Tumor necrosis factor-alpha stimulated gene-6: A biomarker reflecting disease activity in rheumatoid arthritis.

BACKGROUND: To explore the serum tumor necrosis factor-alpha stimulated gene-6 (TSG-6) level and its association with disease activity in rheumatoid arthritis (RA) patients. METHODS: We recruited 176 RA patients, 178 non-RA patients (lupus erythematosus, osteoarthritis, ulcerative colitis, ankylosing spondylitis and psoriasis) and 71 healthy subjects. Serum TSG-6 levels were detected by enzyme-linked immunosorbent assay (ELISA). RA patients were divided into inactive RA and active RA groups by disease activity score of 28 joints based on C-reactive protein (DAS28-CRP). The receiver operating characteristic (ROC) curve and Spearman's rank correlation test analyzed the correlation between TSG-6 concentration and RA disease activity. RESULTS: Tumor necrosis factor-alpha stimulated gene-6 levels in the RA group were increased (p < 0.01). TSG-6 concentrations indicated an upward tendency with increased disease activity; The area under the curve (AUC) of TSG-6 for diagnosing RA and assessing the severity of RA were 0.78 and 0.80, respectively; The combination of TSG-6 and anti-mutated citrullinated vimentin antibodies (anti-MCV) (sensitivity:98.4%)improved the diagnostic accuracy of RA. Binary logistic regression analysis showed that TSG-6 was an independent risk factor related to the severity of RA, and OR (95% CI) was 1.2 (1.003-1.453). CONCLUSION: The TSG-6 levels in RA patients were elevated and related to disease activity. Therefore, TSG-6 may serve as a new potential biomarker for evaluating RA disease activity.

Meta-analysis: compared with anti-CCP and rheumatoid factor, could anti-MCV be the next biomarker in the rheumatoid arthritis classification criteria?

Background Previous reviews of the diagnosis for rheumatoid arthritis (RA) have not compared anti-mutated citrullinated vimentin (MCV) with anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) in respect of sensitivity, specificity and the area under the curve (AUC) against disease controls for differential diagnosis. This meta-analysis aims to evaluate the value of anti-MCV in the diagnosis for RA, the combined sensitivity of anti-MCV and anti-CCP, and certain clinical characteristics related to the performance of anti-MCV. Methods Medline, Embase, Cochrane Library and Web of Science were searched for articles published up to 25 August 2018. A total of 33 studies including 6044 RA patients and 5094 healthy or disease controls achieved inclusive criteria. QUADAS-2 was applied to evaluate the quality of the included studies. The bivariate random effects model was employed in primary data synthesis to evaluate the diagnostic performance. Results The sensitivity of anti-MCV, anti-CCP and RF in RA diagnosis against a disease control group was 0.71, 0.71, 0.77, with the specificity of 0.89, 0.95, 0.73, and the AUC of the SROC of 0.89, 0.95, 0.82, respectively. The predesign of the primary study and diagnostic criteria were statistically significant as sources of heterogeneity. Anti-MCV and anti-CCP tests demonstrated a sensitivity of 0.77 when performed in parallel, with a sensitivity of 0.60 when performed in series; whereas, the combination of anti-MCV and RF presented a sensitivity of 0.64 when used in series. Conclusions Anti-MCV demonstrates comparable diagnostic value to anti-CCP and RF, thus it can be an effective diagnostic marker for RA and may be written into the next authoritative criteria.

Serum sirtuin-1 a potential marker in the diagnosis of rheumatoid arthritis.

Introduction: To explore the value of serum sirtuin-1 (SIRT1) in the diagnosis and evaluation of joint mobility of rheumatoid arthritis (RA). Materials and Methods: Serum was randomly obtained from 212 RA patients,210 non-RA patients and 58 healthy controls in a large tertiary first-class hospital in Jiangxi province from November 2021 to June 2022. The level of serum Sirt1,anti-cyclic citrulline polypeptide antibody (anti-CCP), anti-mutant citrulline vimentin antibody (anti-MCV), rheumatoid factor (RF),high-mobility group box 1 (HMGB1), collagen triple helix repeat containing 1 (CTHRC1), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were detected by ELISA, to explore the correlation between them and their value in the diagnosis and evaluation of joint range of motion of RA and statistically analyse their diagnostic efficiency. Results: ① The level of all markers was higher in the RA group than in the non-RA group and the healthy controls (p < 0.05). ② The AUC of the SIRT1 was 0.882, second only to the anti-MCV and anti-CCP. ③ The anti-CCP showed the highest sensitivity to RA diagnosis of 0.948. The specificity and positive predictive value of SIRT1 for the diagnosis of RA were the highest, which are 0.959 and 0.934 respectively. ④ In serial combination, SIRT1/anti-CCP、SIRT1/anti-MCV showed the highest specificity.SIRT1/anti-CCP in parallel combination had the highest sensitivity. ⑤ SIRT1 showed a significant correlation with other markers and DAS28 scores (p < 0.01). Conclusion: SIRT1 can be used as a new serological marker for RA diagnosis, which has a significant correlation with RA joint mobility and has a certain reference value in RA differential diagnosis, providing a new detection basis for RA differential diagnosis.

The clinical value of serum sirtuin-1 in the diagnosis of rheumatoid arthritis: a pilot study.

