Epigenetics of autoimmune disorders: Difference between revisions
Aspillutla (talk | contribs) Fleshed out paragraph about Graves' disease. Graves disease shares much (in relation to epigenetics) with Hashimoto's thyroiditis, and that's reflected in the paragraph. |
Aspillutla (talk | contribs) Fleshed out Celiac Disease section |
||
| Line 35: | Line 35: | ||
=== Celiac Disease === |
=== Celiac Disease === |
||
Celiac disease is a disease in which the small intestine is damaged in those whose bodies are unable to process gluten. |
Celiac disease is a disease in which the small intestine is damaged in those whose bodies are unable to process gluten. Celiac disease is an autoimmune disorder in which exposure to glutinous foods like wheat and rye is the primary environmental factor. Several epigenetic mechanisms have been found to be implicated in Celiac disease. A high rate of DNA methylation of CpGs contributes to the development of small bowel adenocarcinomas, which are malignant tumors, in individuals with Celiac disease. Furthermore, unusual methylation in the genes involved in the core NF-κB pathway is implicated in the pathogenesis of Celiac disease. There are also allele-specific gene methylations that impact phenotype in such a way that it can lead to Celiac disease, thus involving allele-specific methylation in Celiac disease predisposition. Additionally, an increase in histone acetylation, specifically H3K27ac, has been found in Celiac disease biopsies.<ref name=":9">{{Cite journal |last=Gnodi |first=Elisa |last2=Meneveri |first2=Raffaella |last3=Barisani |first3=Donatella |date=2022-01-28 |title=Celiac disease: From genetics to epigenetics |url=https://www.wjgnet.com/1007-9327/full/v28/i4/449.htm |journal=World Journal of Gastroenterology |volume=28 |issue=4 |pages=449–463 |doi=10.3748/wjg.v28.i4.449 |issn=1007-9327 |pmc=PMC8790554 |pmid=35125829}}</ref> Furthermore, the regulation of certain microRNAs, which are a type of non-coding RNA, differs significantly in individuals with Celiac disease compared to control individuals without Celiac disease. This significant difference was found to come in the form of downregulation of some microRNAs and upregulation of others.<ref>{{Cite journal |last=Dieli-Crimi |first=Romina |last2=Cénit |first2=M. Carmen |last3=Núñez |first3=Concepción |date=2015-11 |title=The genetics of celiac disease: A comprehensive review of clinical implications |url=https://linkinghub.elsevier.com/retrieve/pii/S0896841115300044 |journal=Journal of Autoimmunity |language=en |volume=64 |pages=26–41 |doi=10.1016/j.jaut.2015.07.003}}</ref> |
||
=== Addison's Disease === |
=== Addison's Disease === |
||
Revision as of 21:45, 18 March 2022
Sandbox of Emily Breach, Aamani Pillutla, Oliver Myers
Epigenetics plays a major role in the onset of autoimmune diseases like multiple sclerosis, lupus, and rheumatoid arthritis. Developing a better understanding of these conditions in the context of epigenetics offers hope in potential development of new therapeutic treatment options[1]. In this article, we would explore how histone modifications such as methylation and acetylation of the genome produce the phenotypes of these diseases. Interestingly, recent research has shown that across the genomes of those with these conditions, they share similar modifications in the non-coding region of the RNA rather than the portion that is transcribed and translated into a protein[1]. As well as discussing these commonalities across disorders, we could next explore how epigenetics plays a role in the onset of these diseases since they have both a genetic and an environmental component. We would explore how the epigenome plays as an intermediary in regulating the way that the immune system responds to environmental hazards such as UV rays and oxidative stress[2] and then venture into the specific of each individual condition. As a start, I have listed out 12 common autoimmune diseases, particularly ones relating to endocrinology, neurology, and connective tissue. Under each disease heading we will explore which epigenetic modifications are associated with these diseases and how they are casual with their associated symptoms. We will also explore what types of treatments currently exist for these conditions briefly and what way treatment is going towards in terms of therapeutics that target the epigenome. I'm very open to any feedback from those interested in this project. Under each section I have cited a few modifications associated with each of these conditions and have included review articles that we can use to write up each section. This would be an awesome group to join if you're interested in pursuing medicine or if you have an autoimmune disease like myself and would like to better understand your condition!
