Myeloperoxidase and oxidative stress in rheumatoid arthritis.
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).


CONCLUSIONS
MPO is elevated in patients with RA and promotes oxidative stress through the production of hypochlorous acid.
Department of Medicine, University of Otago, Christchurch, Christchurch 8140, New Zealand. lisa.stamp@cdhb.govt.nz
Lisa K
LK
Stamp
Irada
I
Khalilova
Joanna M
JM
Tarr
Revathy
R
Senthilmohan
Rufus
R
Turner
Richard C
RC
Haigh
Paul G
PG
Winyard
Anthony J
AJ
Kettle
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D009195:Peroxidase / Q000097:blood / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism*
D017382:Reactive Oxygen Species; D009195:Peroxidase