Abstract:
:With unknown etiology, scleroderma (SSc) is a multifaceted disease characterized by immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while genetic susceptibility to SSc appears to be modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated. The non-HLA genes associated with SSc are involved in various functions, with the most robust associations including genes for B and T cell activation and innate immunity. Other pathways include genes involved in extracellular matrix deposition, cytokines, and autophagy. Among these genes, IRF5, STAT4, and CD247 were replicated most frequently while SNPs rs35677470 in DNASE1L3, rs5029939 in TNFAIP3, and rs7574685 in STAT4 have the strongest associations with SSc. In addition to genetic predisposition, it became clear that environmental factors and epigenetic influences also contribute to the development of SSc. Epigenetics, which refers to studies that focus on heritable phenotypes resulting from changes in chromatin structure without affecting the DNA sequence, is one of the most rapidly expanding fields in biomedical research. Indeed extensive epigenetic changes have been described in SSc. Alteration in enzymes and mediators involved in DNA methylation and histone modification, as well as dysregulated non-coding RNA levels all contribute to fibrosis, immune dysregulation, and impaired angiogenesis in this disease. Genes that are affected by epigenetic dysregulation include ones involved in autoimmunity, T cell function and regulation, TGFβ pathway, Wnt pathway, extracellular matrix, and transcription factors governing fibrosis and angiogenesis. In this review, we provide a comprehensive overview of the current findings of SSc genetic susceptibility, followed by an extensive description and a systematic review of epigenetic research that has been carried out to date in SSc. We also summarize the therapeutic potential of drugs that affect epigenetic mechanisms, and outline the future prospective of genomics and epigenomics research in SSc.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Tsou PS,Sawalha AHdoi
10.1016/j.jaut.2017.05.004subject
Has Abstractpub_date
2017-09-01 00:00:00pages
73-94eissn
0896-8411issn
1095-9157pii
S0896-8411(17)30325-6journal_volume
83pub_type
杂志文章,评审abstract::Interferon regulatory factor-1 (IRF-1), a transcriptional factor, regulates type I interferon and interferon-induced genes. It was reported that IRF-1 regulates important molecules required for inflammation and immune reactions. To investigate the role of IRF-1 in the development of autoimmune diabetes, we established...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2001.0531
更新日期:2001-09-01 00:00:00
abstract::To explore the mechanisms underlying liver-directed autoimmune reactions in acute Hepatitis B Virus (HBV) infection, we followed five subjects who were identified in the early incubation phase (30-70 days before the first elevation of transaminases). We assessed serially cellular (using a T-lymphocyte migration inhibi...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(88)90034-0
更新日期:1988-06-01 00:00:00
abstract::Our aim was to investigate presence of tumour necrosis factor (TNF) and interleukin (IL)-10 in serum and their relation to different genotypes as well as to clinical and laboratory phenotypes in patients with polymyositis and dermatomyositis. In 65 patients with poly- or dermatomyositis the inflammatory cytokine balan...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2006.06.003
更新日期:2006-08-01 00:00:00
abstract::A major concept in autoimmunity is that disruption of Foxp3(+) regulatory T cells (Tregs) predisposes to breach of tolerance. This is exemplified by the Foxp3-linked disorder termed IPEX (immunodysregulation, polyendocrinopathy, enteropathy, X-linked) which affects newborn children. There has been considerable clinica...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2013.08.010
更新日期:2014-05-01 00:00:00
abstract::Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by necrotizing vasculitis with the presence of pathogenic ANCA. ANCA can potentially cause neutrophil activation and induce neutrophil extracellular traps (NETs), resulting in endothelial damage as well as activation of autoreacti...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.102390
更新日期:2020-03-01 00:00:00
abstract::Despite a broad clinical spectrum, paraneoplastic enecephalomyelitis/sensory neuronopathy (PEM/SSN) is characterized by the presence of a common autoantibody, referred to as anti-Hu or type I anti-neuronal nuclear antibody (ANNA-1). The target of these antibodies is a family of four Hu antigens: three (Hel-N1, HuC, Hu...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1999.0337
更新日期:1999-12-01 00:00:00
