A genetic study on C5-TRAF1 and progression of joint damage in rheumatoid arthritis

Steenbergen, H.W. van; Rodríguez‐Rodríguez, Luis; Berglin, Ewa; Zhernakova, Alexandra; Knevel, Rachel; Ivorra-Cortés, José; Huizinga, Tom W J; Fernández‐Gutiérrez, Benjamín; Gregersen, Peter K.; Rantapää-Dahlqvist, Solbritt; Mil, Annette H M van der Helm-van

doi:10.1186/s13075-014-0514-0

Cited by 133 publications

(111 citation statements)

References 39 publications

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“…Other serum markers for eOA detection have been suggested - disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, matrix metalloproteinase (MMP)-1 and MMP-3 - but sensitivity and specificity was not reported [54]. The diagnostic performance of the two-step algorithm herein improves significantly on other current candidate biomarkers proposed for early-stage arthritis [16, 55, 56]. …”

Section: Discussionmentioning

confidence: 94%

Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoarthritis of the knee and typing and progression of arthritic disease

et al. 2016

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BackgroundThere is currently no blood-based test for detection of early-stage osteoarthritis (OA) and the anti-cyclic citrullinated peptide (CCP) antibody test for rheumatoid arthritis (RA) has relatively low sensitivity for early-stage disease. Morbidity in arthritis could be markedly decreased if early-stage arthritis could be routinely detected and classified by clinical chemistry test. We hypothesised that damage to proteins of the joint by oxidation, nitration and glycation, and with signatures released in plasma as oxidized, nitrated and glycated amino acids may facilitate early-stage diagnosis and typing of arthritis.MethodsPatients with knee joint early-stage and advanced OA and RA or other inflammatory joint disease (non-RA) and healthy subjects with good skeletal health were recruited for the study (n = 225). Plasma/serum and synovial fluid was analysed for oxidized, nitrated and glycated proteins and amino acids by quantitative liquid chromatography-tandem mass spectrometry. Data-driven machine learning methods were employed to explore diagnostic utility of the measurements for detection and classifying early-stage OA and RA, non-RA and good skeletal health with training set and independent test set cohorts.ResultsGlycated, oxidized and nitrated proteins and amino acids were detected in synovial fluid and plasma of arthritic patients with characteristic patterns found in early and advanced OA and RA, and non-RA, with respect to healthy controls. In early-stage disease, two algorithms for consecutive use in diagnosis were developed: (1) disease versus healthy control, and (2) classification as OA, RA and non-RA. The algorithms featured 10 damaged amino acids in plasma, hydroxyproline and anti-CCP antibody status. Sensitivities/specificities were: (1) good skeletal health, 0.92/0.91; (2) early-stage OA, 0.92/0.90; early-stage RA, 0.80/0.78; and non-RA, 0.70/0.65 (training set). These were confirmed in independent test set validation. Damaged amino acids increased further in severe and advanced OA and RA.ConclusionsOxidized, nitrated and glycated amino acids combined with hydroxyproline and anti-CCP antibody status provided a plasma-based biochemical test of relatively high sensitivity and specificity for early-stage diagnosis and typing of arthritic disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1154-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 94%

Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoarthritis of the knee and typing and progression of arthritic disease

et al. 2016

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“…Specifically, it was recently shown that in models of the inflammatory disease of osteoarthritis, HDAC inhibition (HDACi) reduced symptoms by directly increasing acetylation of Nrf2 and histone H3 [63]. These changes occurred in parallel with a decrease in inflammatory markers such as IL-6 and TNFα, potentially via direct transcriptional regulation.…”

Section: Epigenetics and Redox Dependent Metabolic Regulationmentioning

confidence: 99%

Redox biology and the interface between bioenergetics, autophagy and circadian control of metabolism

