Peng Linyi, Ma Weizhi, Yi Fan, Yang Yun-Jiao, Lin Wei, Chen Hua, Zhang Xuan, Zhang Li-He, Zhang Fengchun, Du Quan
From the Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital; Chinese Academy of Medical Sciences and Peking Union Medical College; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.L. Peng, PhD, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education; W. Ma, BS; F. Yi, PhD, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University; Y-J. Yang, PhD; W. Lin, BS; H. Chen, PhD; X. Zhang, PhD, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education; L-H. Zhang, PhD, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University; F. Zhang, PhD, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education; Q. Du, PhD, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University.
J Rheumatol. 2014 Nov;41(11):2208-13. doi: 10.3899/jrheum.131154. Epub 2014 Aug 15.
Characterized by chronic inflammation, dysfunction of exocrine glands, and systemic autoimmunity, primary Sjögren syndrome (pSS) is a common autoimmune disease in elderly women. Our study was performed to explore the potential involvement of microRNA (miRNA) in Chinese patients with pSS.
Using microarrays, miRNA expression in peripheral blood mononuclear cells (PBMC) was profiled in 4 female patients with pSS and 3 healthy participants, followed by a large-scale study of 33 patients and 10 healthy individuals. Compared to the healthy participants, 202 miRNA were upregulated and 180 were downregulated in the patients with pSS. To confirm this finding, a set of regulated miRNA was further examined in a large patient group, using quantitative reverse transcriptase-PCR assays.
MiR-181a was the miRNA that most profoundly differed between patients with pSS and healthy individuals; however, similar miRNA-181a expression profiles were found in groups with different disease phenotypes. Together, these observations suggested that an elevated miRNA-181a level is a general phenomenon in Chinese patients with pSS.
In addition to the elevated miR-181a levels, our study led to the speculation that elevated miR-181a levels in the PBMC of these patients compromise the maturation of B cells, enabling them to recognize and attack autoantigens and resulting in disease phenotypes. In addition to the regulation of human miRNA, many virus-derived miRNA were unexpectedly upregulated in the patients with pSS, suggesting that viral infection of PBMC plays a role in this disease.
原发性干燥综合征(pSS)是老年女性常见的自身免疫性疾病,其特征为慢性炎症、外分泌腺功能障碍和全身自身免疫。我们开展本研究以探索微小RNA(miRNA)在中国pSS患者中的潜在作用。
使用微阵列技术分析了4例pSS女性患者和3名健康参与者外周血单个核细胞(PBMC)中的miRNA表达,随后对33例患者和10名健康个体进行了大规模研究。与健康参与者相比,pSS患者中有202种miRNA上调,180种miRNA下调。为证实这一发现,使用定量逆转录聚合酶链反应检测法在一个大型患者组中进一步检测了一组受调控的miRNA。
MiR-181a是pSS患者与健康个体之间差异最为显著的miRNA;然而,在不同疾病表型的组中发现了相似的miRNA-181a表达谱。这些观察结果共同表明,miRNA-181a水平升高是中国pSS患者中的普遍现象。
除了miR-181a水平升高外,我们的研究还推测,这些患者PBMC中miR-181a水平升高会损害B细胞的成熟,使其能够识别并攻击自身抗原,从而导致疾病表型。除了人类miRNA的调控外,许多病毒衍生的miRNA在pSS患者中意外上调,这表明PBMC的病毒感染在该疾病中起作用。