Evidence for immune activation against oxidized lipoproteins in inactive phases of juvenile chronic arthritis.
OBJECTIVE
Oxidative stress contributes to joint inflammation and damage in rheumatoid arthritis. In a mobile inflamed joint, exercise induced multiple cycles of hypoxia-reperfusion injury may lead to the creation of a redox environment in which oxido-reductase systems, by NADPH mechanisms, produce highly reactive chemical species (i.e., oxygen free radicals). We investigated 2 endproducts of lipid peroxidation, malonildialdehyde (MDA) and diene conjugates (DC), and the formation of antibodies against oxidized low density lipoproteins (Ab oxLDL) in juvenile chronic arthritis (JCA), and assessed the role of oxidative phenomena in different phases and subsets of this disease.


METHODS
To assess the role of oxidative stress in JCA, we measured the endproducts of lipid peroxidation, MDA and DC, by the increase of absorbance at 586 nm and 234 nm, respectively, and the levels of Ab oxLDL by ELISA in the sera of 58 patients with JCA and 21 healthy controls. Due to crossreactivity between Ab oxLDL and anticardiolipin antibodies (aCL), the sera were also tested by a standard ELISA for IgG-aCL. The patients were divided into 3 subsets: 29 with pauciarticular (pauci), 15 with polyarticular (poly), and 14 with systemic (sys) onset disease, and then were subdivided, according to different variables appropriate to each subset, reflecting active and inactive disease, into 30 active (14 pauci, 8 poly, 8 sys) and 28 inactive (15 pauci, 7 poly, 6 sys).


RESULTS
Levels of Ab oxLDL were significantly increased in the whole group of patients (566.6 +/- 263.0 vs 206.6 +/- 136.3 mU/ml; p < 0.001) and in each of the type of onset (pauci 660.8 +/- 272.1, p < 0.001; poly 341.3 +/- 134.7, p < 0.01; sys 497.8 +/- 114.8, p < 0.001) compared to controls. Ab oxLDL were higher in the inactive than in the active group (743.5 +/- 231.9 and 404.4 +/- 169.9; p < 0.001). MDA and DC levels were not increased significantly in patients' sera. No patient was positive for IgG-aCL.


CONCLUSIONS
These findings suggest that MDA and DC cannot be considered major markers of oxidative stress in JCA and that the Ab oxLDL may represent a delayed sign of oxidative stress previously induced by the inflammatory process in patients with JCA.
Simonini
G
G
Department of Pediatrics, University of Florence, Italy.
Matucci Cerinic
M
M
Cimaz
R
R
Anichini
M
M
Cesaretti
S
S
Zoppi
M
M
Generini
S
S
Falcini
F
F
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008054:Lipid Peroxides / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008727:Methotrexate / Q000627:therapeutic use; D018384:Oxidative Stress / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D008315:Malondialdehyde; D008727:Methotrexate