Increased advanced oxidation protein products in Behçet's disease: a new activity marker?

BACKGROUND: Behçet's disease (BD) is a chronic inflammatory disease with unknown pathogenesis. As various functions of neutrophils in peripheral blood, such as chemotaxis, phagocytosis and generation of reactive oxygen species (ROS) increase in BD, ROS-mediated oxidative stress related to neutrophil activation may have an important role in the pathogenesis of BD.

OBJECTIVES: To investigate the importance of neutrophil activation as the main source of oxidative stress through protein oxidation in the pathogenesis of BD, and also to investigate whether one of the products of protein oxidation, advanced oxidation protein products (AOPP), may be used as an activity marker for BD.

METHODS: Patients with BD (n = 49), at active and inactive stages, with or without evidence of uveitis, and healthy volunteers (n = 40) were entered into the study. A full blood count, peripheral blood smears, routine biochemical analyses, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) measurements were performed in all patients preceding the study. Plasma myeloperoxidase (MPO) activity, representing neutrophil activation, and biomarkers of oxidative stress reflecting protein oxidation, such as levels of AOPP and thiol, were measured spectrophotometrically. Statistical comparisons were made using Mann-Whitney U-tests, Student's t-tests, anova/post-anova tests and correlation analyses.

RESULTS: In all patients, the results of full blood count, peripheral blood smears and routine biochemical analyses were in the normal range, but mean values of CRP and ESR were higher than laboratory reference values. Plasma MPO activity and AOPP levels were found to be higher and thiol values lower in the total patient group and individual subgroups than in controls. Patients with active BD had significantly higher MPO and AOPP levels and lower thiol levels than patients with inactive BD. There was no difference between uveitis-positive and uveitis-negative subgroups in MPO and thiol levels, but AOPP levels were lower in the latter group. Patients with active BD +/- uveitis were shown to have increased MPO and AOPP but decreased thiol levels in comparison with the inactive BD, uveitis-negative subgroup. There were strong positive correlations between ESR and CRP, ESR and MPO, ESR and thiol, ESR and AOPP, CRP and MPO, CRP and AOPP, MPO and AOPP, and thiol and AOPP levels in patients with BD.

CONCLUSIONS: Based on this first study, in which MPO-mediated AOPP formation has been demonstrated, it may be suggested that activated neutrophils may play an important role in the pathogenesis of BD and that chlorinated oxidants of neutrophil origin may lead to oxidative stress, notably protein oxidation. Therefore, AOPP may be a useful marker for monitoring the progress and the severity of the disease activity.