Introduction: Cell biology studies, animal models and other data suggest a role for sirtuin-1 in the pathogenesis of rheumatoid arthritis (RA). We hypothesized the clinical significance of serum sirtuin-1 in this disease.Methods: Serum was obtained from 141 RA patients, 144 non-RA patients and 88 healthy controls. Sirtuin-1, anti-mutant citrulline vimentin antibody (anti-MCV), anti-cyclic citrulline polypeptide antibody (anti-CCP), rheumatoid factor and C-reactive protein were measured by immunological methods, and erythrocyte sedimentation rate was determined by the Westergren method.Results: All markers were higher in the RA group than in the non-RA group and the healthy control group (P < 0.01). The specificity of sirtuin-1 for the diagnosis of RA was 97% (the highest among all markers), sensitivity was 71%. In ROC curve analysis, the AUCs (95% CI) of sirtuin-1, anti-CCP and anti-MCV were 0.87 (0.82-0.91), 0.91 (0.88-0.94) and 0.92 (0.89-0.95) respectively (all p < 0.01). The combination of sirtuin-1and anti-MCV gave the highest Youden index of 0.79, whilst Cox regression showed sirtuin-1 and rheumatoid factor were the strongest independent predictors of RA.Conclusions: Serum sirtuin-1 is increased in RA, and may have a place is the diagnosis of this disease when combined with other markers.

Clinical diagnostic significance of 14-3-3η protein, high-mobility group box-1, anti-cyclic citrullinated peptide antibodies, anti-mutated citrullinated vimentin antibodies and rheumatoid factor in rheumatoid arthritis.

Introduction: Circulating markers of rheumatoid arthritis (RA) include the 14-3-3η protein, high-mobility group box-1 (HMGB1), anti-cyclic citrullinated peptide (anti-CCP) antibodies, anti-mutated citrullinated vimentin (anti-MCV) antibodies and rheumatoid factor (RF). We set out to determine which two markers in combination provided best discriminatory power for this disease.Methods: We recruited 108 RA patients, 102 non-RA patients (SLE, AS, Sjogren's syndrome, MCTD) and 90 healthy controls. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and the Youden index of each analyte were calculated and binary logistic regression analysis and receiver operating characteristic (ROC) curve were performed to evaluate their diagnostic value for RA alone and in paired combination.Results: As expected, all markers were elevated in RA patients (P < 0.05). Binary logistic regression analysis showed that 14-3-3η had the highest odds ratio (95% CI) at 2.4 (1.9-2.8). Anti-CCP and anti-MCV had the highest areas under the curves [AUC (95% CI)] at 0.85 (0.78-0.90) and 0.85 (0.78-0.91) respectively (both P < 0.001). In serial detection (one marker followed by another), no combination had a Youden index >0.6. In parallel analysis (both considered together) several combinations had a Youden index >0.7, of which the highest (0.78) was anti-CCP with anti-MCV, with a sensitivity of 93.3% and specificity of 84.7%.Conclusions: Despite individual increases in serum 14-3-3η, HMGB1, anti-CCP, anti-MCV and RF, the combination of anti-CCP and anti-MCV might be of great help for diagnostic in RA, and so should be considered as routine tests for this disease.

Autoantibody and metalloproteinase activity in early arthritis.

OBJECTIVES: The aim of the study was to evaluate the frequency of anti-mutated citrullinated vimentin antibodies (a-Sa), anti-citrullinated α-enolase peptide 1 antibodies (a-CEP-1), anti-filaggrin antibodies (AFAs), heterogeneous nuclear ribonucleoprotein compies/anti-RA33-antibodies (a-hnRNP/RA33), anti-carbamylated protein antibodies (a-CarP), and metalloproteinase (MMPs) activity in patients with early inflammatory arthritis (EIA). METHODS: Seventy-four patients with EIA: 51 diagnosed with RA (rheumatoid arthritis) and 23 with UA (undifferentiated arthritis), and 20 healthy volunteers were enrolled to the study. Inflammatory markers, rheumatoid factor (RF), and antibodies mentioned above were assessed in all patients. RESULTS: In the EIA group, we observed significantly higher concentration of a-CEP-1 (65.8 ± 111.6 RU/mL) than in controls (2.0 ± 0.0 RU/mL). In RF(+) RA patients, we observed higher concentration of a-Sa and a-CEP-1 than in other groups. A-Sa were positive in 69% of RF(+) RA, 37% of RF(-) RA, 26% of UA patients and in 10% of controls. A-CEP-1 were positive in 77% of RF(+) RA patients, in 56% of RF(-) RA patients, in 8.7% of UA patients, but they were negative in controls. In patients with RF(+) RA, positive a-CarP were present statistically significantly more often than in RF (-) RA patients. No statistically significant difference in frequency of a-hnRNP/RA33 and AFA between RF(+) RA, RF(-) RA, and UA was observed. CONCLUSIONS: Our results suggest that a-CEP-1 may help in differentiation between RF(-) RA and UA. a-CEP-1 and a-Sa may be useful while diagnosing EIA. a-CarP may be used in differentiation of RA RF(-) and UA. However, a follow-up study is needed to evaluate the prognostic value of analyzed antibodies.