larger number of mutations occurring. This puts women at a greater risk for the development of autoimmune diseases solely due to women having two X chromosomes, whereas men possess only one.
Article The Prevalence of Autoimmune Disorders in Women: A Narrative Review
Please also see the RG link below.
Article Why women have more autoimmune diseases than men: An evoluti...
many of them trend to female preponderance you can say:
due to x chromosome inactivation
fetal microchimerism
hormonal fluctuation
pregnancy and immune rebound theory
hygiene theory can also take into account
RA , SLE, AITD.....etc
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