Interferon-γ release assay as an emergent powerful biomarker in systemic lupus erythematosus

Abstract

Objectives: To investigate the ex vivo IFN-γ release assay (IGRA) as a biomarker of systemic lupus erythematosus (SLE) activity and disease outcome.

Methods: This retrospective study, conducted between 2008 and 2024 at a single tertiary care centre, included 145 SLE patients at various disease stages. Data were collected on spontaneous IFN-γ levels (IGRA-nil) and on phytohemagglutinin-induced IFN-γ levels (IGRA-PHA, after subtracting the IGRA-nil result).

Results: The ex vivo spontaneous IFN-γ release was increased (IGRA-nil; P = 0.0004) and the PHA-induced IFN-γ release was decreased in active SLE patients (IGRA-PHA; P < 10-4), regardless of treatment, including glucocorticoids. Nephritis, serositis, constitutional symptoms, mucocutaneous and musculoskeletal manifestations were associated with impaired IGRA-PHA release (P < 0.05 for each association). An IGRA-PHA ≥ 8.0 IU/ml, corresponding to the optimal Youden index, predicted clinically inactive SLE better than IGRA-nil (area under the curve = 0.853 vs 0.722) and IGRA-PHA <1.6 IU/ml indicated 100% specificity for active disease. Moreover, IGRA-PHA ≥ 8.0 IU/ml was an independent predictor of clinically inactive SLE in multivariate regression analysis (OR: 10.6 [95% CI: 3.72-30.17]; P = 9.7 × 10-6), and IGRA-PHA ≤1.6 IU/ml was associated with a longer time to achieve remission in a log-rank test (P = 2.4 × 10-6).

Conclusion: The IGRA-PHA assay appears to be a powerful and independent biomarker for clinically active SLE, when performed at the initiation or intensification of therapy, and as a predictor of treatment-induced remission at therapy evaluation.

Keywords: biomarker; disease activity; interferon-gamma; interferon-gamma release assay; phytohemagglutinin; remission; systemic lupus erythematosus.