C Yazici1, K Köse, M Calis, S Kuzugüden, M Kirnap. 1. Department of Biochemistry, Faculty of Medicine, Erciyes University, Kayseri, Turkey. yazici@erciyes.edu.tr
Abstract
OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory disease with unknown aetiology. Since various functions of neutrophils are increased in AS, neutrophil activation-mediated oxidative stress may have an important role in the pathogenesis of AS. Therefore, the importance of neutrophil activation as the main source of oxidative stress was investigated in patients with AS. METHODS: Forty-one patients with AS, divided into active and inactive groups according to their CRP and ESR, and 30 healthy volunteers were entered into the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the visual analogue scale (VAS) were also used in all patients before the study. In addition, the patients were evaluated according to spinal involvement and peripheral involvement. Plasma myeloperoxidase (MPO) activity, representing neutrophil activation, and oxidative stress biomarkers, such as advanced oxidation protein products (AOPP) and thiol levels, were measured. RESULTS: There were significant increases in plasma MPO activity and AOPP but decreases in thiol levels in the total AS patient group and in the subgroups, compared with controls. All parameters, except thiol, were higher in active and peripheral involvement groups than in the inactive and spinal patients, respectively; but the highest levels were observed in the peripheral subgroup. In addition, AOPP was found to be positively correlated with ESR, CRP and BASDAI in the total patient group and with white blood cell and neutrophil count in the peripheral involvement subgroup. BASDAI was positively correlated with VAS, ESR and CRP; but MPO was negatively correlated with thiol/albumin ratio, both in total and active AS patients. Negative correlations were also observed between albumin and ESR, and between CRP and neutrophil counts in the peripheral subgroup. CONCLUSIONS: This is the first study suggesting neutrophil-MPO-hypochlorous acid-mediated AOPP formation in AS. Therefore, active neutrophils and chlorinated oxidants of neutrophil origin may be considered to be important factors in the pathogenesis of AS which are related to oxidative stress, notably protein oxidation.
OBJECTIVES:Ankylosing spondylitis (AS) is a chronic inflammatory disease with unknown aetiology. Since various functions of neutrophils are increased in AS, neutrophil activation-mediated oxidative stress may have an important role in the pathogenesis of AS. Therefore, the importance of neutrophil activation as the main source of oxidative stress was investigated in patients with AS. METHODS: Forty-one patients with AS, divided into active and inactive groups according to their CRP and ESR, and 30 healthy volunteers were entered into the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the visual analogue scale (VAS) were also used in all patients before the study. In addition, the patients were evaluated according to spinal involvement and peripheral involvement. Plasma myeloperoxidase (MPO) activity, representing neutrophil activation, and oxidative stress biomarkers, such as advanced oxidation protein products (AOPP) and thiol levels, were measured. RESULTS: There were significant increases in plasma MPO activity and AOPP but decreases in thiol levels in the total AS patient group and in the subgroups, compared with controls. All parameters, except thiol, were higher in active and peripheral involvement groups than in the inactive and spinal patients, respectively; but the highest levels were observed in the peripheral subgroup. In addition, AOPP was found to be positively correlated with ESR, CRP and BASDAI in the total patient group and with white blood cell and neutrophil count in the peripheral involvement subgroup. BASDAI was positively correlated with VAS, ESR and CRP; but MPO was negatively correlated with thiol/albumin ratio, both in total and active AS patients. Negative correlations were also observed between albumin and ESR, and between CRP and neutrophil counts in the peripheral subgroup. CONCLUSIONS: This is the first study suggesting neutrophil-MPO-hypochlorous acid-mediated AOPP formation in AS. Therefore, active neutrophils and chlorinated oxidants of neutrophil origin may be considered to be important factors in the pathogenesis of AS which are related to oxidative stress, notably protein oxidation.
Authors: Derek L Mattey; Jonathan C Packham; Nicola B Nixon; Lucy Coates; Paul Creamer; Sarah Hailwood; Gordon J Taylor; Ashok K Bhalla Journal: Arthritis Res Ther Date: 2012-05-28 Impact factor: 5.156