A recent groundbreaking study has highlighted the potential of a novel interferon gamma release assay as a powerful biomarker for assessing disease activity and predicting treatment response in patients with systemic lupus erythematosus (SLE).
Cytokines are key mediators of immune regulation, and their role in autoimmune diseases such as SLE is well recognized. In lupus, the overproduction of autoantibodies triggers an inflammatory cascade, leading to excessive cytokine release. Variations in disease activity, whether active or quiescent, affect levels of several cytokines, including interleukin 6, interleukin 4, interleukin 17, and interferon gamma. Elevated interferon gamma levels, in particular, have been linked to heightened disease activity.
The interferon system, comprising types I, II, and III interferons, plays a central role in both infection control and autoimmune pathogenesis. These interferons differ in their cellular sources, receptor targets, and immunological effects. While type I interferons such as interferon alpha and interferon beta are primarily associated with early lupus pathogenesis, type III interferons are key in viral defense, and type II interferon (interferon gamma) is crucial for intracellular pathogen control. Notably, interferon alpha has been implicated in the onset of lupus, whereas interferon lambda may reflect disease progression.
Building on this understanding, researchers have now repurposed interferon gamma release assays, originally designed for detecting Mycobacterium tuberculosis infection, to evaluate their utility in autoimmune conditions like lupus.
In the new retrospective study, investigators analyzed data from 145 lupus patients treated at a tertiary care center between 2008 and 2024. Both spontaneous and phytohemagglutinin (PHA) induced interferon gamma levels were measured, with the latter calculated after subtracting baseline values.
The results revealed distinct cytokine patterns: patients with active lupus showed significantly higher spontaneous interferon gamma release, while PHA induced interferon gamma responses were markedly reduced, independent of glucocorticoid or immunosuppressive use. Reduced PHA induced responses were consistently observed in patients with multi organ involvement, including lupus nephritis, serositis, and musculoskeletal or mucocutaneous manifestations.
Importantly, the PHA induced assay demonstrated superior performance in distinguishing clinically inactive disease. A threshold value of 8.0 IU/ml or higher accurately predicted remission, with an odds ratio of 10.6, while levels below 1.6 IU/ml were completely specific for active disease and correlated with delayed remission.
According to the authors, PHA induced interferon gamma release assessed at the time of therapy initiation or escalation could serve as a robust biomarker, helping clinicians not only identify active lupus but also predict treatment response during follow up. If validated in larger, prospective cohorts, this assay could represent a significant step forward in precision monitoring of lupus activity and tailoring of immunosuppressive therapy.
References
- Renaudineau Y, Treiner E, Herin F, Faguer S, Pugnet G, Sailler L. Interferon-γ release assay as an emergent powerful biomarker in systemic lupus erythematosus. Rheumatology (Oxford). 2025 Oct 1;64(10):5313-5321.
- Maharani W, Ratnaningsih DF, Utami F, Yulianto FA, Dewina A, Hamijoyo L, Atik N. Activity Disease in SLE Patients Affected IFN-γ in the IGRA Results. J Inflamm Res. 2020 Aug 14;13:433-439.