abstract::Genetic abnormalities predisposing to autoimmunity generally act in a cooperative manner affecting one or several mechanisms regulating immunological tolerance. In addition, many of these genetic abnormalities are also involved in the development of lymphoproliferative diseases. In the present study, we have determine...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2010.07.002
更新日期:2010-12-01 00:00:00
abstract::Dysregulation of autophagy has been implicated in the development of various disease indications including autoimmune diseases. Here we identified hitherto unsuspected molecular alterations of autophagy occurring at an early stage of the macroautophagy pathway in the salivary glands and spleen of NOD.H-2h4 mice that d...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2020.102418
更新日期:2020-03-01 00:00:00
abstract::Various specific and non-specific environmental factors have been associated with the induction and/or exacerbation of disease activity in patients with Crohn's disease and ulcerative colitis. One such factor is the potential role of ingested ultrafine particles. In fact, based on a Western diet, recent data suggest t...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1999.0342
更新日期:2000-02-01 00:00:00
abstract::A large number of autoimmune diseases (ADs) are more prevalent in women. The more frequent the AD and the later it appears, the more women are affected. Many ideas mainly based on hormonal and genetic factors that influence the autoimmune systems of females and males differently, have been proposed to explain this pre...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2011.10.003
更新日期:2012-05-01 00:00:00
abstract::The antigenic specificity of anti-phospholipid antibodies (APA) is a matter of intensive investigation. To further characterize these antibodies, we attempted to isolate human monoclonal APA. B-cells of patients with at least one positive test for antibodies against cardiolipin, phosphatidylserine, beta2-glycoprotein ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1999.0316
更新日期:1999-09-01 00:00:00
abstract::HLA-DQB1 is widely considered to be the major histocompatibility complex (MHC) susceptibility gene for type 1 diabetes (T1D). However, since inheritance of the gene in T1D is recessive, the presence of the protective HLA-DQB1 0602 allele with normal nucleotide sequence in some patients raises the question of whether H...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2007.10.006
更新日期:2008-06-01 00:00:00
abstract::Autoimmune diseases (AIDs) are believed to be multifactorial diseases that commonly involve multiple organ systems. About three fourth of the patients afflicted with AIDs are women suggesting that sex differences impact the incidence of AID. However, the proportion of females to males suffering from AID varies dependi...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2011.12.001
更新日期:2012-05-01 00:00:00
abstract::Murine monoclonal antibodies (mAb) reacting with affinity-purified antihistone antibodies (AHA) from serum of a patient with systemic lupus erythematosus (SLE) were obtained. One of them, 8B3, was initially considered to recognize idiotypic (Id) determinants in AHA since (a) it reacted with AHA but not with control Ig...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(92)90149-k
更新日期:1992-06-01 00:00:00
abstract::Peptidyl arginine deiminases (PADs) catalyze a post-translational protein modification reaction called citrullination, where arginine is converted to citrulline. This modification has been linked to the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA). More recently, several studies have suggest...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2012.03.004
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND/PURPOSE:Primary Sjögren's syndrome (SS) is a chronic autoimmune disease primarily involving the exocrine glands. The clinical picture of SS ranges from exocrinopathy to systemic disease affecting the lung, kidney, liver, skin, musculockeletal and nervous systems. The morbidity of SS is mainly determined by e...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2012.05.018
更新日期:2012-09-01 00:00:00
abstract::University of California at Davis line 200 (UCD-200) chickens develop a hereditary connective tissue disease characterized by severe lymphocytic infiltration, vascular occlusion and fibrosis of skin and internal organs. To identify cellular immunological abnormalities in the acute inflammatory disease stage of this an...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(91)90178-f
更新日期:1991-08-01 00:00:00
abstract::Autoinflammatory diseases (AUIDs) are a genetically heterogeneous group of rheumatic diseases characterized by episodic inflammation linked with dysregulated innate immune responses. In this review, we summarize the molecular mechanisms altered by disease-associated variants in several AUIDs, including NOD2-associated...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2017.10.012
更新日期:2018-03-01 00:00:00
