SAT0661 MXA IS A CLINICALLY APPLICABLE BIOMARKER FOR TYPE I INTERFERON ACTIVATION IN SYSTEMIC LUPUS ERYTHEMATOSUS AND SYSTEMIC SCLEROSIS
Authors: Erika Huijser, C.G. van Helden-Meeuwsen, Noortje Groot, Iris LA Bodewes, M. Javad Wahadat, Marco Wj Schreurs, Paul LA van Daele, Virgil Ash Dalm, Jan van Laar, P Martin van Hagen, Matti Waris, Sylvia Kamphuis, Marjan Versnel
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> 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 Sjögren's syndrome [1]. <h3>Objectives</h3> 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). <h3>Methods</h3> 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. <h3>Results</h3> MxA levels were significantly elevated in patients with SLE and SSc compared to HC and highly correlated to IFN scores (r<sub>s</sub>=0.735 to r<sub>s</sub>=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. <h3>Conclusion</h3> 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. <h3>References</h3> [1] Maria NI, Brkic Z, Waris M, van Helden-Meeuwsen CG, Heezen K, van de Merwe JP, van Daele PL, Dalm VA, Drexhage HA, Versnel MA. MxA as a clinically applicable biomarker for identifying systemic interferon type I in primary Sjogren's syndrome. Ann Rheum Dis 2014;73:1052-9. [2] Groot N, Shaikhani D, Teng YKO, de Leeuw K, Bijl M, Dolhain R, Zirkzee E, Fritsch-Stork R, Bultink IEM, Kamphuis S. Long-term clinical outcomes in a cohort of adults with childhood-onset Systemic Lupus Erythematosus. Arthritis Rheumatol 2018; doi: 10.1002/art.40697. <h3>Acknowledgement</h3> The research for this manuscript was (partly) performed within the framework of the Academic Centers for Rare Immunological Diseases and Inflammunity, and the Erasmus Postgraduate School Molecular Medicine. <h3>Disclosure of Interests</h3> Erika Huijser: None declared, C.G. van Helden-Meeuwsen: None declared, Noortje Groot: None declared, Iris LA Bodewes: None declared, M. Javad Wahadat: None declared, Marco WJ Schreurs: None declared, Paul LA van Daele: None declared, Virgil ASH Dalm: None declared, Jan van Laar: None declared, P Martin van Hagen: None declared, Matti Waris: None declared, Sylvia Kamphuis: None declared, Marjan Versnel Grant/research support from: MAV received financial support from Domainex.