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Myeloperoxidase and oxidative stress in rheumatoid arthritis
Lisa K Stamp1, Irada Khalilova, Joanna M Tarr
1Department of Medicine, University of Otago, Christchurch, Christchurch 8140, New Zealand. lisa.stamp@cdhb.govt.nz
Objective:
To determine whether MPO contributes to oxidative stress and disease activity in RA and whether it produces hypochlorous acid in SF.
Methods:
Plasma and where possible SF were collected from 77 RA patients while 120 healthy controls supplied plasma only. MPO and protein carbonyls were measured by ELISAs. 3-Chlorotyrosine in proteins and allantoin in plasma were measured by mass spectrometry.
Results:
Plasma MPO concentrations were significantly higher in patients with RA compared with healthy controls [10.8 ng/ml, inter-quartile range (IQR): 7.2-14.2; P<0.05], but there was no significant difference in plasma MPO protein concentrations between RA patients with high disease activity (HDA; DAS-28 >3.2) and those with low disease activity (LDA; DAS-28 ≤ 3.2) (HDA 27.9 ng/ml, 20.2-34.1 vs LDA 22.1 ng/ml, 16.9-34.9; P>0.05). There was a significant relationship between plasma MPO and DAS-28 (r=0.35; P=0.005). Plasma protein carbonyls and allantoin were significantly higher in patients with RA compared with the healthy controls. MPO protein was significantly higher in SF compared with plasma (median 624.0 ng/ml, IQR 258.4-2433.0 vs 30.2 ng/ml, IQR 25.1-50.9; P<0.0001). The MPO present in SF was mostly active. 3-Chlorotyrosine, a specific biomarker of hypochlorous acid, was present in proteins from SF and related to the concentration of MPO (r=0.69; P=0.001). Protein carbonyls in SF were associated with MPO protein concentration (r=0.40; P=0.019) and 3-chlorotyrosine (r=0.66; P=0.003).
Conclusion:
MPO is elevated in patients with RA and promotes oxidative stress through the production of hypochlorous acid.
Insights
Myeloperoxidase (MPO) is elevated in rheumatoid arthritis (RA) patients, contributing to oxidative stress via hypochlorous acid production in synovial fluid. This finding highlights MPO
Area of Science:
- Biochemistry
- Immunology
- Rheumatology
Background:
- Rheumatoid arthritis (RA) is characterized by chronic inflammation and joint damage.
- Oxidative stress plays a significant role in the pathogenesis of RA.
- Myeloperoxidase (MPO) is an enzyme implicated in inflammatory processes.
Purpose of the Study:
- To investigate the role of MPO in oxidative stress and disease activity in RA patients.
- To determine if MPO produces hypochlorous acid (HOCl) in synovial fluid (SF).
Main Methods:
- Collected plasma and SF from 77 RA patients and plasma from 120 healthy controls.
- Measured MPO, protein carbonyls, 3-chlorotyrosine, and allantoin using ELISAs and mass spectrometry.
- Analyzed MPO levels in relation to disease activity scores (DAS-28).
Main Results:
- Plasma MPO concentrations were significantly higher in RA patients compared to controls.
- MPO levels in SF were substantially higher than in plasma and were mostly active.
- 3-Chlorotyrosine, a marker of HOCl, was detected in SF proteins and correlated with MPO concentration.
- SF protein carbonyls, indicative of oxidative stress, were associated with MPO and 3-chlorotyrosine levels.
Conclusions:
- MPO is elevated in RA patients and contributes to oxidative stress.
- MPO produces hypochlorous acid in the synovial fluid of RA patients.
- MPO-derived HOCl is a key mediator of oxidative damage in RA joints.
