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.

---

« 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/