What would we write about?: We we would start with a section briefly brushing up on epigenetic modulation and how the immune system works such as CD4 T cells and innate vs acquired immunity and how this is modulated by the epigenome[3]. We'd then discuss current technologies being utilized to study this and go into how in the past, researchers have had difficulty with identifying the SNP mutations in the DNA responsible for these conditions as well as elucidating how these mutations alter normal cellular pathway and lead to pathogenesis and then discuss how research using GWAS (genome-wide association studies) has begun to utilize computer modeling to sift through this data and identify specific casual mutations. For example, Farh et al utilized a computational model to identify SNPs for 21 different auto immune diseases and after looking at loci associated with autoimmunity, they identified 12% of causal SNPs for these conditions[4]. We can also describe how we are advancing as far as our understanding of epigenetic modifications in the genome and how this is effecting the way these conditions are being treated. After this, we would go into types of modifications and discuss ones common across a group of conditions. Here, we can discuss how human leukocyte antigen(HLA) is heavily linked to the pathogenesis of autoimmune disorders as well, so here I would also include a general discussion of how this plays a key role, as well as explore how non-HLA genes such as IRF8, OLIG3/TNFAIP3, IL23R, IL2RA, IRF8, IRF5, PTPN22, ICAM3, STAT4, and BANK1 are involved across different conditions[2] . Lastly under each disease we will go into defining the diseases, modifications specific to these diseases and the causal role they play in the pathogenesis and potential treatments in relation to the epigenome. If members prefer, this article can instead be broken down instead by types of condition like the epigenetic of connective tissue autoimmune diseases and epigenetic of endocrinological autoimmune etc.
Epigenetics of Autoimmune Disorders
Autoimmune diseases are a diverse class of diseases characterized by a person's immune system attacking their healthy cells. Autoimmune diseases include Lupus, Rheumatoid Arthritis, and Multiple Sclerosis to name a few.[5] Many different factors can account for the onset of autoimmune disorders, however there is a large epigenetic component particularly regarding how alterations in methylation patterns plays a role in these diseases' pathology. Additionally, dysregulation of non-coding RNA and histone modification are key players in exploring the epigenetics underlying these diseases[2] . Here also discuss evidence comparing prevalence of the diseases compared between dizygotic and monozygotic twins[2] . Also discuss how autoimmune diseasses are more common in women since immune system-related genes fall on the X-chromosome and X-inactivation that occurs in females can lead to silencing of genes essential for immune function [6] .
Hmm. Your last sentence is interesting but counter intuitive to me. Why should X inactivation make it more common? The allele frequency on the X is fixed in the population but females have a "choice" between two X's whereas males have no "choice". In females there is at least the chance that one part of the immune system will use one X and the other part the other X. This sort of thing with respect to blood, musculature, and the nervous system accounts for the reason that hemophilia, muscular dystrophy, and X-linked CNS disorders are more common and problematic in males than in females. So, figure this out. Happy for you to be correct and I want you to explain it very carefully because there might be something new for me to learn.
Autoimmune Diseases and DNA Methylation
Hypomethylation, a loss of DNA methylation, particularly hypomethylation of DNA promoters is heavily associated with multiple different autoimmune disorders, specifically rheumatoid arthritis and systemic lupus erythematosus; <-- I really dislike unneeded abbreviations. This is the best way to lose your audience. Changed by Aamani from abbreviations 03/17 9:27 Next discuss procainamide and hydralazine induced lupus like condition an d how this relates to hypomethylation as underlying cause of many autoimmune diseases[4]. Here we would also discuss circRNA and how it is a regulator of methylation and the immune system and how this is tied into many autoimmune conditions[7] Next write about hypermethylation and its role in autoimmune diseases like Type 1 Diabetes. Include research from the Farh et al paper because this is a big deal in the epigenetic research as far as identifying causal loci via GWAS and iChip analysis[4].
Multiple Sclerosis (MS)
Multiple Sclerosis is an autoimmune disease characterized by neurodegeneration, causing damage to the myelin sheath of neurons leading to weakness, pain, and vision loss; role of miRNA[5]. Discuss modifications described in these articles:[8], [9] . We could also try and include more neurodegenerative autoimmune diseases in this article.
