Correlation Between Total Bilirubin, Total Bilirubin/Albumin Ratio with Disease Activity in Patients with Rheumatoid Arthritis

Zhang, Hui; Yang, Guizhao; Jiang, Rongqiong; Feng, Dan; Li, Yuqin; Chen, Yong; Yuan, Guohua

doi:10.2147/ijgm.s393273

Cited by 4 publications

(8 citation statements)

References 42 publications

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“…From a total of 2,805 articles initially identified, 2,783 were excluded because they were either duplicates or irrelevant. After a full-text review of the remaining 22 articles, a further two were excluded because of missing data and three because they did not have a case-control design, leaving 17 studies for further analysis ( 33 – 49 ) ( Figure 1 ; Table 1 ). The risk of bias was considered low in all studies ( Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

The role of bilirubin as a biomarker of rheumatic diseases: a systematic review and meta-analysis

Zinellu,

Mangoni

2024

Front. Immunol.

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The identification of novel, yet easily measurable biomarkers of inflammation and oxidative stress might assist in the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a systematic review and meta-analysis of studies investigating the circulating concentrations of bilirubin, the end product of heme metabolism and a potent endogenous antioxidant with anti-inflammatory properties, in patients with RDs and healthy controls. The electronic databases PubMed, Scopus, and Web of Science were searched from inception to 31 December 2023 for relevant articles. We evaluated the risk of bias and the certainty of evidence using the Joanna Briggs Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation Working Group system, respectively. In 17 eligible studies, all with low risk of bias, compared to controls, patients with RDs had significantly lower concentrations of total bilirubin (standard mean difference, SMD=-0.68, 95% CI -0.91 to -0.44, p<0.001; I2 = 92.5%, p<0.001; low certainty of evidence), direct (conjugated) bilirubin (SMD=-0.67, 95% CI -0.92 to -0.41, p<0.001; I2 = 81.7%, p<0.001; very low certainty of evidence), and the active antioxidant and anti-inflammatory indirect (unconjugated) form of bilirubin (SMD=-0.71, 95% CI -1.18 to -0.24, p=0.003; I2 = 95.1%, p<0.001; very low certainty of evidence). The results of the meta-analysis were stable in sensitivity analysis. In meta-regression, there were no significant associations between the SMD of total bilirubin and several clinical and demographic characteristics, including age, male to female ratio, number of participants, liver enzymes and erythrocyte sedimentation rate. In subgroup analysis, the SMD of total bilirubin was significant across a range of RDs, including rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren syndrome, and myositis. Therefore, the results of our systematic review and meta-analysis suggests that the reductions in bilirubin concentrations observed in patients with RDs reflect a state of impaired antioxidant and anti-inflammatory defence due to bilirubin consumption and highlight the promising role of this endogenous product as a biomarker of RDs.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023500649.

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Section: Resultsmentioning

confidence: 99%

The role of bilirubin as a biomarker of rheumatic diseases: a systematic review and meta-analysis

Zinellu,

Mangoni

2024

Front. Immunol.

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“…The concentration of bilirubin was described as inversely proportional to the disease activity [46]. Thus, the increased concentration of bilirubin within the physiological range after an efficient treatment start might indicate the beneficial effect of the treatment that might be supported by the antioxidant effects of bilirubin [46,47]. Based on the literature, we expected an effect on liver enzymes [48].…”

Section: Discussionmentioning

confidence: 97%

“…According to the literature, the concentration of bilirubin in RA patients was described as lower compared to healthy individuals [45]. The concentration of bilirubin was described as inversely proportional to the disease activity [46]. Thus, the increased concentration of bilirubin within the physiological range after an efficient treatment start might indicate the beneficial effect of the treatment that might be supported by the antioxidant effects of bilirubin [46,47].…”

Section: Discussionmentioning

confidence: 99%

Metabolic Effects of Anti-TNF-α Treatment in Rheumatoid Arthritis

Macáková,

Tekeľová,

Mlynáriková

et al. 2023

Diseases

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Rheumatoid arthritis (RA) is associated with high cardiovascular mortality. It is not clear whether the metabolic consequences of chronic inflammation are involved. Biological disease-modifying anti-rheumatic drugs (bDMARDs) are highly efficient in the treatment of inflammation in RA. In this study, we aimed to describe the metabolic effects of anti-TNF-α treatment in RA patients. The clinical status of 16 patients was assessed using disease activity score-28 (DAS28) and C-reactive protein (CRP). Plasma samples were collected before treatment with anti-TNF-α treatment as well as after three and six months of treatment. Markers of lipid and glucose metabolism, as well as renal biomarkers, were assessed using standard biochemistry. ELISA was used for the quantification of insulin, leptin, and adiponectin. Although fasting insulin decreased by 14% at the end of the study, most of the analyzed parameters did not show any statistically or clinically significant dynamics. The exception was total bilirubin and cholesterol, which increased by 53% and 14%, respectively, after six months of treatment with anti-TNF-α treatment. Anti-TNF-α treatment did not induce major metabolic changes despite the strong anti-inflammatory and clinical symptoms of RA. Further studies will show whether longer observations are required for the detection of the metabolic effects of the anti-inflammatory treatment. Additional research is needed to understand the observed effect of bilirubin as an important endogenous antioxidant.

