Session Information
Session Title: Rheumatoid Arthritis - Clinical Aspects: Novel Biomarkers and Other Measurements of Disease Activity
Session Type: Abstract Submissions (ACR)
Background/Purpose
Monitoring disease activity in patients with autoimmune rheumatic disease is an essential part of clinical care. Highly reactive malondialdehyde (MDA) arise from reactive oxygen species and lipid peroxidation and can covalently modify proteins and increased levels of MDA may be associated with the inherent autoimmune pathogenic process. We therefore hypothesized that levels of IgG-autoantibodies to MDA-modified proteins may reflect core disease activity.
Methods
In the current study, serum IgG anti-MDA levels were compared in 71 healthy controls, 30 OA, and 15 PsA, 283 SLE and 162 RA patients identified by ACR criteria. IgG anti-MDA was measured by sandwich ELISA using MDA-modified BSA. Statistical differences were assessed by Mann-Whitney test and Spearman analysis.
Results
Compared to controls (5±3 RU/ml), IgG anti-MDA was significantly increased in patients with PsA (7.4±4 RU/ml, p=0.01), SLE (17±21 RU/ml, p<0.0001) and RA (13±11 RU/ml, p<0.0001). In SLE patients, IgG anti-MDA significantly correlated with the disease activity assessed by SELENA-SLEDAI (p<0.0001, R=0.34, n=219) and levels were higher in SLE patients with active disease (SLEDAI≥6, 18.9±17.3 RU/ml, p=0.001) than with low disease activity (SLEDAI>6, 11.5±16.6). In RA, IgG anti-MDA was significantly higher in new onset RA (<6 mo, 21±13 RU/ml, p<0.0001) than in chronic RA (>2 yr, 10±8 RU/ml). Notably, new onset RA patients had more active disease by DAS28 (5.7±1.2, p=0.01) than chronic RA patients generally on therapy (4.8±1.5). Importantly, IgG anti-MDA significantly correlated with DAS28-ESR (p<0.0001, R=0.35, n=157; with 16 seroneg), and compared to RA patients with more controlled disease (DAS28<3.2, 6±3) the levels were higher in moderate disease (DAS28 3.2-5.1, 12±11 RU/ml, p=0.005) and further elevated in active disease (DAS28>5.1, 15±12 RU/ml, p=0.001). IgG anti-MDA also correlated with TNFα (p=0.002, R=0.39), IL-6 (p=0.03, R=0.27), and CRP levels (p=0.003, R=0.37) in DMARD naïve RA patients (n=62).
Conclusion
IgG autoantibodies to MDA-modified determinants may provide a biomarker for disease activity in rheumatic autoimmune diseases. These autoantibodies could therefore provide a valuable early objective metric for diagnosis and for assessing disease activity. The potential mechanisms responsible for induction of IgG anti-MDA autoantibodies during the pathogenesis of systemic inflammation merits further study.
Disclosure:
C. Grönwall,
None;
L. Getu,
None;
J. D. Greenberg,
None;
R. M. Clancy,
None;
G. J. Silverman,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/levels-of-igg-autoantibodies-to-oxidation-associated-mda-neo-determinants-are-a-biomarker-for-systemic-inflammation-and-disease-activity-in-sle-and-ra/