Myeloperoxidase and oxidative stress in rheumatoid arthritis
Myeloperoxidase and oxidative stress in rheumatoid arthritis
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DOI：
10.1093/rheumatology/kes193
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发表时间：
2012-10-01
期刊：
影响因子：
5.5
通讯作者：
Kettle, Anthony J.
中科院分区：
文献类型：
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作者：
Stamp, Lisa K.;Khalilova, Irada;Kettle, Anthony J.
Objective.为了确定MPO是否有助于氧化应激和疾病活动性在RA和是否产生次氯酸在SF。从77例RA患者中收集血浆和SF（如可能），而120例健康对照仅提供血浆。酶联免疫吸附法测定MPO和蛋白质羰基。3-用质谱法测定蛋白质中的氯酪氨酸和血浆中的尿囊素。RA患者血浆MPO浓度显著高于健康对照组[10.8 ng/ml，四分位数间距（IQR）：7.2-14.2; P < 0.05]，但高疾病活动性RA患者血浆MPO蛋白浓度无显著差异（HDA; DAS-28 > 3.2）和低疾病活动度（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）。血浆MPO与DAS-28之间有显著相关性（r = 0.35; P = 0.005）。血浆蛋白羰基和尿囊素与RA患者相比，健康对照组显着升高。SF中MPO蛋白显著高于血浆（中位数624.0 ng/ml，IQR 258.4-2433.0 vs 30.2 ng/ml，IQR 25.1-50.9; P < 0.0001）。SF中MPO活性最强。SF蛋白质中存在次氯酸的特异性生物标志物3-氯酪氨酸，且与MPO浓度相关（r = 0.69; P = 0.001）。SF中蛋白羰基与MPO蛋白浓度（r = 0.40; P = 0.019）和3-氯酪氨酸（r = 0.66; P = 0.003）相关。MPO在RA患者中升高，并通过产生次氯酸促进氧化应激。
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.