Session Type: Abstract Submissions (ACR)
Background/Purpose: Type I interferon (IFN-I) has been implicated in SLE pathogenesis, and cross-sectional studies have shown that IFN-I pathway activation is associated with multiple disease manifestations. To identify those clinical and laboratory features most significantly associated with high IFN-I activity, we retrospectively evaluated IFN-I in plasma samples collected longitudinally from SLE patients.
Methods: Plasma samples as well as clinical and laboratory patient data were collected longitudinally from 60 patients meeting ACR criteria for SLE. On average, 9 visits (range 2-20) per patient and 568 data points were collected. WISH cells were stimulated with either recombinant IFN-I standard, healthy donor or SLE plasma for 5 hours. Quantification of biological response was performed by qPCR using IFIT1 as the target and HPRT1 as the reference gene. A linear mixed effect model was used to build regression models and correlate IFN-I activity of plasma across all patient visits with various clinical and laboratory parameters measured longitudinally. In total, 50 laboratory and clinical variables were analyzed.
Results: The longitudinal analysis identified that visits with high IFN-I activity correlated significantly with high disease activity determined by both SLEDAI (p<0.01) and BILAG scores (p<0.05). The rise in IFN-I activity often corresponded to lupus flares (p<0.05). Visits of SLE patients with hematologic (p<0.01), mucocutaneus (p<0.01) or vascular (p<0.05) activity (according to BILAG 2000 components) were associated with an increase in IFN-I levels. Among serologic parameters, a significant increase in antibody titer against dsDNA (p<0.01) and erythrocyte sedimentation rate (p<0.01) corresponded to higher IFN-I activity. Decreases in complement component 3 (p<0.01), white blood cell count (p<0.01), and absolute neutrophil count (p<0.01) were also associated with high IFN-I level.
Conclusion: The measurement of IFN-I activity in SLE patient plasma represents an important experimental parameter with possible clinical implications. The WISH assay, which measures the biological activity of IFN-I, was used to establish relationships between high interferon activity and multiple clinical manifestations in a longitudinal retrospective study. Our longitudinal analysis supports a significant association of high IFN-I activity with elevated disease activity, particularly in the mucocutaneous, vascular and hematologic systems.
W. T. Huang,
E. E. Jacek,
K. A. Kirou,
M. K. Crow,
Johnson and Johnson,
EMD Merck Serono,
Human Genome Sciences/GSK,
« Back to 2013 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/sle-disease-activity-in-the-mucocutaneus-vascular-and-hematologic-systems-is-associated-with-an-increase-in-plasma-type-i-interferon-activity/