Session Title: Rheumatoid Arthritis-Clinical Aspects III: Outcome Measures, Socioeconomy, Screening, Biomarkers in Rheumatoid Arthritis
Session Type: Abstract Submissions (ACR)
Background/Purpose: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with rheumatoid arthritis (RA). While there are many markers used for evaluating the development and/or progression of CVD, the recent use of pro-inflammatory macromolecules (CRP, IL-6, TNF-α) has become increasingly helpful in the diagnosis and evaluation of CVD. Our laboratory has been evaluating antibody isotypes and concentrations to a unique malondialdehyde (MAA) adduct that appear to correlate with both systemic inflammation and cardiovascular events. We have hypothesized that inflammation directed against MAA could serve as a link between systemic inflammation and the excess CVD burden that both characterize RA. Thus, as a first step in addressing our overarching hypothesis, we sought to evaluate whether associations existed between anti-MAA antibodies and measures of RA disease activity and severity.
Methods: Serum samples from 704 RA patients from the Veterans Affairs RA (VARA) registry were evaluated for the presence and concentration of IgM, IgA and IgG antibodies to the MAA epitope using ELISA. Associations of these antibody concentrations with traditional markers of RA (RF, ESR, CRP, ACPA, DAS28, etc.) were performed using non-parametric Spearman Rank Correlation statistics. Additionally, antibody isotype concentrations to MAA were compared for patients with radiographic bone erosions to those without erosions using a two-sample t-test.
Results: Statistically significant correlations were observed between anti-MAA antibody concentrations and multiple RA measures (Table) including RF isotypes, ACPA, ESR, and CRP. Isotype variability was observed with measures including RF (by nephelometry) and swollen joint count, while no associations were observed between anti-MAA concentrations and tender joints, MD-HAQ, and DAS28. Finally, patients with radiographic erosions demonstrated higher concentrations of IgA anti-MAA compared to patients without erosions (p = 0.043), a difference that was not observed for IgG or IgM anti-MAA isotypes.
Conclusion: These results show there is a relationship between anti-MAA antibody levels and several traditional measures of disease activity and/or severity in RA. Although we have previously shown that both MAA and anti-MAA may play a role in CVD pathogenesis in patients without RA, further investigation will be needed to better elucidate whether MAA-related inflammation could serve as a mechanistic link between RA and CVD burden.
M. J. Duryee,
L. A. Davis,
C. D. Hunter,
L. W. Klassen,
J. R. O’Dell,
T. R. Mikuls,
Roche/Genentech and Biogen IDEC Inc.,
G. M. Thiele,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/antibody-to-malondialdehyde-acetaldehyde-adducts-maa-is-a-biomarker-of-inflammation-and-is-correlated-with-the-disease-activity-in-rheumatoid-arthritis/