In patients with systemic lupus erythematosus (SLE), elevated serum interferon (IFN)-α levels and IFN type I (IFN-I) gene scores have been shown to perform equally in the assessment of disease activity, according to the study results published in Annals of the Rheumatic Diseases.

In the current cross-sectional study, gene expression was evaluated using messenger RNA (mRNA) profiling by the NanoString nCounter gene expression system, and serum IFN-α and IFN-γ were quantified using digital enzyme-linked immunosorbent assay (ELISA) technology.

The researchers sought to explore whether IFN-I gene scores in the blood and IFN-α or IFN-γ levels quantified by digital ELISA in the serum exhibited a similar performance as biomarkers, mirroring the clinical activity of SLE. Researchers also studied the contribution of IFN-α and IFN-γ to the expression levels of different IFN-stimulated genes (ISGs) and IFN-I gene score.


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A total of 133 Swiss patients with SLE were enrolled in the current study. The median participant age was 45.6 years (range, 19.0-78.8 years); 111 (83%) of the patients were women; and 98 (75%) were White.

Overall, 75 (56%) of the total participants had active disease, determined by clinical Systemic Lupus Erythematosus Disease Activity Index (cSLEDAI); the contribution of low serum complement and elevated antidouble-stranded DNA (dsDNA) autoantibodies with a cutoff of greater than 0 to define active disease were excluded from the analysis.

Based on the predefined cutoffs, the prevalence of high IFN-I gene scores, elevated IFN-α serum levels, and elevated IFN-γ serum levels were 44% (n=58), 45% (n=60), and 14% (n=18), respectively. Serum IFN-α levels exhibited a highly positive association with IFN-I gene scores (Spearman’s correlation coefficient: rho=0.82), as well as with the expression level of individual ISGs (other than CXCL10). However, serum IFN-γ levels exhibited a weak positive association with IFN-I gene scores (rho=0.32) and IFN-α serum levels (rho=0.35), as well as with the expression level of individual ISG (except for CXCL10 that demonstrated a stronger positive association [rho=0.60] in accordance with a preferential induction of CXCL10 by IFN-γ). 

According to Cohen’s kappa coefficient, IFN-α serum levels exhibited a significant agreement to classify SLE as having high or low IFN-I gene scores (κ=0.72; 95% CI, 0.60-0.84); however, the agreement was low for IFN-γ. The sensitivity, specificity, negative predictive value, and positive predictive value of serum IFN-α levels to classify SLE as having high or low IFN-I gene scores were 86%, 87%, 89%, and 83%, respectively.

Further, both elevated IFN-α serum levels and IFN-I gene scores were associated with active SLE, as defined by cSLEDAI of greater than 0 or a SLEDAI of 4 or more.

According to multivariable analysis, both elevated IFN-α serum levels and IFN-I gene scores were associated with active skin lesions, arthritis, and positive anti-dsDNA autoantibodies. Conversely, IFN-γ was not associated with active SLE or with active SLE disease characteristics.

IFN-I gene score area under the curve (AUC) was 0.63 (95% CI, 0.53-0.72) and serum IFN-α AUC was 0.63 (95% CI, 0.53-0.72) both performed similarly and significantly better than C3 levels (AUC, 0.42 [95% CI, 0.32-0.52]) for differentiating inactive vs active SLE (adjusted P =.03 for both).

This is the first time researchers have indicated that IFN-α, evaluated by digital ELISA, and IFN-I gene score perform equally in identifying the association of IFN-I with SLE disease activity and clinical manifestations of the disease.

Study limitations included the cross-sectional design and the small sample size.

The researchers concluded that additional studies are warranted to explore why IFN-γ serum levels do not perform optimally as SLE biomarkers.

Reference

Chasset F, Mathian A, Dorgham K, et al. Serum interferon-α levels and IFN type I-stimulated genes score perform equally to assess systemic lupus erythematosus disease activity. Ann Rheum Dis. Letter. Published online January 28, 2022. doi:10.1136/annrheumdis-2021-221835