PMID- 22814531 OWN - NLM STAT- MEDLINE DCOM- 20121207 LR - 20120924 IS - 1462-0332 (Electronic) IS - 1462-0324 (Linking) VI - 51 IP - 10 DP - 2012 Oct TI - Myeloperoxidase and oxidative stress in rheumatoid arthritis. PG - 1796-803 AB - 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 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. FAU - Stamp, Lisa K AU - Stamp LK AD - Department of Medicine, University of Otago, Christchurch, Christchurch 8140, New Zealand. lisa.stamp@cdhb.govt.nz FAU - Khalilova, Irada AU - Khalilova I FAU - Tarr, Joanna M AU - Tarr JM FAU - Senthilmohan, Revathy AU - Senthilmohan R FAU - Turner, Rufus AU - Turner R FAU - Haigh, Richard C AU - Haigh RC FAU - Winyard, Paul G AU - Winyard PG FAU - Kettle, Anthony J AU - Kettle AJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120719 PL - England TA - Rheumatology (Oxford) JT - Rheumatology (Oxford, England) JID - 100883501 RN - 0 (Reactive Oxygen Species) RN - EC 1.11.1.7 (Peroxidase) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Arthritis, Rheumatoid/blood/*metabolism MH - Female MH - Humans MH - Male MH - Middle Aged MH - Oxidative Stress/*physiology MH - Peroxidase/blood/*metabolism MH - Reactive Oxygen Species/metabolism MH - Synovial Fluid/*metabolism EDAT- 2012/07/21 06:00 MHDA- 2012/12/12 06:00 CRDT- 2012/07/21 06:00 PHST- 2012/07/21 06:00 [entrez] PHST- 2012/07/21 06:00 [pubmed] PHST- 2012/12/12 06:00 [medline] AID - kes193 [pii] AID - 10.1093/rheumatology/kes193 [doi] PST - ppublish SO - Rheumatology (Oxford). 2012 Oct;51(10):1796-803. doi: 10.1093/rheumatology/kes193. Epub 2012 Jul 19.