Editing Autoimmunity (section)

==== Sex<!-- NOTE:  In these articles, "sex" refers to sex as used in studies that largely study cisgender people. Unfortunately most research does not confirm karyotype, and rarely studies minority genders. Please do not replace "sex" with "gender". A transwoman is not known to have the same risks as a ciswoman. --> ====
Most autoimmune diseases are ''[[sex-related diseases|sex-related]]; ''as a whole, women are much more likely to develop autoimmune disease than men. Being female is the single greatest risk factor for developing autoimmune disease than any other genetic or environmental risk factor yet discovered.<ref>{{cite journal | vauthors = Voskuhl R | title = Sex differences in autoimmune diseases | journal = Biology of Sex Differences | volume = 2 | issue = 1 | pages = 1 | date = January 2011 | pmid = 21208397 | pmc = 3022636 | doi = 10.1186/2042-6410-2-1 | doi-access = free }}</ref><ref name="pmid39286970">{{cite journal |vauthors=Fairweather D, Beetler DJ, McCabe EJ, Lieberman SM |title=Mechanisms underlying sex differences in autoimmunity |journal=J Clin Invest |volume=134 |issue=18 |pages= |date=September 2024 |pmid=39286970 |pmc=11405048 |doi=10.1172/JCI180076 |url=}}</ref> Autoimmune conditions overrepresented in women include: [[lupus]], [[primary biliary cholangitis]], [[Graves' disease]], [[Hashimoto's thyroiditis]], and [[multiple sclerosis]], among many others. A few autoimmune diseases that men are just as or more likely to develop as women include: [[ankylosing spondylitis]], [[type 1 diabetes mellitus]], [[granulomatosis with polyangiitis]], [[primary sclerosing cholangitis]], and [[psoriasis]].

The reasons for the sex role in autoimmunity vary. Women appear to generally mount larger inflammatory responses than men when their immune systems are triggered, increasing the risk of autoimmunity. Involvement of [[sex steroids]] is indicated by that many autoimmune diseases tend to fluctuate in accordance with hormonal changes, for example: during pregnancy, in the menstrual cycle, or when using oral contraception. A history of pregnancy also appears to leave a persistent increased risk for autoimmune disease. It has been suggested that the slight, direct exchange of cells between mothers and their children during pregnancy may induce autoimmunity.<ref>{{cite journal | vauthors = Ainsworth C | date = 15 November 2003 | url = https://www.newscientist.com/article.ns?id=mg18024215.100 | title = The Stranger Within | archive-url = https://web.archive.org/web/20081022063630/http://www.newscientist.com/article.ns?id=mg18024215.100| archive-date=2008-10-22 | journal = [[New Scientist]] | volume = 180 | issue = 2421 | page = 34 | url-access = subscription }} (reprinted  [http://www.katewerk.com/chimera.html here])</ref> This would tip the gender balance in the direction of the female.

Another theory suggests the female high tendency to get autoimmunity is due to an imbalanced [[X-inactivation|X-chromosome inactivation]].<ref>{{Cite web | vauthors = Kruszelnicki KS |date=2004-02-12 |title=Hybrid Auto-Immune Women 3 |url=https://www.abc.net.au/science/articles/2004/02/12/1002754.htm |access-date=2023-01-03 |website=www.abc.net.au |language=en-AU}}</ref> The X-inactivation skew theory, proposed by Princeton University's Jeff Stewart, has recently been confirmed experimentally in [[scleroderma]] and [[autoimmune thyroiditis]].<ref>{{cite journal | vauthors = Uz E, Loubiere LS, Gadi VK, Ozbalkan Z, Stewart J, Nelson JL, Ozcelik T | title = Skewed X-chromosome inactivation in scleroderma | journal = Clinical Reviews in Allergy & Immunology | volume = 34 | issue = 3 | pages = 352–355 | date = June 2008 | pmid = 18157513 | pmc = 2716291 | doi = 10.1007/s12016-007-8044-z }}</ref> Other complex X-linked genetic susceptibility mechanisms are proposed and under investigation.