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.

White adipose tissue, a novel antirheumatic target: Clues from its secretory capability and adipectomy‐based therapy

“…It is possible that AIA‐induced PON1 changes in blood and WAT are totally different. Despite its increased concentration in blood, PON1 activity is impaired in RA patients (Bae & Lee, 2019; Erre et al, 2022). These seemingly conflicting facts hint that the role of PON1 in RA pathology needs to be further clarified.…”

Investigation of Age-Related Alterations in Brain and Serum Samples in a Healthy Aging Rat Model

“…PON enzymes, especially PON arylesterase are defined to be a critical defense system against lipid peroxidation, and a decrease in activity is a marker of increased systemic oxidative stress (Menini, 2014;Ayada, 2022;. Many clinical and experimental studies report a significant decrease in serum PON arylesterase activity in several pathological conditions such as dementia (Menini, 2014), rheumatoid arthritis (Erre, 2022), coronary artery diseases (Sofflai, 2022), cancer (Elseadya, 2002;Jasinski, 2022;Thompson, 2022), COVID-19 (Gabaldo,2022) and also in a rat model (Dube, 2022).…”

Methotrexate and cardiovascular prevention: an appraisal of the current evidence

“…The pathophysiological mechanisms underlying one of the most common and studied types of autoimmune disease, rheumatoid arthritis, 108 exhibit significant similarities with atherosclerosis. Such similarities include the presence of a vascular and systemic pro-inflammatory and pro-oxidant state, 109 – 115 reduced NO synthesis and endothelial dysfunction, 116 – 120 arterial stiffening 121 – 124 and an increased risk of arterial hypertension. 125 , 126 A critical additional element of similarity is represented by the excess production of pro-inflammatory and pro-atherogenic cytokines, for example, TNF-α, IL-1 and IL-6, that synergistically build and maintain a pro-inflammatory microenvironment in blood vessels.…”