AB0684 Role of interleukin-33/ST2 pathway in sjÖgren's syndrome. (23rd January 2014)

• Record Type: Journal Article
• Authors: Navarini, L.; Margiotta, D.P.E.; Vadacca, M.; Maresca, B.; Vernuccio, A.; Afeltra, A.
• Is Part Of: Annals of the rheumatic diseases. Volume 71(2012)Supplement 3
• Page Start: 677
• Page End: 677
• Publication Date: 2014-01-23
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2012-eular.684
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Interleukin-33 (IL-33) is a member of IL-1 superfamily and seems to be produced by endothelium and epithelial cells of exocrine glands, including salivary glands. IL-33 mediates its biological effects by interacting with its receptor ST2, which exists in transmembrane (ST2L) and soluble (sST2) form. In culture, this cytokine induces the production of IL-5 and IL-13, but not of IL-4, by Th2 lymphocytes; in vivo, it also seems to mediate the secrection of IFNg by Th1 lymphocytes. Moreover, it is implicated in remodeling of connective tissue and fibrosis process. Several studies demonstrated the immunopathogenetic role in Allergic Asthma, RCU, Crohn disease, RA, Systemic Lupus Erythematosus (SLE) and Systemic Sclerosis. Objectives: To investigate the role of IL-33/ST2 in Sjögren's Syndrome (SS), compared with two control populations: SLE patients and healty subjects. Methods: 29 patients with SS, 19 with SLE (control group 1) and 20 healty subjects (control group 2) were enrolled from outpatients of Campus Bio-Medico University. All patients were subjected to clinical interview concerning activity, disease and drug history and they were evaluated for laboratory data (kidney and hepatic function, complete blood count, coagulation, complement fraction, immunoglobulins, CRP, ESR) and autoantibodies (ANA, ENA, SSA, SSB, anti-dsDNA, Sm, ReumaTest, Waaler-Rose). Disease activity and damage indexes were assessed at time of enrollment in this study with the use of SLEDAI and SLICC for SLE and SSDAI and SSDDI for SS, respectively. IL-33 and sST2 serum levels were determined by sandwich ELISA (Human IL-33 DuoSet, R&Systems, and Human ST2/IL-1R4 Quantikine ELISA kit, R&D systems). Results: sST2 serum levels were significantly increased in SS and SLE patients compared with healthy controls (p=0.03 and p=0.04 respectively). No signficant difference was found in sST2 levels in SS and SLE patients. In SS population, a negative correlation between sST2 levels and hemoglobin values (p=0.001) and a positive one between sST2 levels and prednisone daily dose (p=0.04) were found. In SLE population, a positive correlation between sST2 levels and ESR (p=0.004) and RCP (p=0.002) were found. IL-33 serum levels were detectable in a few subjects (9/29 SS, 6/19 SLE, 4/20 healthy subjects), not correlated with sST2 levels. In SS population, a positive correlation between IL-33 and IgA levels (p=0.003), WBC count (p=0.008) and ANA positivity (p=0.04) was found; also in SLE population, a positive correlation between IL-33 levels and WBC count (p=0.008) was found. Conclusions: Our data allow to hypothesize an implication of IL-33/ST2 pathway in immunopathogenesis of SS, peculiarly in active inflammation, as suggested by the relations with WBC count, IgA levels and the inverse correlation with hemoglobin values. Similarly to other studies, we detected IL-33 levels only in few subjects; this finding could be explained either by formation of receptor-cytokine complexes or by a negative feedback mechanism between IL-33 and ST2. References: Schmitz J, Owyang A, Oldham E 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;23:479-90. Mok MY, Huang FP, Ip WK et al. Serum levels of IL-33 and soluble ST2 and their association with disease activity in systemic lupus erythematosus. Rheumatology (Oxford) 2010;49:520-7. Disclosure of Interest: None Declared