Epigenetics of spondyloarthritis

Cherqaoui, Bilade; Crémazy, Frédéric; Hue, Christophe; Garchon, Henri‐Jean; Bréban, Maxime; Costantino, Félicie

doi:10.1016/j.jbspin.2020.06.003

Cited by 9 publications

(9 citation statements)

References 70 publications

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“…Genomic imprinting is a normal process that differentially regulates the expression of specific genes depending on the sex of the transmitting parent. Already more than twenty years ago, a higher penetrance of PsO was reported if the father was affected and a similar phenomenon was observed among PsA patients (Burden et al, 1998;Rahman et al, 1999;Karason et al, 2003). Later a significant linkage on chromosome 16q was noted only after conditioning for paternal transmission, suggesting that genetic imprinting may play a role in the inheritance pattern of psoriasis and PsA (Karason et al, 2003;Eder et al, 2012).…”

Section: Epigenetic Mechanisms In Spondyloarthritismentioning

confidence: 64%

“…In recent decades, the interest in epigenetic mechanisms increased due to the evidence that their alterations are present in many diseases, including autoimmune diseases. In SpA, alterations of histone H3 (H3K27ac and H3K4me1) seem to be correlated with RUNX3 expression and the decrease of CD8 + T cell in the presence of rs4648889 SNP variant ( Cherqaoui et al, 2020 ). In addition, H3K4me1 methylation regulates the activity of IL23R gene.…”

Section: Epigenetic Mechanisms In Spondyloarthritismentioning

confidence: 99%

“…These small molecules of non-coding RNAs can regulate the expression of multiple genes at a post-transcriptional level by inhibiting translation or inducing messenger RNA degradation. Significant alterations in miRNA expression have been observed in axSpA patients, showing a lower expression of 14 miRNAs in comparison with healthy controls ( Prajzlerová et al, 2017 ; Cherqaoui et al, 2020 ). Interestingly, most of these miRNAs are involved in osteoblast differentiation or the Wnt signaling pathway while only miR-625-3p was significantly different in nr-AxSpA patients compared to controls.…”

Section: Epigenetic Mechanisms In Spondyloarthritismentioning

confidence: 99%

“…DNA methyltransferase (DNMT) 3A and 3B are involved in genomic imprinting and X-chromosome inactivation, which may in part explain the different distribution of SpA according to gender ( Hanson and Brown, 2017 ; Hao et al, 2017 ). Variants in DNMT3A, DNMT3B, and DNMT3L genes have been recently associated with AS, and different methylated positions (DMPs), that can influence HLA-B27, are identified ( Ellinghaus et al, 2016 ; Cherqaoui et al, 2020 ). In addition, an increased level of Histone Deacetylase 3 (HDAC3), which regulates NF-kB activity, was detected in AS patients ( Jiang and Wang, 2016 ).…”

Section: Epigenetic Mechanisms In Spondyloarthritismentioning

confidence: 99%

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Genetics, Epigenetics, and Gender Impact in Axial-Spondyloarthritis Susceptibility: An Update on Genetic Polymorphisms and Their Sex Related Associations

et al. 2021

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Spondyloarthritis (SpA) is a group of chronic inflammatory rheumatic disease that can be divided into predominantly axial or predominantly peripheral involvement, with or without associated psoriasis, inflammatory bowel disease or previous infection. Axial SpA (axSpA) encompasses ankylosing spondylitis (AS) with radiological sacroiliitis, and a type without radiographic sacroiliitis, called “non-radiographic axial SpA” (nr-axSpA). Males and females show large differences in their susceptibility to SpA, such as distinctions in clinical patterns, phenotypes and in therapeutical response, particularly to TNF inhibitors (TNFi). Several studies indicate that AS women have doubled risk to failure TNFi compared with males. This diversity in drugs’ efficacy among women and men may be caused by differences in the balance of sex hormones and in gene-specific expression likely triggered by X-chromosome instability and gene-specific epigenetic modifications. Evidence reported that polymorphisms in microRNAs on X- and other chromosomes, such as miR-146a, miR-155, miR-125a-5p, miR-151a-3p and miR-22-3p, miR-199a-5p could be involved in the different clinical presentation of SpA, as well as disease activity. In addition, association with non−response to TNFi treatment and presence of IRAK3 and CHUCK genes in SpA patients was recently detected. Finally, polymorphisms in genes involved in IL-23/IL-17 pathway, such as in drug pharmacodynamics and pharmacokinetics may have a role in response to TNFi, IL17i, and IL23i. A major understanding of genomic variability could help in the development of new therapeutic targets or in taking advantages of different mechanisms of action of biological drugs. Moving from the multifactorial etiology of disease, the present review aims at evaluating genetic and epigenetic factors and their relationship with sex and bDMARDs response, helping to investigate the different expression among males and females of genes on X- and other chromosomes, as well as mi-RNA, to highlight relationships between sex and occurrence of specific phenotypes and symptoms of the disease. Moreover, the role of the epigenetic modification in relation to immune-regulatory mechanisms will be evaluated.

