Comparison of Surrogate Markers of the Type I Interferon Response and Their Ability to Mirror Disease Activity in Systemic Lupus Erythematosus

Abstract

ObjectivesType I interferons (IFNs) are central and reflective of disease activity in systemic lupus erythematosus (SLE). However, IFN-α levels are notoriously difficult to measure and the type I IFN gene signature (IGS) is not yet available in clinical routine. This study evaluates galectin-9 and an array of chemokines/cytokines in their potential as surrogate markers of type I IFN and/or SLE disease activity.MethodsHealthy controls and well-characterized Swedish SLE patients from two cross-sectional cohorts (n=181; n=59) were included, and a subgroup (n=21) was longitudinally followed. Chemokine/cytokine responses in immune complex triggered IFN-α activity was studied in healthy donor peripheral blood mononuclear cells (PBMC). Levels of chemokines/cytokines and galectin-9 were measured by immunoassays. Gene expression was quantified by qPCR.ResultsThe IGS was significantly (p<0.01) correlated with galectin-9 (rho=0.54) and CXCL10 (rho=0.37) levels whereas serum IFN-α correlated with galectin-9 (rho=0.36), CXCL10 (rho=0.39), CCL19 (rho=0.26) and CCL2 (rho=0.19). The strongest correlation was observed between galectin-9 and TNF (rho=0.56). IFN-α and disease activity (SLEDAI-2K) were correlated (rho=0.20) at cross-sectional analysis, but no significant associations were found between SLEDAI-2K and galectin-9 or chemokines. Several inflammatory mediators increased at disease exacerbation although CCL19, CXCL11, CXCL10, IL-10 and IL-1 receptor antagonist were most pronounced. Immune complex-stimulation of PBMC increased the production of CCL2, CXCL8 and TNF.ConclusionGalectin-9 and CXCL10 were associated with type I IFN in SLE but correlated stronger with TNF. None of the investigated biomarkers showed a convincing association with disease activity, although CXCL10 and CCL19 performed best in this regard.

Tensor decomposition reveals coordinated multicellular patterns of transcriptional variation that distinguish and stratify disease individuals

“…The connection between higher ISG expression and these clinical features has been previously shown in several studies (Hooks et al, 1979; Bennett et al, 2003; Kirou et al, 2005; Nikpour et al, 2008; Weckerle et al, 2011). The Pearson correlation between factor 1 sample scores and SLEDAI was 0.321, which is similar to that which was observed in other studies (Catalina et al, 2019; Enocsson et al, 2021; Juárez-Vicuña et al, 2021).…”

MDA5 signaling induces type 1 IFN- and IL-1-dependent lung vascular permeability which protects mice from opportunistic fungal infection

“…As expected, pICLC induced robust IFN-β/α responses ( Figures 2A, B and Supplemental Figure 4 ) which were detectable above background after 2 hours, peaked after one day, then returned to baseline after seven days. CXCL10 is a t1IFN-induced chemokine ( 27 ) and its expression was also quite consistent with t1IFN ( Figures 2A, E ). In contrast, IL-28 (IFN-λ) was barely observed ( Figure 2A and Supplemental Figure 4 ).…”

Identification and analysis of the predictive urinary exosomal miR-195-5p in lupus nephritis based on renal miRNA-mRNA co-expression network

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