Background/Purpose: Type I interferon (IFN-I) is elevated in many patients with SLE and is associated with more severe disease. However, the relationship between elevated levels of IFN-I and disease activity over time has not been defined. We evaluated the biological activity of IFN-I retrospectively in SLE plasma samples collected longitudinally from 60 SLE patients. The IFN-I activity in plasma was determined based on the response of the WISH cell line, which is sensitive to IFN-I stimulation and has a minimum detection level of 6 IU/ml.

Methods: Plasma samples as well as clinical and laboratory data were collected longitudinally. On average, 9 visits (range: 2-20 visits) per patient or 568 data points were collected. WISH cells were stimulated with either recombinant IFN-I standard, healthy donor or SLE plasma for 5 hours. The response of WISH cells was measured by quantitative PCR (qPCR) using interferon response gene IFIT1 as the target and HPRT1 as the reference gene. Patients were divided into two groups based on either low or high IFN-I activity at study initiation. Based on the collected data we built statistical models (linear mixed effect model and generalized linear model) using the level of plasma IFN-I activity at the first patient visit as a predictor of future clinical and laboratory outcomes.

 Results: SLE patients with high IFN-I plasma activity at study initiation showed increased IFN-I plasma activity during follow up visits (p<0.01). Among the laboratory parameters, the same patients had significant decreases in peripheral blood complement component 3 levels (p<0.03), white blood cell count (p<0.04), absolute lymphocyte count (p<0.01) and had higher erythrocyte sedimentation rate (p<0.02) and double stranded DNA titers (p<0.02). Patients with high plasma IFN-I activity during the first visit were prone to overall greater disease activity during the study as measured by SLEDAI (p<0.02) or BILAG (p<0.05). Strikingly, SLE patients with high IFN-I activity in plasma at study initiation were more likely (1.0 versus 0.4 incident per year p<0,001) to demonstrate renal BILAG activity.

Conclusion: Lupus nephritis is the most common severe manifestation of SLE and confers an increased risk of death and end-stage renal disease. In this study, we observed that IFN-I activity in SLE plasma could predict future disease activity, particularly involving the kidney. Furthermore, patients with higher plasma IFN-I activity at study initiation maintained elevated levels at future visits. Measurement of IFN-I activity in plasma of SLE patients may help identify patients at high risk for lupus nephritis and thus serve as an important disease monitoring biomarker.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/high-type-i-interferon-in-systemic-lupus-erythematosus-plasma-predicts-future-renal-disease/