Systemic Lupus Erythematosus(SLE)
Systemic lupus is the most common form of lupus and is a condition in which the immune system attacks healthy bodily tissue. There is a strong link between SLE and epigenetic modifications and here we will discuss how hypomethylation of E1B of CD5 in B cells is associated with this diseases pathology[5] . We will also discuss how this diseases is characterized by X chromosome inactivation, noncoding RNA, demethylation of SLE CD4+ T cells with detail and an explanation of the underlying biochemical mechanisms[2]
Discoid Lupus Erythematosus (DLE)
Discoid lupus is a cutaneous autoimmune condition in which the immune system attacks healthy tissue and is presented by lesions on the skin, inflammation, and rashes. Here we will explore how differential expression of lncRNAs and circRNAs identified in a study by Xuan et alter the mucosa a key part in this disease[7].
Rheumatoid Arthritis (RA)
Rheumatoid arthritis is a degenerative autoimmune disease that damages and causes inflammation in a patients joint. It is characterized by hypomethylation of synovial cells and CpG island hypomethylation[5] . Patients with RA often display anti-cyclic citrullinated peptide (anti-CCP) antibodies and have hypomethylation of the retrotransposon gene L1, and decreased methylation at the Il6 and ERa promoter[10]. Also discuss modifications in this article: [11].
You note a number of genes that show changes. Is there evidence that these are causative or is the change merely assoicated with rheumatoid arthritis. Perhaps, a response to it.
Type I Diabetes
Type I diabetes is an endocrinological disease in which the immune system’s T cells attack the beta cells of the pancreas, disrupting the production of insulin. Type I diabetes is characterized by global hypermethylation[5]. The demethylation of certain proteins is implicated in Type I diabetes such as HOXA9, a transcription factor whose demethylation has been reported in Type I diabetes. Additionally, increased DNA methylation in the Foxp3 promoter region has been observed in Type I diabetes. The increased DNA methylation of the Foxp3 promoter region leads to a reduction in the frequency of regulatory T cells, which suppress immune responses in the body, in the blood of Type I diabetics[10]. Increased DNA methylation variability in immune effector cells in Type I diabetes has shown the involvement in DNA methylation in other processes related to Type I diabetes’ pathogenesis as well[12].
Hashimoto's Thyroiditis
Hashimoto's thyroiditis is an endocrine disease in which a patient’s immune system attacks their thyroid gland. Hashimoto’s thyroiditis usually manifests via hypothyroidism, which is characterized by “lymphocytic infiltration of the thyroid and the production of thyroid autoantibodies”[6]. Research suggests a strong genetic susceptibility when it comes to autoimmune thyroid diseases like Hashimoto’s thyroiditis, and an epigenetic involvement in the pathology of Hashimoto’s thyroiditis. In association with autoimmune thyroid diseases such as Hashimoto’s thyroiditis, a change in histone methylation patterns in the thyroglobulin (Tg) promoter has been found in a genetic variant, wherein Tg is a thyroid-specific gene. In specific, the transcription factor IRF-1 binds to the Tg promoter exclusively only when the disease-associated variant is present. This binding of IRF-1 to Tg is impacted by modulations in histone methylation patterns. Something of note here is that in the Tg promoter, the susceptibility allele allows the binding of IRF-1 in the case of a viral infection, pointing to a potential environmental factor on the development of Hashimoto’s thyroiditis, rather than attributing epigenetic modifications restrictively to genetic sources.[6] In addition to histone methylation, skewed X chromosome inactivation has been found to be implicated in autoimmune thyroid diseases (specifically Hashimoto’s thyroiditis and Graves’ disease), therefore indicating that the level of X chromosome inactivation in females is an important factor in the risk of developing autoimmune thyroid diseases[13].
