A discovery of screening markers for rheumatoid arthritis by liquid chromatography mass spectrometry: A metabolomic approach

Lee, Yoojin; Mun, Sora; Lee, You-Rim; Lee, Seungyeon; Kwon, Sohyen; Kim, Doojin; Lim, Myung-Jae; Kang, Hee-Gyoo; Lee, Jiyeong

doi:10.1111/1756-185x.13935

Cited by 10 publications

(5 citation statements)

References 53 publications

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“…However, while succinate was detected in the synovial fluid in a separate comparison of several inflammatory and non-inflammatory arthritis types, no metabolic distinction was found between patient groups in this study ( 112 ). Metabolomic studies of plasma and serum found no significant differences in succinate levels between RA patients and controls ( 91 , 113 – 115 ), or between RA patient groups with differing disease activity ( 114 ), meaning that succinate levels are unlikely to be a useful clinical biomarker of disease. It is unclear whether these different results represent mechanistic differences in disease processes between the circulation and synovium, or if the power of the studies was insufficient to detect differences in this metabolite in serum samples.…”

Section: Tca Cycle Metabolitesmentioning

confidence: 98%

Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis

et al. 2021

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Mitochondria are major energy-producing organelles that have central roles in cellular metabolism. They also act as important signalling hubs, and their dynamic regulation in response to stress signals helps to dictate the stress response of the cell. Rheumatoid arthritis is an inflammatory and autoimmune disease with high prevalence and complex aetiology. Mitochondrial activity affects differentiation, activation and survival of immune and non-immune cells that contribute to the pathogenesis of this disease. This review outlines what is known about the role of mitochondria in rheumatoid arthritis pathogenesis, and how current and future therapeutic strategies can function through modulation of mitochondrial activity. We also highlight areas of this topic that warrant further study. As producers of energy and of metabolites such as succinate and citrate, mitochondria help to shape the inflammatory phenotype of leukocytes during disease. Mitochondrial components can directly stimulate immune receptors by acting as damage-associated molecular patterns, which could represent an initiating factor for the development of sterile inflammation. Mitochondria are also an important source of intracellular reactive oxygen species, and facilitate the activation of the NLRP3 inflammasome, which produces cytokines linked to disease symptoms in rheumatoid arthritis. The fact that mitochondria contain their own genetic material renders them susceptible to mutation, which can propagate their dysfunction and immunostimulatory potential. Several drugs currently used for the treatment of rheumatoid arthritis regulate mitochondrial function either directly or indirectly. These actions contribute to their immunomodulatory functions, but can also lead to adverse effects. Metabolic and mitochondrial pathways are attractive targets for future anti-rheumatic drugs, however many questions still remain about the precise role of mitochondrial activity in different cell types in rheumatoid arthritis.

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Section: Tca Cycle Metabolitesmentioning

confidence: 98%

Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis

et al. 2021

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“…Of note, these metabolites were signi cantly reduced in collagen-induced arthritis mice compared to controls 9 . We also identi ed DHEA sulfate as the metabolite with the lowest RA/HC ratio, in alignment with the literature 10 .…”

Section: Discussionmentioning

confidence: 55%

Red blood cell metabolomics identify ergothioneine as a key metabolite in DMARD-naïve rheumatoid arthritis and response to methotrexate

Sigaux,

Junot,

Boissier

et al. 2024

Preprint

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Using a new red blood cell (RBC) metabolite extraction protocol, we performed a metabolomic analysis on RBCs in rheumatoid arthritis (RA) patients treated or not with methotrexate (MTX), with the two following objectives: to compare the RBC metabolic profiles of MTX-naïve RA patients and healthy controls (HC), and to investigate whether RBC profiles before and after MTX treatment in RA differed between responders and non-responders. Plasma analysis was performed in parallel. Metabolites were extracted and identified in RBCs and plasma by liquid chromatography-mass spectrometry. We compared the metabolomic fingerprints of 31 DMARD-naïve RA patients and 39 HCs. We also compared the RBC and plasma metabolomes of 25 RA patients who responded or not to MTX therapy before (M0) and after a 3-month treatment period (M3). Significance was determined by Storey’s false discovery rate (FDR) q-values to correct for multiple testing. RA patients and HCs differed in the metabolomic signature of RBCs. The signature mainly contained amino acids (AA). Eleven metabolites, including 4 metabolites belonging to the carbohydrate subclass and 2 amino acids (creatine and valine) showed accumulation in RBCs from RA patients. Conversely, citrulline (fold change=0.83; q=0.025), histidine (fold change=0.86; q=0.014) and ergothioneine (EGT) (fold change=0.66; q=0.024), were lower in RA. Among RA patients undergoing MTX treatment pre-treatment (M0), EGT values were significantly lower in non-responders. In conclusion, low RBC levels of EGT, a food-derived AA barely detectable in plasma, characterize DMARD naïve RA patients and lack of response to MTX treatment.

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“…At the same time, this inflammatory reaction will promote each other with phosphoethanolamine (PE) resulting in the increase of PE [ 20 ], and anandamide is the metabolite of PE [ 21 ], but our study also found different results. Androsterone sulfate and dehydroepiandrosterone (DHEA) sulfate may be related to the development of inflammation and immunoregulatory activity [ 22 ], but our study shows the opposite trend to other inflammatory diseases. Some studies have found that when the body is in the state of oxidative stress, the body will inhibit the synthesis of coenzyme A in cells [ 23 ].…”

Section: Discussionmentioning

confidence: 66%

A metabonomic study to explore potential markers of asymptomatic hyperuricemia and acute gouty arthritis

Wang

Kou

Zhang³

et al. 2023

J Orthop Surg Res

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Background Acute gouty arthritis (AGA) is a metabolic disease with acute arthritis as its main manifestation. However, the pathogenesis of asymptomatic hyperuricemia (HUA) to AGA is still unclear, and metabolic markers are needed to early predict and diagnose. In this study, gas chromatography (GC)/liquid chromatography (LC)–mass spectrometry (MS) was used to reveal the changes of serum metabolites from healthy people to HUA and then to AGA, and to find the pathophysiological mechanism and biological markers. Methods Fifty samples were included in AGA, HUA, and healthy control group, respectively. The metabolites in serum samples were detected by GC/LC–MS. According to the statistics of pairwise grouping, the statistically significant differential metabolites were obtained by the combination of multidimensional analysis and one-dimensional analysis. Search the selected metabolites in KEGG database, determine the involved metabolic pathways, and draw the metabolic pathway map in combination with relevant literature. Results Using metabonomics technology, 23 different serum metabolic markers related to AGA and HUA were found, mainly related to uric acid metabolism and inflammatory response caused by HUA/AGA. Three of them are completely different from the previous gout studies, nine metabolites with different trends from conventional inflammation. Conclusions In conclusion, we analyzed 150 serum samples from AGA, HUA, and healthy control group by GC/LC–MS to explore the changes of these differential metabolites and metabolic pathways, suggesting that the disease progression may involve the changes of biomarkers, which may provide a basis for disease risk prediction and early diagnosis.

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A discovery of screening markers for rheumatoid arthritis by liquid chromatography mass spectrometry: A metabolomic approach

Cited by 10 publications

References 53 publications

Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis

Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis

Red blood cell metabolomics identify ergothioneine as a key metabolite in DMARD-naïve rheumatoid arthritis and response to methotrexate

A metabonomic study to explore potential markers of asymptomatic hyperuricemia and acute gouty arthritis

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