Elevated Levels of Soluble ST2 were Associated with Rheumatoid Arthritis Disease Activity and Ameliorated Inflammation in Synovial Fibroblasts.

Lian-jie Shi; Chen Liu; Jian-hong LI; Xiao-yun Zhu; Ying-ni LI; Jiang-tao LI

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Elevated Levels of Soluble ST2 were Associated with Rheumatoid Arthritis Disease Activity and Ameliorated Inflammation in Synovial Fibroblasts.

Author: Lian-Jie SHI ^{1
,

2
,

3} ; Chen LIU ⁴ ; Jian-Hong LI ⁵ ; Xiao-Yun ZHU ⁶ ; Ying-Ni LI ⁷ ; Jiang-Tao LI ⁸
Author Information

1. Department of Rheumatology and Immunology, Peking University International Hospital
2. Department of Rheumatology and Immunology, Peking University People's Hospital and Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135)
3. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
4. Department of Orthopaedics, Peking University International Hospital, Beijing 102206, China.
5. Department of Nuclear Medicine, Peking University International Hospital, Beijing 102206, China.
6. Department of Pathology, Peking University International Hospital, Beijing 102206, China.
7. Department of Rheumatology and Immunology, Peking University People's Hospital and Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing 100044, China.
8. Department of Rheumatology and Immunology, The First People's Hospital of Yibin, Yibin, Sichuan 644000, China.
Publication Type:Journal Article
From: Chinese Medical Journal 2018;131(3):316-322
CountryChina
Language:English
Abstract:
BACKGROUNDMuch evidence has demonstrated that interleukin (IL)-33 plays an important role in rheumatoid arthritis (RA). However, there have been limited studies about soluble ST2, a receptor for IL-33, in RA. The aims of this study were to detect the levels of ST2 in the serum and synovial fluid of RA patients and to reveal the association of these levels with disease activity and the function of ST2 in RA.
METHODSA total of 56 RA patients and 38 age-matched healthy controls were enrolled in this study. Synovial fluid samples were collected from another 30 RA patients and 20 osteoarthritis patients. Serum and synovial fluid levels of ST2 were measured by ELISA. In addition, the levels of ST2 in the serum of RA patients before and after therapy were detected. The function of ST2 in RA was revealed by the results of an in vitro cell assay, where recombinant ST2 proteins were used to treat peripheral blood mononuclear cells (PBMCs) and RA synovial fibroblasts (RASFs).
RESULTSSerum-soluble ST2 levels were significantly higher in RA patients (127.14 ± 61.43 pg/ml) than those in healthy controls (78.37 ± 41.93 pg/ml, P < 0.01). Synovial fluid-soluble ST2 levels (41.90 ± 33.58 pg/ml) were much higher in RA patients than those in osteoarthritis patients (19.71 ± 16.72 pg/ml, P < 0.05). RA patients who received effective therapy for 6 months showed decreased serum-soluble ST2 levels (113.01 ± 53.90 pg/ml) compared to baseline (139.59 ± 68.36 pg/ml) (P = 0.01). RA patients with high disease activity had higher serum-soluble ST2 levels (162.02 ± 56.78 pg/ml) than those with low disease activity (94.67 ± 40.27 pg/ml, P = 0.001). Soluble ST2 did not affect IL-1β, IL-6, IL-8, or tumor necrosis factor-α (TNF-α) expression in PBMCs from RA patients. However, soluble ST2 ameliorated the expressions of IL-33 and IL-1β but not that of IL-6, IL-8, or TNF-α in resting RASFs. Interestingly, in the RASFs stimulated by TNF-α plus IL-1β, soluble ST2 showed extensive suppressive effects on the expression of IL-6, IL-8, and TNF-α.
CONCLUSIONElevated levels of ST2 in the serum and synovial fluid were associated with disease activity and ameliorated IL-33 expression and IL-33-induced inflammation in RASFs, suggesting that soluble ST2 might be a potential therapeutic candidate for RA.