Background Vaults are the largest nonicosahedral cytosolic ribonucleoprotein particles ever described, with a mass of 13Mda. They are ranging from 104 to 107 particles per cell, with an enormous interior volume, large enough to encapsulate hundreds of proteins or RNAs. Their functions have not been fully elucidated although various studies suggest that they are involved in multidrug resistance, nucleocytoplasmic transport, and intracellular signalling. Vaults are barrel-shaped particles comprising a 78-mer of major vault protein (MVP) molecules, 2 other proteins TEP1 and VPARP and a small untranslated RNA (vRNA). TEP1 shares sequence similarity with Ro autoantigen, a common target of autoantibodies, while vault RNA is complexed with another autoantigen the La protein. In this study, we sought to evaluate the levels of MVP in sera of patients with RA relative to healthy individuals.
Materials and methods MVP levels were quantified in serum of 46 patients with rheumatoid arthritis, 10 patients with early rheumatoid arthritis (ERA), 17 patients with osteoarthritis (OA) and 22 healthy individuals, using a MVP sandwich ELISA. We also measured the levels of RF, CRP and anti-CCP in the same serums.
Results MVP levels were found elevated in ERA (100% positive, 89.5% specificity) and RA (73.9% positive, 89.5% specificity), whereas the levels of MVP were found reduced in OA (17.6% positive) and normal subjects (4.5% positive). Notably, 50% of ERA patients were anti-CCP and RF negative and MVP positive. MVP levels were similar in RA and ERA patients but lower from OA patients and normal subjects (p<0.001). MVP levels were strongly correlated with the presence of anti-CCP antibodies (p<0.001) and RF (p<0.001) but not with CRP levels.
Conclusions MVP levels are remarkably elevated in both patients with RA or ERA, having the potential to serve as a new diagnostic marker for early detection of rheumatoid arthritis.