SAT0661 MXA IS A CLINICALLY APPLICABLE BIOMARKER FOR TYPE I INTERFERON ACTIVATION IN SYSTEMIC LUPUS ERYTHEMATOSUS AND SYSTEMIC SCLEROSIS

Abstract

Background Activation of the type I interferon (IFN) system has been found in large subsets of patients with systemic autoimmune diseases. This is usually assessed with a laborious quantification of IFN-stimulated genes. An easier and cheap biomarker would facilitate implementation of type I IFN measurements in diagnostic laboratories. Previously, we described Myxovirus resistance protein 1 enzyme immunoassay (MxA-EIA) for systemic evaluation of type I IFN activity in primary Sjogren’s syndrome [1]. Objectives To assess the applicability of the MxA-EIA to detect systemic type I IFN activation in patients with systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Methods Whole blood intracellular MxA protein levels were measured in SLE (discovery cohort: n=25; replication cohort retrieved from the CHILL-NL study [2]: n=102), SSc (n=28) and healthy controls (HC) using the MxA-EIA. IFN scores were determined from whole blood gene expression of interferon-stimulated genes IFI44, IFI44L, IFIT1, IFIT3, and MxA by RT-PCR. Results MxA levels were significantly elevated in patients with SLE and SSc compared to HC and highly correlated to IFN scores (rs=0.735 to rs=0.854, p≤0.003). MxA-EIA robustly discriminated (AUC=0.938 to AUC=0.991, p≤0.007) between low and high type I IFN activity in SLE and SSc patients with a specificity of 100% and a sensitivity of 87.5 to 94.7%. Patients with autoantibodies against SM, RNP, SSA/Ro, or SSB/La antigens showed higher MxA levels and IFN scores compared to patients without these antibodies. Conclusion Intracellular MxA is an easy applicable and clinically relevant biomarker for systemic type I IFN bioactivity in SLE and SSc. MxA-EIA could be used to identify patients eligible for IFN-targeting treatments and potentially to monitor treatment responses.