267 Novel autoantibodies against the interferon-responsive major vault protein (mvp) in systemic lupus erythmatosus

Background and aims Autoantibody reactivity patterns are important disease and risk stratification marker in systemic lupus erythematosus (SLE). We have recently identified autoantibodies against the major vault protein (MVP) in SLE. Although the exact biological function of MVP is not well understood, MVP is an interesting autoantibody target, because it plays a pivotal role in virus-induced host response. MVP expression is induced by IFNγ and induces upregulation of interferon (IFN) type I expression. Methods Anti-MVP antibodies were discovered by high-content autoantibody profiling and validated in u003e700 SLE samples and autoimmune disease controls. To enable the development of smaller marker panels, we have developed anti-MVP into prototypic bead-based ELISA format. Results Discovery and validation experiments using the NavigAID SLE array showed that anti-MVP antibodies occurred with frequencies of 15%–30% in three different SLE cohorts at a specificity of 97%. Exploratory testing of multi-marker panels consisting of anti-MVP in combination with anti-dsDNA, anti-ribosomal P and anti-SmD yielded a 6% increase in sensitivity at 98% without loss of specificity. Multivariate data projection methods revealed that anti-MVP is detected in a subset of SLE patients with little overlap to established marker..A bead-based ELISA was developed for measuring anti-MVP antibodies and showed good correlation with Luminex data (R=0.88) indicating successful platform transfer. Conclusions Anti-MVP autoantibodies represent a useful marker in SLE and, in combination with established markers, optimises the strategy for autoantibody testing. Furthermore, although more studies are needed, our findings suggest a previously undescribed linkage of type I IFN and autoantibody targets in SLE.