Session Type: Abstract Submissions (ACR)
Background/Purpose: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder with a marked increase in cardiovascular (CV) morbidity and mortality due to premature atherosclerosis, distinct from what is predicted by the Framingham risk equation alone. This risk may be increased in pediatric-onset SLE (pSLE) due to the younger age of disease onset, greater disease severity, and longer disease burden seen in pSLE. Type I interferon (IFN) levels are elevated in SLE and have been shown to play a prominent role in premature vascular damage in adult patients and in animal models of SLE. We hypothesized that serum type I IFN activity may also be an independent predictor of subclinical atherosclerosis and endothelial dysfunction in pSLE.
Methods: A cross-sectional analysis of a pSLE cohort was performed. The following markers of subclinical atherosclerosis and endothelial dysfunction were measured in 132 pSLE patients and 138 healthy controls using standardized protocols: carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD) of the brachial artery, and aortic pulse wave velocity (PWV). Serum samples from the pSLE patients were assayed to quantify type I IFN serum activity, using a previously validated bioassay in which HeLa cells were incubated in the presence of pSLE or age- and gender-matched healthy control sera. HeLa RNA was then isolated and real-time quantitative PCR was performed to quantify the expression of 5 type I IFN-inducible genes (MX1, C1orf-29, IFIT1, PRKR, and IFI44) and the housekeeping gene HPRT1. Principal component analysis was used to establish the association between individual type I IFN-inducible genes and markers of subclinical atherosclerosis and endothelial dysfunction.
Results: Females accounted for 89% of pSLE patients; mean age was 14.8 ± 2.7 years. Disease duration at time of vascular tests was 2.1 ± 2.1 years, with a wide range spanning 2 months to 13.25 years. Mean CIMT was 0.41 ± 0.05 mm, mean FMD was 8.2% ± 3.94%, and mean aortic PWV was 5.45 ± 1.0 m/s. These results did not differ from the healthy control population. Four type I IFN-inducible genes were found to be significantly elevated in pSLE patients when compared with controls: MX1 (8-fold higher), C1orf-29 (3-fold higher), PRKR (2-fold higher), and IFI44 (2-fold higher). There was no correlation between type I IFN serum activity and markers of subclinical atherosclerosis and endothelial dysfunction in pSLE patients.
Conclusion: Serum type I IFN activity is increased in pSLE patients, but we found no association between serum type I IFN activity and markers of subclinical atherosclerosis and endothelial dysfunction in pSLE. These results are in contrast to the association which has been shown in adult SLE patients. Further study including longitudinal assessments is needed to evaluate if change in type I IFN activity over the duration of disease predicts progression of atherosclerosis and/or development of CV events in pSLE.
T. J. Bradley,
D. M. Levy,
E. D. Silverman,
M. J. Kaplan,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/type-i-interferons-as-a-serum-biomarker-of-subclinical-atherosclerosis-in-pediatric-systemic-lupus-erythematosus-patients/