Short CommunicationPotential contribution of interleukin-33 to the development of interstitial lung disease in patients with primary Sjogren’s Syndrome☆
Introduction
Primary Sjogren’s Syndrome (pSS) is an inflammatory autoimmune disease that is characterized by lymphocytic infiltration of the exocrine glands resulting in xerostomia and keratoconjunctivitis sicca. The inflammatory process can affect extra glandular organs such as lung. The pathogenesis of the disease is still unclear and so no effective therapy is available. However, Th1/Th2 balance has been found to be impaired in pSS patients.
Interleukin (IL)-33, a new member of the IL-1 family [1], has been identified as the ligand of the orphan receptor ST2 [2]. IL-33 plays a key role in mediating Th2 immune response by activating nuclear factor-κB (NF–κB) and mitogen-activated protein kinase (MAPK) [3]. Furthermore, IL-33 can also induce the secretion of inflammatory mediators by mast cells [4]. ST2 is a member of the IL-1 receptor family and was discovered to be specific ligand of IL-33 [2]. There are three different splice variants of ST2: ST2L, soluble ST2 (sST2) and ST2V. IL-33 stimulates target cells by binding to ST2. sST2 acts as a decoy receptor that prevents the interaction of ST2L with IL-33.
Previous studies have shown that IL-33/sST2 may play an important role in autoimmune diseases such as rheumatoid arthritis (RA) [5], allergic rhinitis [6], and systemic lupus erythematosus (SLE) [7]. However, the roles of IL-33 and sST2 in pSS are unknown. In present study, we investigated the serum levels of IL-33/sST2 and association with clinical parameters in the patients with pSS.
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Patients
110 Untreated Chinese patients with pSS (106 females and 4 males, mean age 55.5 years) were recruited from the department of Rheumatology and Immunology, the First Affiliated Hospital of China Medical University. 78 healthy controls (HC) (75 females and 3 males, mean age 56.5 years), whose age and gender were matched to the patient cohort, were also recruited. The diagnosis of pSS was based on the American-European Consensus Group criteria [8]. The present study was approved by the Ethics
Clinical characteristics of pSS patients
Demographic and clinical characteristics of pSS patients are shown in Table 1.
Among these 110 patients, 81(73.6%) were RF-positive, 103(93.6%) were ANA-positive, 66(60.0%) were anti-SSA/Ro-52 antibody positive, 48(43.6%) were anti-SSB antibody positive and 54(49.1%) had ILD. (Table. 1).
Increased serum levels of IL-33 and sST-2 in pSS patients
Serum IL-33 levels were significantly higher in pSS patients than in healthy controls (pSS vs HC, median, [25–75percentiles], pg/ml: 54.4, [26.2–169.5] vs 24.1, [13.4–31.6], P < 0.001) (Fig. 1A). Furthermore, serum
Discussion
To our knowledge, this study is the first to show that serum levels of IL-33 were elevated in patients with pSS. IL-33 acts as a pro-inflammatory cytokine which can mediate various human autoimmune diseases. Our previous study showed elevated serum levels of IL-33 in RA patients, especially in RA patients with ILD [9]. However, the reports on relationship between IL-33 and the disease activity in RA and SLE were quite controversial. One study showed that IL-33 levels were elevated in sera from
Acknowledgments
All authors have no actual or potential conflicts of interest with other people or organizations within three years of initiating the work presented here. This work was supported by National Nature Science Foundation of China under Grant No. 81172867.
References (14)
- 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) - et al.
Soluble ST2 blocks interleukin-33 signaling in allergic airway inflammation
J Biol Chem
(2007) - et al.
Increased levels of interleukin-33 associated with bone erosion and interstitial lung diseases in patients with rheumatoid arthritis
Cytokine
(2012) - et al.
IL-1 receptor accessory protein and ST2 comprise the IL-33 receptor complex
J Immunol
(2007) - et al.
IL-33 induces IL-13 production by mouse mast cells independently of IgE-FcepsilonRI signals
J Leukocyte Biol
(2007) - et al.
Measurement of interleukin-33(IL-33) and IL-33 receptors (sST2 and ST2L) in patients with rheumatoid arthritis
J Korean Med Sci
(2011) - et al.
The role of IL-33 and its receptor ST2 in human nasal epithelium with allergic rhinitis
Clin Exp Allergy
(2012)