abstract::The La antigen is a highly conserved protein, originally defined by sera of patients with Sjögren's syndrome or systemic lupus erythematosus (SLE). In the present study, we have produced and characterized a monoclonal anti-la antibody derived from mice with experimental SLE. The induction of SLE in these mice was achi...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(05)80037-x
更新日期:1990-12-01 00:00:00
abstract::Increasing evidence suggests that immune complexes made of anti-nuclear antibodies bound to nucleosomes released from dead cells play an important role in the pathogenesis of lupus nephritis. However, the nature and composition of apoptotic nucleosomes still remain elusive. Since large amounts of nucleosomes are relea...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1997.0172
更新日期:1998-02-01 00:00:00
abstract::We investigated the in vivo pathogenic potential of murine autoimmunity to peptides of the glutamate/AMPA receptor subunit 3 (GluR3). Antibodies to GluR3 are found in human epilepsy, Rasmussen's encephalitis (RE). In our accompanying paper in this issue we found that murine antibodies to the GluR3B peptide (amino acid...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1999.0297
更新日期:1999-08-01 00:00:00
abstract::There are two classes of autoimmune disease, organ-specific and non-organ specific or systemic. That cells producing autoantibodies are selected by antigen is strongly suggested by the presence of mutations and high affinity antibody. T-cells are pivotal in all forms of autoimmunity as evidenced by the therapeutic ben...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/0896-8411(92)90015-i
更新日期:1992-04-01 00:00:00
abstract::A dual isotype (IgG, IgA) enzyme-linked immunosorbent assay (ELISA) designed to provide enhanced detection of primary biliary cirrhosis (PBC)-specific autoantibodies against both major mitochondrial and nuclear antigens has been developed and recently become commercially available. The assay (PBC Screen) simultaneousl...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2010.09.005
更新日期:2010-12-01 00:00:00
abstract::IL-10 has been shown to be an important anti-inflammatory mediator that has both down-regulatory and immunomodulatory effects. Utilizing IL-10(-/-) mice we demonstrate the induction of low dose oral tolerance characterized by the up-regulation of TGF-beta and IL-4 and the suppression of Ag specific proliferation with ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2004.08.001
更新日期:2004-11-01 00:00:00
abstract::Systemic lupus erythematosus (SLE) is a prototype autoimmune disease characterized by various immunological abnormalities, including dysregulated activation of T and B lymphocytes, which trigger autoantibody production and immune-complex deposition. E4BP4, also known as NFIL3, has emerged as a major transcription fact...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2013.01.004
更新日期:2013-03-01 00:00:00
abstract::Sjögren's syndrome (SS) is a chronic autoimmune disorder that is characterized by dysfunction and destruction of the exocrine glands. Exocrinopathy is associated with periductal mononuclear cell infiltrates in the affected exocrine glands and B-cell hyperreactivity. Epithelial cells are thought to play an important pa...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2010.06.011
更新日期:2010-11-01 00:00:00
abstract::Women with antiphospholipid antibodies (aPL) are at high risk for pregnancy complications, such as preeclampsia. We previously demonstrated that aPL recognizing β2GPI promote an extravillous trophoblast pro-inflammatory, anti-migratory and anti-angiogenic profile similar to that seen in preeclampsia. Since preeclampsi...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2018.12.003
更新日期:2019-03-01 00:00:00
abstract:OBJECTIVES:To determine prevalence and co-existence of myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs) and associated clinical characteristics in a large cohort of idiopathic inflammatory myopathy (IIM) patients. METHODS:Adult patients with confirmed IIM recruited to the EuroMyosi...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.04.001
更新日期:2019-07-01 00:00:00
abstract::Sjögren's syndrome (SS) is an autoimmune rheumatic disease that targets salivary and lachrymal glands, characterized by a high concentration of serum autoantibodies directed against nuclear and cytoplasmic antigens. It is known that autoantibodies can enter viable cells and this phenomenon has functional consequences ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2006.05.001
更新日期:2006-08-01 00:00:00
abstract::Oxidative stress makes an important contribution to the development of autoimmune diabetes. We therefore tested the possible therapeutic value of two anti-oxidants, butylated hydroxyanisole (BHA) and pyrrolidine dithiocarbamate (PDTC), in the animal model of diabetes induced in susceptible DA rats by multiple low dose...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2004.01.005
更新日期:2004-06-01 00:00:00