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

Objectives To investigate the ex vivo IFN-γ release assay (IGRA) as a biomarker of SLE activity and disease outcome. Methods This retrospective study, conducted between 2008 and 2024 at a single tertiary care center, 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< 1 0 −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 (AUC= 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 = 9.7x10−6), and IGRA-PHA ≤1.6 IU/ml was associated with a longer time to achieve remission in a log-rank test (p = 2.4x10−6). 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.