Matsuda Takehiro, Tomita Mariko, Uchihara Jun-Nosuke, Okudaira Taeko, Ohshiro Kazuiku, Tomoyose Takeaki, Ikema Tomoki, Masuda Masato, Saito Mineki, Osame Mitsuhiro, Takasu Nobuyuki, Ohta Takao, Mori Naoki
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan.
J Clin Endocrinol Metab. 2005 Oct;90(10):5704-10. doi: 10.1210/jc.2005-0679. Epub 2005 Aug 2.
Autoimmune thyroid diseases have been reported to be associated with human T cell leukemia virus type I (HTLV-I) infection. HTLV-I proviral load is related to the development of HTLV-I-associated myelopathy/tropical spastic paraparesis and has also been shown to be elevated in the peripheral blood of HTLV-I-infected patients with uveitis, arthritis, and connective tissue disease.
The objective of the study was to evaluate the proviral load in HTLV-I-infected patients with Hashimoto's thyroiditis (HT) or Graves' disease (GD) and ascertain the ability of HTLV-I to infect thyroid cells.
A quantitative real-time PCR assay was developed to measure the proviral load of HTLV-I in peripheral blood mononuclear cells from 26 HTLV-I-infected patients with HT, eight HTLV-I-infected patients with GD, or 38 asymptomatic HTLV-I carriers. Rat FRTL-5 thyroid cells were cocultured with HTLV-I-infected T cell line MT-2 or uninfected T cell line CCRF-CEM. After coculture with T cell lines, changes in Tax and cytokine mRNA expression were studied by RT-PCR.
HTLV-I proviral load was significantly higher in the peripheral blood of patients with HT and GD than asymptomatic HTLV-I carriers. In the peripheral blood from HTLV-I-infected patients with HT, HTLV-I proviral load did not correlate with the thyroid peroxidase antibody or thyroglobulin antibody titer. After coculture with MT-2 cells, FRTL-5 cells expressed HTLV-I-specific Tax mRNA. These cocultured FRTL-5 cells with MT-2 cells expressed IL-6 mRNA and proliferated more actively than those cocultured with CCRF-CEM cells.
Our findings suggest the role of the retrovirus in the development of autoimmune thyroid diseases in HTLV-I-infected patients.
据报道,自身免疫性甲状腺疾病与人类I型嗜T细胞病毒(HTLV-I)感染有关。HTLV-I前病毒载量与HTLV-I相关脊髓病/热带痉挛性截瘫的发生有关,并且在患有葡萄膜炎、关节炎和结缔组织病的HTLV-I感染患者的外周血中也显示升高。
本研究的目的是评估HTLV-I感染的桥本甲状腺炎(HT)或格雷夫斯病(GD)患者的前病毒载量,并确定HTLV-I感染甲状腺细胞的能力。
开发了一种定量实时PCR检测方法,以测量26例HTLV-I感染的HT患者、8例HTLV-I感染的GD患者或38例无症状HTLV-I携带者外周血单个核细胞中HTLV-I的前病毒载量。将大鼠FRTL-5甲状腺细胞与HTLV-I感染的T细胞系MT-2或未感染的T细胞系CCRF-CEM共培养。与T细胞系共培养后,通过RT-PCR研究Tax和细胞因子mRNA表达的变化。
HT和GD患者外周血中的HTLV-I前病毒载量显著高于无症状HTLV-I携带者。在HTLV-I感染的HT患者的外周血中,HTLV-I前病毒载量与甲状腺过氧化物酶抗体或甲状腺球蛋白抗体滴度无关。与MT-2细胞共培养后,FRTL-5细胞表达HTLV-I特异性Tax mRNA。这些与MT-2细胞共培养的FRTL-5细胞表达IL-6 mRNA,并且比与CCRF-CEM细胞共培养的细胞增殖更活跃。
我们的研究结果表明逆转录病毒在HTLV-I感染患者自身免疫性甲状腺疾病发展中的作用。