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THU0054 Interleukin-33/St2 Axis in Primary SjÖGren's Syndrome: Expression in Serum and Salivary Gland, and Clinical Association
  1. S.M. Jung1,
  2. J.Y. Kang1,
  3. H.K. Min1,
  4. J.H. Koh1,
  5. Y.S. Suh1,
  6. J.H. Lee1,
  7. J. Lee1,
  8. J.Y. Lee1,
  9. J.-M. Kim2,
  10. J.H. Ju1,
  11. K.-S. Park1,
  12. S.-H. Park1,
  13. H.-Y. Kim3,
  14. S.-K. Kwok1
  1. 1Internal Medicine, The Catholic University Of Korea, Seoul
  2. 2Internal Medicine, Keimyung University School of Medicine, Dongsan Medical Center, Daegu
  3. 3Internal Medicine, Konkuk University Hospital, School of Medicine, Seoul, Korea, Republic Of

Abstract

Background IL-33 and its receptor, ST2, are associated with many inflammatory disorders. However, the data on IL-33/ST2 in Sjögren's syndrome (SS) is very limited.

Objectives To evaluate the expression of IL-33 and its receptor in sera and salivary tissues obtained from patients with primary Sjögren's syndrome (pSS) and to investigate the possible relationship with clinical profiles.

Methods Serum IL-33 and soluble ST2 (sST2) of 55 patients with pSS and 48 controls were determined using ELISA, and assessed for correlation with clinical profiles. The expression of IL-33/ST2 in salivary tissues was investigated by immunohistochemical (IHC) staining, and was further characterized by confocal microscopy. We also measured ST2 expression in peripheral blood mononuclear cells (PBMCs) of pSS patients, and IL-33 production in salivary glandular epithelial cell by pro-inflammatory stimuli.

Results The serum levels of IL-33 and sST2 were higher in pSS patients compared to healthy controls (P=0.018 and P<0.0001, respectively). Among pSS patients, serum sST2 concentration was associated with thrombocytopenia (P=0.029) and duration of disease (p=0.013). Contrary to sST2, ST2 was downregulated in PBMCs obtained from pSS patients. The expression of IL-33 and ST2 was elevated in salivary gland of pSS patients with grade 2 inflammation, and decreased as inflammation progresses. In pSS patients, IL-33 was mainly observed in epithelial cells and endothelial cells of gland tissue. The production of IL-33 mRNA by salivary gland epithelial cell line was increased under stimulation with interferon-γ.

Conclusions IL-33 and sST2 concentrations were elevated in sera of pSS patients, whereas ST2 in salivary gland and PBMC of pSS patients showed downregulated expression. This result suggests that IL-33/ST2 axis might have a role in the pathogenesis of pSS.

References

  1. Schmitz, J., et al., IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity, 2005. 23(5): p. 479-90.

  2. Palmer, G. and C. Gabay, Interleukin-33 biology with potential insights into human diseases. Nat Rev Rheumatol, 2011. 7(6): p. 321-9.

  3. Moussion, C., N. Ortega, and J.P. Girard, The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel `'alarmin”? PLoS One, 2008. 3(10): p. e3331.

Acknowledgements This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI13C0016).

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.4921

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