Background/Purpose: In systemic lupus erythematosus (SLE), early diagnosis and prognostic stratification are still great challenges. The broad characterization of the autoantibody repertoire in SLE is an emerging tool to supporting a personalized disease management approach. We have recently conducted autoantibody profiling studies of SLE, systemic autoimmune diseases (AID), and healthy controls to identify biomarkers for improving lupus diagnosis and patient stratification. Here we describe the identification of autoantibodies against the major vault protein (MVP) in SLE and its subsequent development into an ELISA based assay.

Methods: A large-scale Luminex bead-based autoantibody screen was conducted by combining diagnostic with putative antigens. In the discovery phase the autoantibody reactivity of serum samples from 130 SLE patients, 794 AID patients (systemic sclerosis, rheumatoid arthritis/RA, early RA, ankylosing spondylitis) and 343 healthy controls were tested against 6,912 recombinant human proteins. Following validation in independent SLE samples (n=101), consistent autoantibody reactivity against 46 antigens was found (p-value <0.05). The newly discovered autoantigen was developed into a prototypical ELISA format and analyzed for diagnostic performance using a medium sized control cohort consisting of n=93 serum samples (24 healthy controls, 42 SLE, 14 SSc, and 13 Sjögren syndrome (SjS) serum samples).

Results: A data base search of 46 known and novel SLE-associated antigens revealed that the expression of ten proteins is upregulated by type I interferon (INF) (http://www.interferome.org). Beyond known antigens (TRIM21/Ro52, SSB), we identified a novel autoantibody target MVP with a frequency of 20 % in SLE. Initial findings of the Luminex based screening results were verified by the results of the ELISA test; the newly discovered MVP autoantigen revealed sensitivity and specificity of 26% and 98% respectively. Anti-MVP antibodies were also found in SLE patients tested negative for dsDNA, Sm, and Ribosomal P. Interestingly, MVP is the major constituent of the vault particle, which is a cytoplasmic organelle and the largest known ribonuclear protein complex. Although the exact biological function of MVP is not well understood, literature data suggest that MVP is a virus-induced host factor, which up-regulates type I INF production [1].

Conclusion: Anti-MVP autoantibodies represent a useful marker in SLE and, in combination with anti-dsDNA, anti-Sm and anti-ribosomal P, optimizes the strategy for autoantibody testing. Furthermore, although more studies are needed, our findings suggest a previously undescribed linkage of type I INF and autoantibody targets in SLE. Liu S et al. (2012). Hepatology. 56(1):57-66.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/discovery-and-subsequent-diagnostic-verification-of-autoantibodies-against-the-major-vault-protein-mvp-in-systemic-lupus-erythematosus/