Editing Autoimmunity (section)

=== Genetic factors ===
Certain individuals are genetically susceptible to developing autoimmune diseases. This susceptibility is associated with multiple genes plus other risk factors. Genetically predisposed individuals do not always develop autoimmune diseases. Three main sets of genes are suspected in many autoimmune diseases.  These genes are related to:<ref>{{Cite journal |last1=Heward |first1=Joanne |last2=Gough |first2=Stephen C. L. |date=1997-12-01 |title=Genetic Susceptibility to the Development of Autoimmune Disease |url=https://portlandpress.com/clinsci/article/93/6/479/76820/Genetic-Susceptibility-to-the-Development-of |journal=Clinical Science |language=en |volume=93 |issue=6 |pages=479–491 |doi=10.1042/cs0930479 |pmid=9497784 |issn=0143-5221|url-access=subscription }}</ref>
* [[Immunoglobulins]]
* [[T-cell receptor]]s
* The [[major histocompatibility complex]]es (MHC).

The first two, which are involved in the recognition of antigens, are inherently variable and susceptible to recombination.  These variations enable the immune system to respond to a very wide variety of invaders, but may also give rise to [[lymphocyte]]s capable of self-reactivity.
* HLA DR2 is strongly positively correlated with [[systemic lupus erythematosus]], [[narcolepsy]]<ref name="pmid10984567">{{cite journal | vauthors = Klein J, Sato A | title = The HLA system. Second of two parts | journal = The New England Journal of Medicine | volume = 343 | issue = 11 | pages = 782–786 | date = September 2000 | pmid = 10984567 | doi = 10.1056/NEJM200009143431106 }}</ref> and [[multiple sclerosis]], and negatively correlated with DM Type 1.
* HLA DR3 is correlated strongly with [[Sjögren syndrome]], [[myasthenia gravis]], [[lupus erythematosus]], and [[type 1 diabetes mellitus]].
* HLA DR4 is correlated with the genesis of [[rheumatoid arthritis]], type 1 diabetes mellitus, and [[pemphigus vulgaris]].

Fewer correlations exist with MHC class I molecules.  The most notable and consistent is the association between HLA B27 and spondyloarthropathies like [[ankylosing spondylitis]] and [[reactive arthritis]]. Correlations may exist between [[Polymorphism (biology)|polymorphisms]] within class II MHC promoters and autoimmune disease.

The contributions of genes outside the MHC complex remain the subject of research, in animal models of disease (Linda Wicker's extensive genetic studies of diabetes in the NOD mouse){{clarify|What is an NOD mouse?|date=April 2024}}, and in patients (Brian Kotzin's linkage analysis of susceptibility to [[lupus erythematosus]]).

In recent studies, the gene [[PTPN22]] has emerged as a significant factor linked to various autoimmune diseases, such as Type I diabetes, rheumatoid arthritis, systemic lupus erythematosus, Hashimoto's thyroiditis, Graves' disease, Addison's disease, Myasthenia Gravis, vitiligo, systemic sclerosis, juvenile idiopathic arthritis, and psoriatic arthritis.<ref>{{cite journal | vauthors = Gregersen PK, Olsson LM | title = Recent advances in the genetics of autoimmune disease | journal = Annual Review of Immunology | volume = 27 | pages = 363–391 | date = 2009-01-01 | pmid = 19302045 | pmc = 2992886 | doi = 10.1146/annurev.immunol.021908.132653 }}</ref> PTPN22 is involved in regulating the activity of immune cells, and so variations in this gene can lead to dysregulation of the immune response, making individuals more susceptible to autoimmune diseases.<ref>{{Cite journal |last1=Chung |first1=Sharon A. |last2=Criswell |first2=Lindsey A. |date=January 2007 |title=PTPN22: Its role in SLE and autoimmunity |journal=Autoimmunity |language=en |volume=40 |issue=8 |pages=582–590 |doi=10.1080/08916930701510848 |issn=0891-6934 |pmc=2875134 |pmid=18075792}}</ref><ref>{{Cite journal |last1=Bottini |first1=Nunzio |last2=Peterson |first2=Erik J. |date=2014-03-21 |title=Tyrosine Phosphatase PTPN22: Multifunctional Regulator of Immune Signaling, Development, and Disease |journal=Annual Review of Immunology |language=en |volume=32 |issue=1 |pages=83–119 |doi=10.1146/annurev-immunol-032713-120249 |issn=0732-0582 |pmc=6402334 |pmid=24364806}}</ref>