Celiac Disease
Celiac disease is a disease in which the small intestine is damaged in those whose bodies are unable to process gluten. Celiac disease is an autoimmune disorder in which exposure to glutinous foods like wheat and rye is the primary environmental factor. Several epigenetic mechanisms have been found to be implicated in Celiac disease. A high rate of DNA methylation of CpGs contributes to the development of small bowel adenocarcinomas, which are malignant tumors, in individuals with Celiac disease. Furthermore, unusual methylation in the genes involved in the core NF-κB pathway is implicated in the pathogenesis of Celiac disease. There are also allele-specific gene methylations that impact phenotype in such a way that it can lead to Celiac disease, thus involving allele-specific methylation in Celiac disease predisposition. Additionally, an increase in histone acetylation, specifically H3K27ac, has been found in Celiac disease biopsies.[14] Furthermore, the regulation of certain microRNAs, which are a type of non-coding RNA, differs significantly in individuals with Celiac disease compared to control individuals without Celiac disease. This significant difference was found to come in the form of downregulation of some microRNAs and upregulation of others.[15]
Addison's Disease
Addison's disease is a condition in which the immune system attacks the adrenal gland leading to an insufficiency in production of cortisol in response to stress which can be life threatening. Binding at glucocorticoid receptor (which bind cortisol) propagate epigenetic changes such as histone modification and DNA methylation of promoters and GC-response elements. [16] These alterations alter the sensitivity of these These polymorphisms Describe condition, discuss modifications described in these articles: [16], [3]
Graves' Disease
Graves’ disease is an autoimmune disease involving thyrotoxicosis, in which the body is affected by the overproduction of thyroid hormone, a quality termed hyperthyroidism. Like Hashimoto’s thyroiditis, Graves’ disease is qualified as an autoimmune thyroid disease. The epigenetic processes involved in Hashimoto’s thyroiditis, namely the modification of histone methylation in Tg and skewed X chromosome inactivation, are also involved in Graves’ disease. The viral infection possibility mentioned in reference to Hashimoto’s thyroiditis also applies to Graves’ disease.[6] In the specific case of Graves’ disease, discoveries have been made showing involvement of abnormal DNA methylation in certain CpG sites leading to interferon signaling and other immune system-related processes in cases of Graves’ disease. In fact, Graves’ disease patients have exhibited hypomethylation in CpG sites in certain T cells, indicating the implication of DNA hypomethylation in the pathophysiology of Graves’ disease.[17]
Systemic Sclerosis (SSc)
Systemic sclerosis is an autoimmune diseases that causes the patients skin and connective tissues to tighten and hardening, affecting the joints and various internal organ systems., hypermethylation of CpG islands in Fli1 promoter[5] Also discuss decreased levels of DNA methyltransferases (DNMTs) in CD4+ T cells[10]. Discuss modifications in these articles: [11], [3]
Sjogren's Syndrome
Describe condition, and how it is characterized by over expression of certain miRNAs in salivary glands[5]. Epigenetic aterations in CD4 and T-cells in the immune system are tied to this condition. Specifically, research has linked a decrease in expression of FOXP3 gene as well as CD70 promoter region hypomethylation to the development of Sjogren's syndrome. [3] Additionally, miRNA dysregulation is associated with this conditionand has been explored due to role that the innate immune system plays in this disease. miRNA-146a and miRNA-16a elevation are two key types of miRNA dysregulation tied to this disease [11]. Discuss modifications described in these articles: [11],[3]
Undifferentiated Connective Tissue Disorder
Describe condition, discuss how different epigenetic modifications are indicators of this condition differentiating into specific conditions such as SLE, RA, and where research is focused in this field. Having some challenging finding articles but want to try and keep looking. Possible resource: [18]
COMMENTS I was quite surprised to find out that there was not a Wikipedia article on this topic. Good job for finding this hole in the encyclopedia. You have a very broad and important topic that touches a great many things. For each one of subtopics you should search Wikipedia to see if a free standing article exists. If it does, you may want to give a mention the disease here with a very short description and then link to the more complete article for more information. Then in your article you would be free to shift your focus to just the relevant epigenetic information.
Thinking about this approach, I am sure that what you are going to find is that some of the articles that you might want to link to are poor quality. In that case you may find yourself editing another article. That is OK. You don't have to pour all of your words into this one document. Parts of your text that describes important aspects of the disease could be carved out and housed elsewhere.
I see that Trevor made a similar comment. Up to you how to handle it.
Is everyone in your group assigned a different subtopic? If so then you should each generate a quick first draft for your section -- even if it means that parts of the draft are still bullet points. After everyone this write a draft of their section trade and be each others' editors and critics. Read each others' drafts/outlines and meet to discuss how to organize the work (this will avoid redundancy such as everyone defining what HDACs are, but other more complex redundancies will also be avoided). Make real organizational suggestions to each other. Tell each other when prose cannot be easily understood. Be thick skinned when you get these comments.
