Background Systemic lupus erythematosus (SLE) is a complex, multifactorial autoimmune disease that affects multiple organ systems, including the kidney, skin, heart, lung, and hematopoietic and nervous systems. A hallmark of SLE is the production of high titers of autoantibodies against a broad spectrum of antigens. Given the broad spectrum of immune defects in SLE, it may be possible that autoantigens are generated by different pathogenic processes.
Objectives Broad autoantibody profiling in SLE may yield novel autoantibody targets for and may shed light on pathogenic pathways leading to the generation of autoantigens.
Methods 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 was 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 and Cohen's d effect size <0.3).
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 -38% in SLE. Interestingly, MVP is the major constituent of the vault particle, the largest known ribonuclear protein complex. Literature data suggest that vaults are involved in a diversity of cellular processes, including multidrug resistance, transport mechanisms, signal transmission, autophagy, immune and radiation response .
Conclusions MVP is a virus- and INFγ-induced and host factor, which up-regulates type I INF production . Although more studies are needed, our findings suggest a previously undescribed linkage of INF pathways and the generation of autoantigens.
Lara PC, Pruschy M, Zimmermann M, Henríquez-Hernández LA (2011). MVP and vaults: a role in the radiation response. Radiation Oncology (London, England). 6:148.
Liu S, Hao Q, Peng N, Yue X, Wang Y, Chen Y, Wu J, Zhu Y (2012). Major vault protein: a virus-induced host factor against viral replication through the induction of type-I interferon. Hepatology. 56(1):57–66.
Disclosure of Interest P. Budde Employee of: Protagen AG, S. Vordenbäumen: None declared, H.-D. Zucht Employee of: Protagen AG, P. Schulz-Knappe Employee of: Protagen AG, M. Schneider: None declared
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