Editing Sjögren's disease (section)

== Causes ==

While the exact cause is unclear, it is believed to involve a combination of [[Heredity|genetics]] and an [[environmental trigger]] such as exposure to a [[virus]] or [[bacterium]].<ref name=NIH2014Fact/> It can occur independently of other health problems or as a result of another [[connective tissue disorder]].<ref name=Ng2016>{{cite book|url=https://books.google.com/books?id=Axo9DAAAQBAJ&pg=PA10|title=Sjögren's Syndrome |last1= Ng| first1= Wan-Fai |date=2016|publisher=Oxford University Press|isbn=978-0-19-873695-0|pages=10–11| archive-url= https://web.archive.org/web/20160815195550/https://books.google.ca/books?id=Axo9DAAAQBAJ&pg=PA10|archive-date=15 August 2016|url-status= live}}</ref> Sjögren's disease may be associated with other autoimmune diseases, including [[rheumatoid arthritis]] (RA), [[systemic lupus erythematosus]] (SLE) or [[systemic sclerosis]]. The [[inflammation]] that results progressively damages the glands.<ref name=John2008/> Diagnosis is by biopsy of moisture-producing glands and [[blood tests]] for specific [[antibodies]].<ref name=Bri2016/> On [[biopsy]] there are typically [[lymphocyte]]s within the glands.<ref name=Bri2016/>

The cause of Sjögren's disease is unknown, but it may be the influence of a combination of genetic, environmental, and other factors, as is the case with many other autoimmune disorders.<ref name=borchers>{{cite journal | vauthors = Borchers AT, Naguwa SM, Keen CL, Gershwin ME | title = Immunopathogenesis of Sjögren's syndrome | journal = Clin Rev Allergy Immunol | volume = 25 | issue = 1 | pages = 89–104 | date = August 2003 | pmid = 12794264 | doi = 10.1385/CRIAI:25:1:89  | s2cid = 7098743 }}</ref> Around 20 autoantibodies could be involved.<ref>{{cite journal |last1=Martín-Nares |first1=Eduardo |last2=Hernández-Molina |first2=Gabriela |title=Novel autoantibodies in Sjögren's syndrome: A comprehensive review |journal=Autoimmunity Reviews |date=February 2019 |volume=18 |issue=2 |pages=192–198 |doi=10.1016/j.autrev.2018.09.003|pmid=30572138 |s2cid=58656692 }}</ref>

=== Genetics ===
The observation of high rates of autoimmune disorders in families with a history of Sjögren's disease is linked with a [[genetic predisposition]] to the disease.<ref name=Voulgarelis2010>{{cite journal | author = Voulgarelis M., Tzioufas A. G. | year = 2010 | title = Pathogenetic mechanisms in the initiation and perpetuation of Sjögren's syndrome | journal = Nature Reviews. Rheumatology | volume = 6 | issue = 9| pages = 529–537 | doi=10.1038/nrrheum.2010.118| pmid = 20683439 | s2cid = 8755126 }}</ref> Studies on the [[Polymorphism (biology)|polymorphisms]] of [[human leukocyte antigen]] [[HLA-DR|(HLA)-DR]] and [[HLA-DQ]] [[gene]] regions in Sjögren's patients show differential susceptibility to the disease as the result of different types of the resulting [[autoantibody]] production.<ref name=Voulgarelis2010/>

=== Hormones ===
Since Sjögren's disease is associated with a high prevalence in women, [[sex hormone]]s, especially [[estrogen]], are believed to affect [[Humoral immunity|humoral]] and [[Cell-mediated immunity|cell-mediated immune responses]] affecting susceptibility to the disease.<ref name=Voulgarelis2010/> [[Androgen]]s are generally considered to prevent autoimmunity.<ref name=delaleu>{{cite journal | vauthors = Delaleu N, Jonsson R, Koller MM | title = Sjögren's syndrome | journal = Eur. J. Oral Sci. | volume = 113 | issue = 2 | pages = 101–13 | date = April 2005 | pmid = 15819815 | doi = 10.1111/j.1600-0722.2004.00183.x }}</ref> Studies on mice models suggest [[estrogen deficiency]] stimulates presentation of [[autoantigens]], inducing Sjögren's-like symptoms.<ref name=Voulgarelis2010/>

=== Microchimerism ===
[[Microchimerism]] of fetal cells (offspring [[Lymphocyte|lymphoid cells]] in [[maternal circulation]]) may generate autoimmunity in women who have previously been [[pregnant]].<ref name=delaleu /><ref name="ReferenceB">{{cite journal | author = Whitacre C. C. | year = 2001 | title = Sex differences in autoimmune disease | journal = Nat. Immunol. | volume = 2 | issue = 9| pages = 777–780 | doi=10.1038/ni0901-777| pmid = 11526384 | s2cid = 6743550 }}</ref> Generation of an autoimmune potential via microchimerism may lead to a switch from a silent form of autoimmunity with age-dependent decrease in [[self-tolerance]].<ref name=delaleu />

=== Environment ===
[[Viral proteins]], engulfed [[molecules]], or degraded self-structures may initiate autoimmunity by [[molecular mimicry]] and increase the chances of Sjögren's disease development.<ref name=delaleu /> [[Epstein–Barr virus]], [[hepatitis C]], and [[human T-cell leukemia virus-1]] are among the most studied [[Pathogen|infectious agents]] in Sjögren's disease.<ref name=delaleu /> To date, no direct cause-and-effect relationship has been identified between these pathogens and the development of Sjögren's disease. Damaged self-structures targeted for [[apoptosis]] may be mistakenly exposed to the immune system, triggering autoimmunity in [[exocrine gland]]s, which are often prone to autoimmune responses.<ref name=delaleu />