You will be seeing this article in Wikipedia for a very long time to come. You want it to be great. It may evolve but it will still be yours.
Above all keep searching for new information. Sometimes new articles show up (Pubmed) when instead of searching for "Autoimmune Epigenetics" you search for "Autoimmune histone methylation" or some other combination of autoimmune and an enzyme or modification. A very large number of epigenetics papers manage to avoid the use of the word epigenetics. So as you learn terms and the names of enzymes add them to your search criteria.
I think that this article has the potential to be a highly viewed page in Wikipedia. I think that the start here is very good. Now is the time to flesh it out.
References
- ^ a b Brown, Chrysothemis C.; Wedderburn, Lucy R. (2015-03). "Mapping autoimmune disease epigenetics: what's on the horizon?". Nature Reviews Rheumatology. 11 (3): 131–132. doi:10.1038/nrrheum.2014.210. ISSN 1759-4790.
{{cite journal}}: Check date values in:|date=(help) - ^ a b c d e Long, Hai; Yin, Heng; Wang, Ling; Gershwin, M. Eric; Lu, Qianjin (2016-11). "The critical role of epigenetics in systemic lupus erythematosus and autoimmunity". Journal of Autoimmunity. 74: 118–138. doi:10.1016/j.jaut.2016.06.020.
{{cite journal}}: Check date values in:|date=(help) - ^ a b c d e Jokkel, Zsofia; Piroska, Marton; Szalontai, Laszlo; Hernyes, Anita; Tarnoki, David Laszlo; Tarnoki, Adam Domonkos (2021-01-01), Li, Shuai; Hopper, John L. (eds.), "Chapter 9 - Twin and family studies on epigenetics of autoimmune diseases", Twin and Family Studies of Epigenetics, Translational Epigenetics, vol. 27, Academic Press, pp. 169–191, doi:10.1016/b978-0-12-820951-6.00009-0, ISBN 978-0-12-820951-6, retrieved 2022-02-27
- ^ a b c Farh, Kyle Kai-How; Marson, Alexander; Zhu, Jiang; Kleinewietfeld, Markus; Housley, William J.; Beik, Samantha; Shoresh, Noam; Whitton, Holly; Ryan, Russell J. H.; Shishkin, Alexander A.; Hatan, Meital (2015-02-19). "Genetic and epigenetic fine mapping of causal autoimmune disease variants". Nature. 518 (7539): 337–343. doi:10.1038/nature13835. ISSN 0028-0836. PMC 4336207. PMID 25363779.
{{cite journal}}: CS1 maint: PMC format (link) - ^ a b c d e f g Quintero-Ronderos, Paula; Montoya-Ortiz, Gladis (2012). "Epigenetics and Autoimmune Diseases". Autoimmune Diseases. 2012: 1–16. doi:10.1155/2012/593720. ISSN 2090-0422. PMC 3318200. PMID 22536485.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ a b c d Tomer, Yaron (2014-01-24). "Mechanisms of Autoimmune Thyroid Diseases: From Genetics to Epigenetics". Annual Review of Pathology: Mechanisms of Disease. 9 (1): 147–156. doi:10.1146/annurev-pathol-012513-104713. ISSN 1553-4006. PMC 4128637. PMID 24460189.
{{cite journal}}: CS1 maint: PMC format (link) - ^ a b Le, Michelle; Muntyanu, Anastasiya; Netchiporouk, Elena (2020-03). "IncRNAs and circRNAs provide insight into discoid lupus pathogenesis and progression". Annals of Translational Medicine. 8 (6): 260–260. doi:10.21037/atm.2020.03.56. PMC 7186711. PMID 32355704.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ Küçükali, Cem İsmail; Kürtüncü, Murat; Çoban, Arzu; Çebi, Merve; Tüzün, Erdem (2015-06-01). "Epigenetics of Multiple Sclerosis: An Updated Review". NeuroMolecular Medicine. 17 (2): 83–96. doi:10.1007/s12017-014-8298-6. ISSN 1559-1174.
- ^ Elsen, Peter J. van den; Eggermond, Marja C. J. A. van; Puentes, Fabiola; Valk, Paul van der; Baker, David; Amor, Sandra (2014-03-01). "The epigenetics of multiple sclerosis and other related disorders". Multiple Sclerosis and Related Disorders. 3 (2): 163–175. doi:10.1016/j.msard.2013.08.007. ISSN 2211-0348. PMID 25878004.
