%A Enocsson,Helena %A Wetterö,Jonas %A Eloranta,Maija-Leena %A Gullstrand,Birgitta %A Svanberg,Cecilia %A Larsson,Marie %A Bengtsson,Anders A. %A Rönnblom,Lars %A Sjöwall,Christopher %D 2021 %J Frontiers in Immunology %C %F %G English %K SLE,lupus,biomarker,disease activity,interferon,chemokine,galectin,TNF %Q %R 10.3389/fimmu.2021.688753 %W %L %M %P %7 %8 2021-June-30 %9 Original Research %+ Helena Enocsson,Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linköping University,Sweden,helena.enocsson@liu.se %# %! Surrogate biomarkers of IFN-α in SLE %* %< %T Comparison of Surrogate Markers of the Type I Interferon Response and Their Ability to Mirror Disease Activity in Systemic Lupus Erythematosus %U https://www.frontiersin.org/articles/10.3389/fimmu.2021.688753 %V 12 %0 JOURNAL ARTICLE %@ 1664-3224 %X 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.