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Section: Epigenetic Mechanisms In Spondyloarthritismentioning

confidence: 64%

Section: Epigenetic Mechanisms In Spondyloarthritismentioning

confidence: 99%

Section: Epigenetic Mechanisms In Spondyloarthritismentioning

confidence: 99%

Section: Epigenetic Mechanisms In Spondyloarthritismentioning

confidence: 99%

See 2 more Smart Citations

Genetics, Epigenetics, and Gender Impact in Axial-Spondyloarthritis Susceptibility: An Update on Genetic Polymorphisms and Their Sex Related Associations

et al. 2021

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“…The balance between histone acetyltransferases and histone deacetylases determines the overall level of acetylated histones in cells 39 . The study found a significant increase of HAT/HDAC ratio in patients with AS treated with tumor necrosis factor (TNF) inhibitors.…”

Section: Histone Modification and Asmentioning

confidence: 91%

Epigenetics of ankylosing spondylitis: Recent developments

Yang

Chen

et al. 2021

Int J of Rheum Dis

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Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease which mainly affects the spine, sacroiliac joint and peripheral joints. To date, the exact causes and pathogenesis of AS still remain unknown. It is considered that the pathogenesis of AS is associated with genetic, infection, environment, immunity and other factors. Among them, the role of genetic factors in the pathogenesis of AS has been studied most deeply. However, over the past few years, the function of environmental predisposition and epigenetic modification in the pathogenesis of AS has received extensive attention. This paper summarizes the recent progress in the epigenetics of AS, including abnormal epigenetic modifications at AS‐associated genomic loci, such as DNA methylation, histone modification, microRNA, and so on. In summary, the findings of this review attempt to explain the role of epigenetic modification in the occurrence and development of AS. Nevertheless, there are still unknown and complicated aspects worth exploring to deepen our understanding of the pathogenesis of AS.

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How Has Molecular Biology Enhanced Our Undertaking of axSpA and Its Management

et al. 2022

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Purpose This review aims at investigating pathophysiological mechanisms in spondyloarthritis (SpA). Analysis of genetic factors, immunological pathways, and abnormalities of bone metabolism lay the foundations for a better understanding of development of the axial clinical manifestations in patients, allowing physician to choose the most appropriate therapeutic strategy in a more targeted manner. Recent Findings In addition to the contribution of MHC system, findings emerged about the role of non-HLA genes (as ERAP1 and 2, whose inhibition could represent a new therapeutic approach) and of epigenetic mechanisms that regulate the expression of genes involved in SpA pathogenesis. Increasing evidence of bone metabolism abnormalities secondary to the activation of immunological pathways suggests the development of various bone anomalies that are present in axSpA patients. Summary SpA are a group of inflammatory diseases with a multifactorial origin, whose pathogenesis is linked to the genetic predisposition, the action of environmental risk factors, and the activation of immune response. It is now well known how bone metabolism leads to long-term structural damage via increased bone turnover, bone loss and osteoporosis, osteitis, erosions, osteosclerosis, and osteoproliferation. These effects can exist in the same patient over time or even simultaneously. Evidence suggests a cross relationship among innate immunity, autoimmunity, and bone remodeling in SpA, making treatment approach a challenge for rheumatologists. Specifically, treatment targets are consistently increasing as new drugs are upcoming. Both biological and targeted synthetic drugs are promising in terms of their efficacy and safety profile in patients affected by SpA.

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Epigenetics of spondyloarthritis

Cited by 9 publications

References 70 publications

Genetics, Epigenetics, and Gender Impact in Axial-Spondyloarthritis Susceptibility: An Update on Genetic Polymorphisms and Their Sex Related Associations

Genetics, Epigenetics, and Gender Impact in Axial-Spondyloarthritis Susceptibility: An Update on Genetic Polymorphisms and Their Sex Related Associations

Epigenetics of ankylosing spondylitis: Recent developments

How Has Molecular Biology Enhanced Our Undertaking of axSpA and Its Management

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