- ^ a b c Wu, Haijing; Liao, Jieyue; Li, Qianwen; Yang, Ming; Zhao, Ming; Lu, Qianjin (2018-11). "Epigenetics as biomarkers in autoimmune diseases". Clinical Immunology. 196: 34–39. doi:10.1016/j.clim.2018.03.011.
{{cite journal}}: Check date values in:|date=(help) - ^ a b c d Ciechomska, Marzena; O’Reilly, Steven (2016-08-10). "Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases". Mediators of Inflammation. 2016: e9607946. doi:10.1155/2016/9607946. ISSN 0962-9351. PMC 4995328. PMID 27594771.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ Paul, Dirk S.; Teschendorff, Andrew E.; Dang, Mary A. N.; Lowe, Robert; Hawa, Mohammed I.; Ecker, Simone; Beyan, Huriya; Cunningham, Stephanie; Fouts, Alexandra R.; Ramelius, Anita; Burden, Frances (2016-11-29). "Increased DNA methylation variability in type 1 diabetes across three immune effector cell types". Nature Communications. 7 (1): 13555. doi:10.1038/ncomms13555. ISSN 2041-1723.
- ^ YIN, X.; LATIF, R.; TOMER, Y.; DAVIES, T. F. (2007-09-01). "Thyroid Epigenetics: X Chromosome Inactivation in Patients with Autoimmune Thyroid Disease". Annals of the New York Academy of Sciences. 1110 (1): 193–200. doi:10.1196/annals.1423.021. ISSN 0077-8923.
- ^ Gnodi, Elisa; Meneveri, Raffaella; Barisani, Donatella (2022-01-28). "Celiac disease: From genetics to epigenetics". World Journal of Gastroenterology. 28 (4): 449–463. doi:10.3748/wjg.v28.i4.449. ISSN 1007-9327. PMC 8790554. PMID 35125829.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ Dieli-Crimi, Romina; Cénit, M. Carmen; Núñez, Concepción (2015-11). "The genetics of celiac disease: A comprehensive review of clinical implications". Journal of Autoimmunity. 64: 26–41. doi:10.1016/j.jaut.2015.07.003.
{{cite journal}}: Check date values in:|date=(help) - ^ a b Motavalli, Roza; Majidi, Taraneh; Pourlak, Tala; Abediazar, Sima; Shoja, Mohammadali M.; Zununi Vahed, Sepideh; Etemadi, Jalal (2021-10). "The clinical significance of the glucocorticoid receptors: Genetics and epigenetics". The Journal of Steroid Biochemistry and Molecular Biology. 213: 105952. doi:10.1016/j.jsbmb.2021.105952.
{{cite journal}}: Check date values in:|date=(help) - ^ Razmara, Ehsan; Salehi, Mehrnaz; Aslani, Saeed; Bitaraf, Amirreza; Yousefi, Hassan; Colón, Jonathan Rosario; Mahmoudi, Mahdi (2021-02-01). "Graves' disease: introducing new genetic and epigenetic contributors". Journal of Molecular Endocrinology. 66 (2): R33 – R55. doi:10.1530/JME-20-0078. ISSN 1479-6813.
- ^ Alarcón, G. S.; Williams, G. V.; Singer, J. Z.; Steen, V. D.; Clegg, D. O.; Paulus, H. E.; Billingsley, L. M.; Luggen, M. E.; Polisson, R. P.; Willkens, R. F. (1991-09-01). "Early undifferentiated connective tissue disease. I. Early clinical manifestation in a large cohort of patients with undifferentiated connective tissue diseases compared with cohorts of well established connective tissue disease". The Journal of rheumatology. 18 (9): 1332–1339. ISSN 0315-162X. PMID 1757934.
- ^ Long, Hai; Yin, Heng; Wang, Ling; Gershwin, M. Eric; Lu, Qianjin (2016-11-01). "The critical role of epigenetics in systemic lupus erythematosus and autoimmunity". Journal of Autoimmunity. A Comprehensive perspective on systemic lupus erythematosus. 74: 118–138. doi:10.1016/j.jaut.2016.06.020. ISSN 0896-8411.