Serum protein oxidation in patients with rheumatoid arthritis and effects of infliximab therapy.
OBJECTIVE
To examine protein oxidation in rheumatoid arthritis (RA) and evaluate its evolution after infliximab therapy in a subgroup of patients.


METHODS
Seventy-one consecutive patients with RA were included. Among them, 30 patients refractory to conventional therapy were treated with infliximab. Serum markers of oxidative stress were determined at baseline and before the infusions of infliximab at weeks 6 and 30. Baseline values were compared with those in 30 healthy volunteers.


RESULTS
Mean levels of serum carbonyl groups were significantly higher in RA patients than in controls (1.29+/-0.76 versus 0.58+/-0.39 nmol/mg of protein, p<0.0001), whereas thiol levels were found to be lower (238.3+/-61.6 versus 316.5+/-54.8 micromol/L, p<0.0001). Thiol levels inversely correlated with the disease activity score (r=-0.42, p=0.004), and with CRP values (r=-0.45, p=0.001). Immunoblots showed that albumin and heavy chain immunoglobulin were oxidized more markedly than in healthy volunteers. Significantly lower levels of thiol groups were detected in patients with refractory RA disease (208.9+/-66.8 versus 264.2+/-43.0 micromol/L, p<0.0004) but concentrations of carbonyl groups were similar. Short-term treatment with infliximab significantly decreased carbonyl groups (0.97+/-0.47 nmol/mg protein, p=0.02) and increased thiol (231.2+/-48.7 micromol/L, p=0.02) levels.


CONCLUSIONS
Our results highlight free radical protein damage in RA and a link with inflammation, as underlined by the beneficial effects of infliximab.
Lemarechal
H
H
Department of Biochemistry A, Assistance Publique-Hôpitaux de Paris, Cochin Hospital, 75014 Paris, France.
Allanore
Y
Y
Chenevier-Gobeaux
C
C
Kahan
A
A
Ekindjian
O G
OG
Borderie
D
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy*; D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D001798:Blood Proteins; D000069285:Infliximab