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FRI0054 Elevated 14-3-3 eta in rheumatoid arthritis and arthritogenic viral infections
  1. O. S. Zhukov1,
  2. R. W. Abolhosn1,
  3. J. M. Popov1,
  4. S. J. Naides1
  1. 1Immunology, Quest Diagnostics Nichols Institute, San Juan Capistrano, United States

Abstract

Background The 14-3-3 proteins are ubiquitously-expressed intracellular chaperonins. Expression of the η (eta) isoform is restricted to synovial and CNS tissues.1 Extracellular 14-3-3η induces proinflammatory MAPK and NFkB cascades in THP-1 cells in vitro.2 Extracellular 14-3-3η has been proposed as a novel biomarker for joint damage in rheumatoid arthritis (RA) and psoriatic arthritis, with serum elevation occurring in early RA. 14-3-3η positivity may add diagnostic sensitivity to laboratory RA markers such as rheumatoid factor (RF) and citrullinated cyclic peptide antibody (CCP).3 However, 14-3-3η expression in arthritogenic viral infection has not been studied.

Objectives The aim of this study was to determine the frequency of elevated 14-3-3η in patients with RA and in those with HCV, acute EBV, or acute B19 infections.

Methods We have developed a quantitative 14-3-3η sandwich ELISA and verified the reference range using 134 serum specimens from healthy donors (67 males, 67 females; ages 18-65). 14-3-3η was measured in de-identified residual clinical specimens originally submitted for routine RA or infectious disease diagnostic testing.

Results The 14-3-3η 95th-percentile reference range was defined as <0.2 ng/ml and the reportable range was <0.2 to >20.0 ng/mL. Six healthy subjects (4%) had elevated 14-3-3η levels; 2 of them were weakly RF positive. RF+/CCP+ subjects had the highest frequency of elevated 14-3-3η (56%) and the highest 14-3-3η median level (Table). Frequency of elevated 14-3-3η was lower in the RF+/CCP- and virus-infected groups and was comparable among the groups. None of the RF-/CCP+ subjects had elevated 14-3-3η, but the number of subjects was small (n=10). Frequency of elevated 14-3-3η in the RF-/CCP- group was 5%. Of 23 subjects with elevated 14-3-3η in the HCV group, 1 was RF+/CCP+, 13 RF+/CCP-, and 9 RF-/CCP-. Of 6 subjects with elevated 14-3-3η in the EBV group, 1 was RF+/CCP+, 2 RF+/CCP-, and 3 RF-/CCP+. All 5 subjects with elevated 14-3-3η in the B19 group were RF-/CCP-.

Conclusions 14-3-3η elevation was most frequent among patients with RF+/CCP+ results (consistent with an RA diagnosis). 14-3-3η elevation also occurred less frequently in the RF+/CCP-, RF-/CCP-, HCV, EBV, and B19 groups. The data suggest that RA and some HCV, EBV, and parvovirus B19 infections may share pathogenetic mechanisms characterized by synovial release of 14-3-3η. Of note, the median abnormal 14-3-3η level was higher in the RF+/CCP+ group than in the virus-infected groups, suggesting less synovitis in viral arthritis than in RA, which is consistent with clinical observations.

References

  1. Kilani et al. J Rheum 34:1650-7, 2007.

  2. Marotta A. Arth Rheum 63 suppl 10: 1836, 2011

  3. Maksymowych et al. Arth Rheum 64 suppl 10:977, 2012.

Disclosure of Interest O. Zhukov Employee of: Quest Diagnostics Nichols Institute, R. Abolhosn Employee of: Quest Diagnostics Nichols Institute, J. Popov Employee of: Quest Diagnostics Nichols Institute, S. Naides: None Declared

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