原发性干燥综合征患者的白细胞介素33/ST2轴：在血清和唾液腺中的表达及其临床关联
The Interleukin 33/ST2 axis in patients with primary Sjögren syndrome: expression in serum and salivary glands, and the clinical association.
作者信息
Jung Seung Min, Lee Jaeseon, Baek Seung Ye, Lee Jae Ho, Lee Jennifer, Park Kyung-Su, Park Sung-Hwan, Kim Ho-Youn, Kwok Seung-Ki
机构信息
From the Division of Rheumatology, Department of Internal Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital; the Rheumatism Research Center, Catholic Research Institute of Medical Science, Seoul, South Korea.SM. Jung, MD, Clinical Fellow; JH. Lee, MD, Clinical Fellow; J. Lee, MD, Clinical Assistant Professor; K-S. Park, MD, PhD, Professor; S-H. Park, MD, PhD, Professor; H-Y. Kim, MD, PhD, Professor; S-K. Kwok, MD, PhD, Associate Professor, Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, and the Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea; J. Lee, MS, Research Associate; S.Y. Baek, BA, Research Assistant, the Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea.
出版信息
J Rheumatol. 2015 Feb;42(2):264-71. doi: 10.3899/jrheum.140234. Epub 2014 Dec 15.
OBJECTIVE
To evaluate the expression of interleukin 33 (IL-33) and its receptor in sera and salivary tissues of patients with primary Sjögren syndrome (pSS), and to investigate the association with clinical profiles.
METHODS
Serum IL-33 and soluble ST2 (sST2) of 55 patients with pSS and 48 controls were determined by ELISA and assessed for clinical correlation. The expression of IL-33/ST2 in salivary tissues was investigated by immunohistochemical staining and was further characterized by confocal microscopy. We also measured IL-33 production in salivary glandular epithelial cells by proinflammatory stimuli.
RESULTS
Serum levels of IL-33 and sST2 were higher in patients with pSS compared to those in controls (p = 0.018 and p < 0.0001, respectively). Among patients with pSS, sST2 concentration was associated with thrombocytopenia (p = 0.029) and correlated with disease duration (p = 0.013) and the European League Against Rheumatism Sjögren Syndrome Disease Activity Index (p = 0.042). The expression of IL-33 and ST2 was elevated in salivary glands of patients with pSS with grade 2 inflammation, and diminished in advanced inflammation. In patients with pSS, IL-33 was mainly observed in epithelial and endothelial cells of glandular tissue. The production of IL-33 mRNA by salivary gland epithelial cell line increased under stimulation with interferon-γ.
CONCLUSION
The expression of IL-33 and its receptor was elevated in sera and salivary tissues of patients with pSS. These results suggest that the IL-33/ST2 axis might have a role in the pathogenesis of pSS.
目的
评估原发性干燥综合征（pSS）患者血清及唾液组织中白细胞介素33（IL-33）及其受体的表达，并探讨其与临床特征的相关性。
方法
采用酶联免疫吸附测定（ELISA）法检测55例pSS患者和48例对照者血清中的IL-33和可溶性ST2（sST2），并评估其临床相关性。通过免疫组织化学染色研究唾液组织中IL-33/ST2的表达，并采用共聚焦显微镜进一步分析其特征。我们还通过促炎刺激检测唾液腺上皮细胞中IL-33的产生。
结果
与对照组相比，pSS患者血清中IL-33和sST2水平更高（分别为p = 0.018和p < 0.0001）。在pSS患者中，sST2浓度与血小板减少症相关（p = 0.029），并与疾病持续时间（p = 0.013）和欧洲抗风湿病联盟干燥综合征疾病活动指数（p = 0.042）相关。pSS患者唾液腺中IL-33和ST2的表达在2级炎症时升高，在晚期炎症时降低。在pSS患者中，IL-33主要在腺组织的上皮细胞和内皮细胞中观察到。唾液腺上皮细胞系在干扰素-γ刺激下IL-33 mRNA的产生增加。
结论
pSS患者血清及唾液组织中IL-33及其受体的表达升高。这些结果表明，IL-33/ST2轴可能在pSS的发病机制中起作用。
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