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“… 2 Oxidative stress generates excessive free radicals that oxidize other molecules in the body, for example, excessive free radicals in RA patients reduce the antioxidant level of the body and accelerate the progression of bone destruction. 3 We demonstrated that the low expression of LINC00638 regulates the Nrf2/HO‐1 signaling pathway, triggering inflammation in RA and influencing its oxidative stress response. 4 The Nrf2/HO‐1 signaling pathway can also affect antioxidant enzymes, regulate cellular redox responses, and influence other antioxidant enzymes.…”

Section: Introductionmentioning

confidence: 85%

“…Activated fibroblastic synoviocytes (FLS), and inflammatory and oxidative factors are found to be involved in the inflammatory mechanisms of RA during the bone destruction and synovitis of RA 2 . Oxidative stress generates excessive free radicals that oxidize other molecules in the body, for example, excessive free radicals in RA patients reduce the antioxidant level of the body and accelerate the progression of bone destruction 3 . We demonstrated that the low expression of LINC00638 regulates the Nrf2/HO‐1 signaling pathway, triggering inflammation in RA and influencing its oxidative stress response 4 .…”

Section: Introductionmentioning

confidence: 99%

Exploring the effect of LncRNA DANCR to regulate the Keap1‐Nrf2/ARE pathway on oxidative stress in rheumatoid arthritis

Cai,

Sun,

Wang

et al. 2024

Immunity Inflam & Disease

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IntroductionAberrant expression of long noncoding RNAs (LncRNAs) can regulate oxidative stress in rheumatoid arthritis (RA). This study focused on investigating the effects of LncRNA differentiation antagonizing nonprotein coding RNA (DANCR) regulation of Keap1‐Nrf2/ARE pathway on inflammation and oxidative stress in RA.MethodsThe levels of LncRNA DANCR/miR‐486‐3p/Keap1 in peripheral blood of 30 RA groups and 30 normal subjects were examined, and the association of LncRNA DANCR with inflammatory indicators of RA was investigated. We stimulated fibroblast‐like synoviocytes (FLS) from RA patients with tumor necrosis factor α and subsequently performed in vitro cellular assays to construct overexpression plasmids and small interfering RNAs of LncRNA DANCR to investigate the relationship between LncRNA DANCR and FLSs viability and migration in RA, as well as the effects on cellular oxidative stress factors and Keap1‐Nrf2/ARE pathway; molecular biology analysis was used to predict microRNAs that can bind LncRNA DANCR, and luciferase verified the binding sites of LncRNA DANCR with Keap1 and miR‐486‐3p; to further refine the gene and protein expression results, we used reverse transcription‐quantitative polymerase chain reaction and immunoblotting assays.ResultsIn both groups of peripheral blood mononuclear cells, the expression levels of LncRNA DANCR and Keap1 messenger RNA were higher in the RA group than in the normal control group, and the opposite was true for miR‐486‐3p; LncRNA DANCR was positively correlated with total antioxidant capacity (TAOC), IL6, IL17, malondialdehyde (MDA), but not with IL11, rheumatoid factor, cyclic citrullinated peptide, superoxide dismutase (SOD), with 28‐joint disease activity score, reactive oxygen species, C‐reactive protein, and erythrocyte sedimentation rate were negatively correlated; overexpression of LncRNA DANCR stimulated the Keap1‐Nrf2/ARE pathway, decreased the expression of IL10, SOD, TAOC, and increased the expression levels of MDA, IL11, IL‐17, PD‐L1, and silencing of LncRNA DANCR was the opposite, but knockdown of miR‐486‐3p or overexpression of keap1 reversed the expression of the above‐mentioned inflammatory and oxidative factors. In addition, pcDNA‐DANCR clearly showed stronger cell invasion and migration ability and exacerbated its inflammatory response, which may be related to the regulatory role of miR‐486‐3p and Keap1‐Nrf2/ARE signaling pathway, and we verified their targeting relationship using dual luciferase, showing that DANCR could regulate Keap1‐Nrf2/ARE through miR‐486‐3p modulates the Keap1‐Nrf2/ARE pathway and affects inflammatory and oxidative responses in RA patients.ConclusionThe low‐expressed LncRNA DANCR may regulate the Keap1‐Nrf2/ARE pathway and suppress the inflammatory and oxidative responses in RA patients.

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Correlation Between Total Bilirubin, Total Bilirubin/Albumin Ratio with Disease Activity in Patients with Rheumatoid Arthritis

Cited by 4 publications

References 42 publications

The role of bilirubin as a biomarker of rheumatic diseases: a systematic review and meta-analysis

The role of bilirubin as a biomarker of rheumatic diseases: a systematic review and meta-analysis

Metabolic Effects of Anti-TNF-α Treatment in Rheumatoid Arthritis

Exploring the effect of LncRNA DANCR to regulate the Keap1‐Nrf2/ARE pathway on oxidative stress in rheumatoid arthritis

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