Association between Paraoxonase/Arylesterase Activity of Serum PON-1 Enzyme and Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

Abstract

Background: A decrease in serum paraoxonase (PON-1) and arylesterase (ARE) activity has been reported in rheumatoid arthritis (RA) patients and linked to chronic inflammation and impaired antioxidant defense. Methods: A systematic review and meta-analysis were performed to critically appraise the current evidence on plasma/serum concentrations of PON-1 and ARE activity in RA patients and healthy controls. The Web of Science, PubMed, Scopus, and Google Scholar databases were searched from inception to November 2021. We used random-effects meta-analysis. The risk of bias was estimated using the Joanna Briggs Institute Critical Appraisal Checklist tool. The certainty of the evidence was assessed with GRADE. The study complied with the PRISMA statements and was registered in PROSPERO (CRD42022345380). Results: Seventeen studies reported PON-1 activity (1144 RA patients, 797 controls) and ten reported ARE activity (1367 RA patients, 1037 controls). RA patients had significantly lower PON-1 (SMD = −1.32, 95% CI −1.94 to −0.70; p < 0.001) and ARE activity (SMD = −0.91, 95% CI −1.37 to −0.46; p < 0.001). There was substantial heterogeneity (PON, I2 97%; ARE, 95.7%, p < 0.001 for both). There was no publication bias. The pooled SMD values did not significantly change after sensitivity analysis. The certainty of the evidence was very low due to the observational nature of the studies and the large heterogeneity. Conclusion: Our meta-analysis has shown that both serum PON-1 and ARE activity are significantly lower in RA patients, suggesting a deficit in antioxidant defense mechanisms in this disease.

Keywords: arylesterase activity; biomarkers; oxidative stress; paraoxonase activity; rheumatic diseases.

Figure 1

Flow chart describing the screening process.

Figure 2

Forest plot of studies examining serum PON-1 values of RA and controls.

Figure 3

Forest plot of studies examining serum ARE values of RA and controls.

Figure 4

Sensitivity analysis of the association between serum PON-1 values and RA. The effect size (hollow circles) for each study represents the effect size of the meta-analysis performed excluding that study.

Figure 5

Funnel plot of the 17 studies included in the meta-analysis reporting the association between serum PON-1 activity and RA.

Figure 6

Funnel plot of studies reporting associations between serum PON-1 values and RA after trimming and filling. Dummy studies and genuine studies are represented by enclosed circles and free circles, respectively.

Figure 7

Forest plot of studies examining serum PON-1 concentration in RA and controls according to continent where the study was conducted.

Figure 8

Sensitivity analysis of the association between ARE activity and RA. For each study, the displayed effect size (hollow circles) corresponds to the overall effect size computed from a meta-analysis excluding that study.

Figure 9

Funnel plot of the 10 retrieved studies evaluating the association between serum ARE concentration and RA disease.

Figure 10

Funnel plot of studies investigating the association between serum ARE values and RA disease after trimming and filling. Dummy studies and genuine studies are represented by enclosed circles and free circles, respectively.

Figure 11

Forest plot of studies examining serum ARE values in RA patients and controls is shown according to the continent where the study was conducted.