3? polymorphisms of ETS1 are associated with different clinical phenotypes in SLE

Sullivan, Kathleen E.; Piliero, Lisa M.; Dharia, Tushar; Goldman, Daniel; Petri, Michelle

doi:10.1002/1098-1004(200007)16:1<49::aid-humu9>3.0.co;2-z

Cited by 30 publications

(7 citation statements)

References 24 publications

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“…Human data implicating IL-17 in lupus has become available [82, 94]. In contrast, some evidence argues against a role for IL-17 in human lupus [45, 61] (Table 1).…”

Section: Are Th17 Cells Found In Different Arthropathies?mentioning

confidence: 99%

Th17 cytokines and arthritis

2010

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Th17 cells are implicated in human autoimmune diseases, such as rheumatoid arthritis (RA), although it has not been established whether this persistent destructive arthritis is driven by Th1 and/or Th17 cells. Interleukin-17A (IL-17A) contributes to the pathogenesis of arthritis as has been shown in several experimental arthritis models. Importantly, recent data from first clinical trials with anti-IL-17A antibody treatment in psoriatic arthritis patients and RA patients looks promising. This review summarizes the findings about the role of Th17 cells in arthritis and discusses the impact of the different Th17 cytokines in the pathogenesis of this disease. However, further studies are needed to unravel the interplay between IL-17A and other Th17 cytokines such as IL-17F, IL-22, and IL-21 in the pathoimmunological process of this crippling disease, in particular, whether regulating Th17 cell activity or specific combinations of Th17 cytokines will have additional value compared to neutralizing IL-17A activity alone. Moreover, tumor necrosis factor-positive Th17 cells are discussed as potential dangerous cells in driving persistent arthritis in human early RA.

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“…Human data implicating IL-17 in lupus has become available [82, 94]. In contrast, some evidence argues against a role for IL-17 in human lupus [45, 61] (Table 1).…”

Section: Are Th17 Cells Found In Different Arthropathies?mentioning

confidence: 99%

Th17 cytokines and arthritis

2010

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“…The patient bearing the novel variant in the ETS1 locus was diagnosed at age 12. Over an 8-year observation period, the patient experienced arthritis, haematuria and lymphopenia, but had not (yet) displayed anti-cardiolipin antibodies, discoid lesions, vasculitis or thrombocytopenia, disease manifestations that had previously been associated with various ETS1 alleles in SLE patients 42 .…”

Section: Resultsmentioning

confidence: 99%

Rare variants in non-coding regulatory regions of the genome that affect gene expression in systemic lupus erythematosus

Jones

Cantsilieris

Fan

et al. 2019

Sci Rep

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Personalized medicine approaches are increasingly sought for diseases with a heritable component. Systemic lupus erythematosus (SLE) is the prototypic autoimmune disease resulting from loss of immunologic tolerance, but the genetic basis of SLE remains incompletely understood. Genome wide association studies (GWAS) identify regions associated with disease, based on common single nucleotide polymorphisms (SNPs) within them, but these SNPs may simply be markers in linkage disequilibrium with other, causative mutations. Here we use an hierarchical screening approach for prediction and testing of true functional variants within regions identified in GWAS; this involved bioinformatic identification of putative regulatory elements within close proximity to SLE SNPs, screening those regions for potentially causative mutations by high resolution melt analysis, and functional validation using reporter assays. Using this approach, we screened 15 SLE associated loci in 143 SLE patients, identifying 7 new variants including 5 SNPs and 2 insertions. Reporter assays revealed that the 5 SNPs were functional, altering enhancer activity. One novel variant was linked to the relatively well characterized rs9888739 SNP at the ITGAM locus, and may explain some of the SLE heritability at this site. Our study demonstrates that non-coding regulatory elements can contain private sequence variants affecting gene expression, which may explain part of the heritability of SLE.

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“…By 2016 there were a large number of studies that linked polymorphisms in the human ETS1 gene with susceptibility to lupus (Bentham et al, 2015;Han et al, 2009;He et al, 2010;Leng et al, 2012;Lessard et al, 2016;Lu et al, 2015;Molineros et al, 2014;Morris et al, 2016;Sullivan et al, 2000;Wang et al, 2013;Yang et al, 2010;Zhang et al, 2013; F I G U R E 1 Summary of known roles for Ets1 in regulating B and T cell function. Ets1 is highly expressed in naïve quiescent B and T cells, but is downregulated upon activation.…”

Section: Systemic Lupus Erythematosus (Lupus)mentioning

confidence: 99%

“…Another SNP, rs1128334, is in the 3 0 UTR of Ets1 and regulates mRNA abundance in PBMCs (Yang et al, 2010). Some SNPs are also linked with the occurrence of particular lupus clinical manifestations including age, skin rashes, arthritis, vasculitis, or renal involvement (He et al, 2010;Sullivan et al, 2000;Zhong et al, 2011). More recently, several additional pieces of data have added to the linkage of Ets1 to lupus.…”

Section: B Cell Roles Of Ets1 Described In Vivo In Micementioning

confidence: 99%

An update on the roles of transcription factor Ets1 in autoimmune diseases

Garrett‐Sinha

2023

WIREs Mechanisms of Disease

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Transcription factors are crucial to regulate gene expression in immune cells and in other cell types. In lymphocytes, there are a large number of different transcription factors that are known to contribute to cell differentiation and the balance between quiescence and activation. One such transcription factor is E26 oncogene homolog 1 (Ets1). Ets1 expression is high in quiescent B and T lymphocytes and its levels are decreased upon activation. The human ETS1 gene has been identified as a susceptibility locus for many autoimmune and inflammatory diseases. In accord with this, gene knockout of Ets1 in mice leads to development of a lupus‐like autoimmune disease, with enhanced activation and differentiation of both B cells and T cells. Prior reviews have summarized functional roles for Ets1 based on studies of Ets1 knockout mice. In recent years, numerous additional studies have been published that further validate ETS1 as a susceptibility locus for human diseases where immune dysregulation plays a causative role. In this update, new information that further links Ets1 to human autoimmune diseases is organized and collated to serve as a resource. This update also describes recent studies that seek to understand molecularly how Ets1 regulates immune cell activation, either using human cells and tissues or mouse models. This resource is expected to be useful to investigators seeking to understand how Ets1 may regulate the human immune response, particularly in terms of its roles in autoimmunity and inflammation.This article is categorized under: Immune System Diseases > Genetics/Genomics/Epigenetics Immune System Diseases > Molecular and Cellular Physiology

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3? polymorphisms of ETS1 are associated with different clinical phenotypes in SLE

Cited by 30 publications

References 24 publications

Th17 cytokines and arthritis

Th17 cytokines and arthritis

Rare variants in non-coding regulatory regions of the genome that affect gene expression in systemic lupus erythematosus

An update on the roles of transcription factor Ets1 in autoimmune diseases

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