Session Type: Abstract Submissions (ACR)
Studies have shown that malondialdehyde-acetaldehyde (MAA) is formed as a result of lipid peroxidation of cellular membranes and is capable of binding or adducting to various macromolecules. MAA-adducted macromolecules are cytotoxic, proinflammatory and result in a robust specific adaptive immune response to the MAA structure. Previous studies have shown serum anti-MAA antibodies present in inflammatory diseases including; atherosclerosis, aortic aneurysm, alcoholic liver disease, and recently rheumatoid arthritis. The purpose of this study was to examine the potential utility of anti-MAA antibody isotypes as biomarkers in systemic lupus erythematosus (SLE). We also explored whether anti-MAA antibody isotypes were associated with two novel biomarkers that we have recently demonstrated to be increased in SLE, neutrophil extracellular traps (NETs) and NOD27/NLRC5.
Eighty-eight SLE patients, all satisfying ACR classification criteria, and 92 controls were examined. Serum antibody levels were measured by enzyme-linked immunosorbent assay (ELISA) for levels of IgG, IgA, and IgM specific to the MAA epitope. Spearman correlation coefficients were used to examine associations of MAA isotypes with NETs and NOD27/NLRC5.
MAA IgG concentration was significantly higher (p=0.004) in SLE patients (M=488.7 mg/L) compared to controls (M=331.7 mg/L) Figure 1. There was a strong trend (p=0.064) observed in MAA IgM concentrations between SLE samples (M=769.7 mg/L) and controls (M=586.7 mg/L). There was no difference observed between control and SLE groups for MAA IgA concentrations. Levels of MAA IgG demonstrated modest but statistically significant correlations with levels of NOD27/NLRC5 (r=.256, p=0.0508) and NB4 NET (r=.213, p=0.048) within the SLE group.
These data show that patients with SLE have significantly higher levels of MAA IgG and IgM compared to controls. In addition, MAA IgG concentrations were positively correlated with circulating levels of NB4 NETs and NOD27, consistent with the increased inflammatory burden that characterizes SLE. MAA has been shown to contribute to protein modifications eliciting strong immune responses and recruitment of proinflammatory cytokines. Whether MAA adduct formation and resulting immune responses mediate tolerance loss in SLE, as has been shown in other conditions, or other complications of SLE such as premature atherosclerosis warrants further investigation.
Figure 1. Serum samples were assayed by ELISA for the presence of IgG anti-MAA antibodies.
T. R. Mikuls,
G. M. Thiele,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/antibody-to-malondialdehyde-acetaldehyde-adducts-maa-as-a-potential-biomarker-of-inflammation-in-systemic-lupus-erythrematosus-sle/