Tuesday, June 11, 2019 4:02:38 AM
Rett Syndrome is an epigenetic disease. Success in treating RS would indicate that there is hope for autoimmune disorders.
The emerging role of epigenetics in human autoimmune disorders
Roberta Mazzone, Clemens Zwergel, Marco Artico, Samanta Taurone, Massimo Ralli, Antonio Greco and Antonello MaiEmail authorView ORCID ID profile
Clinical Epigenetics201911:34
https://doi.org/10.1186/s13148-019-0632-2©; The Author(s). 2019
Received: 23 December 2018Accepted: 12 February 2019Published: 26 February 2019
Abstract
Epigenetic pathways play a pivotal role in the development and function of the immune system. Over the last decade, a growing body of studies has been published out seeking to explain a correlation between epigenetic modifications and the development of autoimmune disorders. Epigenetic changes, such as DNA methylation, histone modifications, and noncoding RNAs, are involved in the pathogenesis of autoimmune diseases mainly by regulating gene expression. This paper reviews the importance of epigenetic alterations during the development of the most prevalent human autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), Sjogren’s syndrome (SS), autoimmune thyroid diseases (AITD), and type 1 diabetes (T1D), aiming to provide new insights in the pathogenesis of autoimmune diseases and the possibility to develop novel therapeutic approaches targeting the epigenome.
Background
Epigenetic mechanisms, known for their ability to regulate gene transcription and genomic stability, are key players for maintaining normal cell growth, development, and differentiation [1]. The term “epigenetics” can be outlined as the meiotically/mitotically heritable alterations in gene expression, related to environmental factors, without changes to the sequence of bases in the DNA [1]. Since genome-wide profiling in some cases does not give a sufficient answer to explain the complex biological processes in autoimmune disorders, epigenetic modifications are retained additional regulators in immune responses (Fig. 1). Epigenetic dysregulation directly influences the development of autoimmunity by regulating immune cell functions [2]. The recognition of the complexity of the interaction between epigenetic events and the alteration of the immune system in autoimmune disorders is a prominent challenge for the discovery of novel potential therapeutic strategies. Epigenetic mechanisms, such as DNA methylation, chromatin remodeling, and noncoding RNAs, have been identified as crucial regulators in cellular immunity, owing to their mechanisms in modulating gene expression and transcription in targeted cells and tissues [3]. Extensive evidences indicate that autoimmune diseases are mainly an interplay of genetic and non-genetic factors, although the role of the latter ones often remains unclear. Over the last decade, the influence of epigenetic modifications on innate and adaptive immunity has been intensively investigated, especially in autoimmune disorders.
Material ommitted please see the link. The list below is from a table in the article
Most relevant autoimmune diseases with known autoantigen targets
Systemic autoimmune diseases
Disease
Organ
Autoantigens
Mechanism of damage
Worldwide prevalence (%)
Ref.
Rheumatoid arthritis
Joints, lung, heart, etc.
IgG, filaggrin, fibrin etc.
T cell in joint/antibody
0.8
[33, 34, 35, 72, 73, 74]
Systemic lupus
Skin, joints, kidneys, brain, lungs, heart, others
Nuclear antigens (DNA, histones, ribonucleoproteins), others
Antibody
0.1
[33, 34, 35, 49, 50]
Polymyositis/dermatomyositis
Skeletal muscle (predominant), lungs, heart, joints, others
Muscle antigens, aminoacyl-tRNA synthetases, other nuclear antigens
T cell/antibody
<?0.01
[33, 34, 35, 36, 95]
Systemic sclerosis
Lungs, river, kidneys, heart, skin, etc.
Dermal fibroblast antigens, fibrillarin-1, metalloproteinases, etc.
Antibody
0.3
[33, 34, 35, 94, 95]
Sjogren’s syndrome
Connective tissue, salivary gland, lungs, bowel, etc.
Nuclear antigens, carbonic anhydrase I (CA-I), profiling
T cell/Antibody
0.1–0.6
[33, 34, 35, 115, 116]
Organ-specific autoimmune diseases
Disease
Organ
Autoantigens
Mechanism of damage
Prevalence (%)
Ref.
Thyroiditis (autoimmune)
Thyroid
Thyroglobulin, thyroid peroxidase
T cell/antibody
1.0–2.0
[33, 35, 130, 131, 132, 133, 134]
Gastritis
Stomach
H+/K+ ATPase, intrinsic factor
T cell/antibody
1–2 in >?60?years old
[33, 35]
Celiac disease
Small bowel
Transglutaminase
T cell/antibody
0.2–1.1
[33, 35]
Graves’ disease
Thyroid
Thyroid-stimulating hormone receptor
Antibody
0.2–1.1
[33, 35, 130, 131]
Vitiligo
Melanocytes
Tyrosinase, tyrosinase-related protein-2
T cell/antibody
0.4
[33, 35]
Type 1 diabetes
Pancreas ß cells
Insulin, glutamic acid decarboxylase
T cell
0.2–0.4
[33, 35, 149, 150, 151, 152]
Multiple sclerosis
Brain, spinal cord
Myelin basic protein, proteolipid protein
T cell
0.01–0.15
[33, 35]
Hepatitis (autoimmune)
Liver
Hepatocyte antigens (cytochrome P450)
T cell/antibody
<?0.01
[33, 35]
Myasthenia gravis
Muscle
Acetylcholine receptor
Antibody
<?0.01
[33, 35]
Primary biliary cirrhosis
Liver bile ducts
2-oxoacid dehydrogenase complexes
T cell/antibody
<?0.01
[33, 35]
Pemphigus
Skin
Desmogleins
Antibody
<?0.01–>?3.0
[33, 35]
S
https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-019-0632-2
In Peace, In War
