Interplay of redox imbalance with matrix gelatinases in neutrophils and their association with disease severity in rheumatoid arthritis patients

Rheumatoid arthritis (RA) etiopathogenesis still remains complex, but involvement of several immune cells is evident. Present study focusses on evaluation of polymorphonuclear neutrophils (PMNs) in RA patients and healthy controls. From generation of oxidative species, release of inflammatory cytokines and matrix-degrading proteases, PMNs possess the ability to mediate immunological responses. Intracellular and mitochondrial ROS in PMNs and other oxidative parameters including catalase, superoxide dismutase, glutathione peroxidase, reduced glutathione and lipid peroxidation were measured in PMNs and serum samples. Gene regulation studies involved in oxidative (Keap1 and Nrf2) and degradative pathways (MMP2 and MMP9) were done using DNA methylation analysis. Intracellular expression levels of Keap1, Nrf2, Dnmt1, MMP2, and MMP9 were analyzed using flow-cytometry in patients and controls. Moreover, serum levels of pro-inflammatory cytokines IL-1 beta, IL-6, and TNF-alpha were also measured. Comparative measurements amongst patients and controls were statistically analyzed, and correlations were made with disease severity scores (DAS28 ESR).

Automated summary

This study evaluates the role of polymorphonuclear neutrophils (PMNs) in patients with rheumatoid arthritis (RA) and healthy controls. The results demonstrate that PMNs play an important role in mediating immune responses and are associated with gene regulation involved in oxidative and degradative pathways. Additionally, the study found significantly elevated levels of pro-inflammatory cytokines in the serum of RA patients, which correlated with disease severity.