Cutting Edge: Chronic NF-κB Activation in CD4+ T Cells in Rheumatoid Arthritis Is Genetically Determined by HLA Risk Alleles

Spurlock, Charles F.; Tossberg, John T.; Olsen, Nancy J.; Aune, Thomas M.

doi:10.4049/jimmunol.1500267

Cited by 16 publications

(13 citation statements)

References 23 publications

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“…Other associations exist with genes that are in inflammatory pathways implicated in RA (e.g. CTLA4 (36), STAT4 (37), IL-6 (38), NF-kB (39)), and with genes related to enzymes that conceivably could participate in autoimmune responses, including the PAD enzymes that mediate citrullination (29, 36, 40). …”

Section: Genetic and Familial Risk Factors For Ramentioning

confidence: 99%

Genetic and environmental risk factors for rheumatoid arthritis

Deane

Demoruelle

Kelmenson

et al. 2017

Best Practice & Research Clinical Rheumatology

470

296

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Multiple genetic and environmental factors have been associated with an increased risk for rheumatoid arthritis (RA). Of these, the strongest associations have been seen with female sex, a family history of RA, the genetic factor the ‘shared epitope’ and with exposure to tobacco smoke. There is also renewed interest in mucosal inflammation and microbial factors as contributors to the development of RA. However, the identification of a ‘preclinical’ period of RA that can be defined as local or systemic autoimmunity as measured by autoantibodies and other biomarkers prior to the development of clinically-apparent synovitis suggests that the risk factors for RA are acting long prior to first clinical evidence of IA. As such, a major challenge to the field will be to investigate the full spectrum of the development of RA, from initiation and propagation of autoimmunity during preclinical RA and transition to clinically-apparent synovitis and classifiable RA, in order to determine which genetic and environmental factors are important at each stage of disease development. Understanding the exact role and timing of action of risk factors for RA is especially important given the advent of prevention trials in RA, and the hope that a full understanding of genetic and environmental factors in RA could lead to effective preventive interventions.

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Section: Genetic and Familial Risk Factors For Ramentioning

confidence: 99%

Genetic and environmental risk factors for rheumatoid arthritis

Deane

Demoruelle

Kelmenson

et al. 2017

Best Practice & Research Clinical Rheumatology

470

296

View full text Add to dashboard Cite

show abstract

“…11 The involvement of other genes that are implicated in inflammatory pathways and autoimmune responses, such as, signal transducer and activator of transcription 4 (STAT4), IL-2, IL-6 and NF-kB, have been confirmed by numerous studies. 73,77,87,88 An overview of RAassociated variants including their function and discovery method, prior to the development of GWAS, have been shown in Table 2.…”

Section: Genetic Factors That Contribute To Ra Pathogenesismentioning

confidence: 99%

The genetic pathogenesis, diagnosis and therapeutic insight of rheumatoid arthritis

Zamanpoor

2019

Clinical Genetics

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Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes chronic inflammation of the joints. RA is a heterogeneous disorder caused by an abnormal autoimmune response triggered by the complex interactions of genetic and environmental factors that contribute to RA etiology. However, its underlying pathogenic mechanisms are yet to be fully understood. In this review, I provide an overview of the pathogenesis, diagnosis and therapeutic insight in the clinical management of RA in light of the recent updates to classification criteria and recent discoveries of genetic loci associated with susceptibility for RA.

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“…As a result, NF-κB function impacts multiple cellular outcomes, including cell migration, proliferation, differentiation, and survival (77). While controlled NF-κB-mediated responses promote homeostasis, persistently elevated responses of this pathway are associated with diseases such as rheumatoid arthritis (RA) and OA (60,78). Despite the large body of evidence on the role of TAK1-IKK2-NF-κB axis in these diseases, the mechanisms by which pathologic activity of NF-κB induces joint catabolism are largely unknown.…”

Section: Homeostatic and Pathologic Nf-κb Signaling In The Skeletal Smentioning

confidence: 99%

Inflammation and epigenetic regulation in osteoarthritis

Shen

Abu‐Amer

O’Keefe

et al. 2016

Connective Tissue Research

194

140

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Osteoarthritis (OA) was once defined as a non-inflammatory arthropathy, but it is now well-recognized that there is a major inflammatory component to this disease. In addition to synovial cells, articular chondrocytes and other cells of diarthrodial joints are also known to express inflammatory mediators. It has been proposed that targeting inflammation pathways could be a promising strategy to treat OA. There have been many reports of cross-talk between inflammation and epigenetic factors in cartilage. Specifically, inflammatory mediators have been shown to regulate levels of enzymes that catalyze changes in DNA methylation and histone structure, as well as alter levels of non-coding RNAs. In addition, expression levels of a number of these epigenetic factors have been shown to be altered in OA, thereby suggesting potential interplay between inflammation and epigenetics in this disease. This review provides information on inflammatory pathways in arthritis and summarizes published research on how epigenetic regulators are affected by inflammation in chondrocytes. Furthermore, we discuss data showing how altered expression of some of these epigenetic factors can induce either catabolic or anti-catabolic effects in response to inflammatory signals. A better understanding of how inflammation affects epigenetic factors in OA may provide us with novel therapeutic strategies to treat this condition.

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Cutting Edge: Chronic NF-κB Activation in CD4+ T Cells in Rheumatoid Arthritis Is Genetically Determined by HLA Risk Alleles

Cited by 16 publications

References 23 publications

Genetic and environmental risk factors for rheumatoid arthritis

Genetic and environmental risk factors for rheumatoid arthritis

The genetic pathogenesis, diagnosis and therapeutic insight of rheumatoid arthritis

Inflammation and epigenetic regulation in osteoarthritis

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