Wende

Young

Chatham

et al. 2016

Free Radical Biology and Medicine

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Understanding molecular mechanisms that underlie the recent emergence of metabolic diseases such as diabetes and heart failure has revealed the need for a multi-disciplinary research integrating the key metabolic pathways which change the susceptibility to environmental or pathologic stress. At the physiological level these include the circadian control of metabolism which aligns metabolism with temporal demand. The mitochondria play an important role in integrating the redox signals and metabolic flux in response to the changing activities associated with chronobiology, exercise and diet. At the molecular level this involves dynamic post-translational modifications regulating transcription, metabolism and autophagy. In this review we will discuss different examples of mechanisms which link these processes together. An important pathway capable of linking signaling to metabolism is the post-translational modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc). This is a nutrient regulated protein modification that plays an important role in impaired cellular stress responses. Circadian clocks have also emerged as critical regulators of numerous cardiometabolic processes, including glucose/lipid homeostasis, hormone secretion, redox status and cardiovascular function. Central to these pathways are the response of autophagy, bioenergetics to oxidative stress, regulated by Keap1/Nrf2 and mechanisms of metabolic control. The extension of these ideas to the emerging concept of bioenergetic health will be discussed.

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“…Researchers have identified a number of risk factors for the worsening of knee OA symptoms and structure, such as age, ethnicity and malalignment 3, 4 , however modifiable risk factors are required to prevent progression to advanced disease and/or surgery. To date, the strongest known modifiable risk factors for worsening of knee pain in people with knee OA are a higher body mass index (BMI) and infrapatellar fat pad or intercondylar synovitis 4 , whilst a recent meta-analysis identified greater knee pain at baseline as the only modifiable risk factor associated with structural progression 3 .…”

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confidence: 99%

Longitudinal association between foot and ankle symptoms and worsening of symptomatic radiographic knee osteoarthritis: data from the osteoarthritis initiative

Paterson

Kasza

Hunter

et al. 2017

Osteoarthritis and Cartilage

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Objective To assess whether foot and/or ankle symptoms are associated with an increased risk of worsening of knee pain and radiographic change in people with knee osteoarthritis (OA). Methods The presence and laterality of foot/ankle symptoms were recorded at baseline in 1368 participants from the Osteoarthritis Initiative with symptomatic radiographic knee OA. Knee pain severity (measured using the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale) and minimum medial tibiofemoral joint space (minJSW) width measured on x-ray were assessed yearly over the subsequent four years. Associations between foot/ankle symptoms and worsening of (i) knee pain, and (ii) both knee pain and minJSW (i.e. symptomatic radiographic knee OA) were assessed using logistic regression. Results Foot/ankle symptoms in either foot/ankle significantly increased the odds of knee pain worsening (adjusted OR 1.54, 95% CI 1.25 to 1.91). Laterality analysis showed ipsilateral (adjusted OR 1.50, 95% CI 1.07 to 2.10), contralateral (adjusted OR 1.44, 95% CI 1.02 to 2.06) and bilateral foot/ankle symptoms (adjusted OR 1.61, 95% CI 1.22 to 2.13) were all associated with knee pain worsening in the follow up period. There was no association between foot/ankle symptoms and worsening of symptomatic radiographic knee OA. Conclusion The presence of foot/ankle symptoms in people with symptomatic radiographic knee OA was associated with increased risk of knee pain worsening, but not worsening of symptomatic radiographic knee OA, over the subsequent four years. Future studies should investigate whether treatment of foot/ankle symptoms reduces the risk of knee pain worsening in people with knee OA.

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A genetic study on C5-TRAF1 and progression of joint damage in rheumatoid arthritis

Cited by 133 publications

References 39 publications

Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoarthritis of the knee and typing and progression of arthritic disease

Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoarthritis of the knee and typing and progression of arthritic disease

Redox biology and the interface between bioenergetics, autophagy and circadian control of metabolism

Longitudinal association between foot and ankle symptoms and worsening of symptomatic radiographic knee osteoarthritis: data from the osteoarthritis initiative

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