Increased levels of serum protein oxidation and correlation with disease activity in systemic lupus erythematosus.
OBJECTIVE
To examine protein oxidation in systemic lupus erythematosus (SLE) and to correlate levels of protein oxidation products with disease activity.


METHODS
Serum was collected from SLE patients and healthy control subjects. Protein-bound carbonyls and the pro-oxidant enzyme myeloperoxidase (MPO) were quantified by enzyme-linked immunosorbent assay. Protein thiols were quantified using 5,5'-dithionitrobenzoic acid. Protein-bound amino acids and methionine, tyrosine, and phenylalanine oxidation products were quantified by acid hydrolysis and high-performance liquid chromatography. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Levels of anti-double-stranded DNA (anti-dsDNA) antibodies were measured by radioimmunoassay.


RESULTS
Compared with control subjects, SLE patients exhibited elevated levels of protein carbonyls (0.108 +/- 0.078 versus 0.064 +/- 0.028 nmoles/mg of protein; P = 0.046), decreased levels of protein thiols (3.9 +/- 1.1 versus 4.9 +/- 0.7 nmoles/mg of protein; P = 0.003), decreased levels of protein-bound methionine (P = 0.0007), and increased levels of protein-bound methionine sulfoxide (P = 0.0043) and 3-nitrotyrosine (P = 0.0477). SLE patients with high SLEDAI scores or elevated anti-dsDNA antibody levels exhibited increased oxidation compared with patients with low SLEDAI scores or low antibody levels. Serum MPO levels were decreased in SLE patients (P = 0.03), suggesting that this enzyme is not responsible for the enhanced protein oxidation.


CONCLUSIONS
We found elevated levels of multiple markers of protein oxidation in sera from SLE patients compared with controls, and these levels correlated with disease activity. The findings suggest that protein oxidation may play a role in the pathogenesis of chronic organ damage in SLE.
Free Radical Group, The Heart Research Institute, Camperdown, Sydney, New South Wales, Australia.
Philip E
PE
Morgan
Allan D
AD
Sturgess
Michael J
MJ
Davies
D000328:Adult; D000974:Antibodies, Antinuclear / Q000032:analysis / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000276:immunology; D005260:Female; D006304:Health Status; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D011485:Protein Binding; D011863:Radioimmunoassay; D012720:Severity of Illness Index; D013438:Sulfhydryl Compounds / Q000097:blood
D000974:Antibodies, Antinuclear; D015415:Biomarkers; D001798:Blood Proteins; D013438:Sulfhydryl Compounds; D004247:DNA; D009195:Peroxidase