Monitoring disease activity in systemic lupus erythematosus with single-molecule array digital ELISA quantification of serum interferon-α.

OBJECTIVES: No simple or standardized assay is available to quantify interferon-α (IFNα) in routine clinical practice. Single-molecule-array (Simoa) digital enzyme-linked immunosorbent assay (ELISA) technology enables direct IFNα quantification at fg/mL concentrations. This study was undertaken to assess IFNα digital ELISA diagnostic performances to monitor systemic lupus erythematosus (SLE) activity.

METHODS: IFNα concentrations in serum samples from 150 consecutive SLE patients in a cross-sectional study were determined with digital ELISA and a functional biological activity assay (bioassay). According to their SELENA-SLEDAI flare composite, patients were divided into groups with inactive (SLEDAI <4 or clinical SLEDAI =0) or active SLE (SLEDAI ≥4 or clinical SLEDAI >0), and into groups with no flare or mild/moderate flare or severe flare.

RESULTS: Based on healthy blood donors, the abnormal serum-IFNα level threshold value was 136 fg/mL. Next, using receiver operating characteristics curves for an SLE-patient series, widely heterogeneous for disease activity and organ involvement, the threshold IFNα value associated with active disease was determined to be 266 fg/mL. The digital ELISA-assessed serum-IFNα level was a better biomarker of disease activity than the Farr test: its specificity, likelihood ratio for positive results and positive-predictive value better discerned active SLE or flare from inactive patients. The digital ELISA was more sensitive than the bioassay to detect low-abnormal serum-IFNα concentrations and patients with low disease activity.

CONCLUSION: Direct serum-IFNα determination with a highly sensitive assay might improve monitoring of clinical SLE activity and selection of the best candidates for anti-IFNα treatment. This article is protected by copyright. All rights reserved.