State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China.
J Clin Immunol. 2013 Apr;33(3):577-85. doi: 10.1007/s10875-012-9848-z. Epub 2012 Dec 14.
To evaluate the telomere/telomerase system and its clinical significance in immune thrombocytopenia (ITP) patients.
A total of 237 ITP patients, 20 SLE patients and 200 age-and sex-matched healthy controls were included in this study. CD4(+), CD8(+) and CD19(+) lymphocytes were purified by magnetic beads sorting from peripheral blood of 37 active chronic ITP patients and 22 age-and sex-matched healthy controls. Telomerase activity was assayed by Telo TTAGGG Telomerase PCR ELISA KIT. The relative telomere length of peripheral blood mononuclear cell (PBMC) was measured by a quantitative polymerase chain reaction-based method (Q-PCR) from 200 ITP patients and 178 age-and sex-matched healthy controls.
Telomerase activity was increased in CD4(+), CD8(+) and CD19(+) lymphocytes from ITP patients compared to those from healthy controls (p = 0.000). The level of telomerase activity in CD19(+) lymphocyte was higher than those in CD4(+) and CD8(+) lymphocytes. Telomerase activity of CD19+ lymphocytes had a modest negative correlation with platelet count in ITP patients (p = 0.042). The relative telomere length of PBMC in ITP patients was significantly shorter than that in the healthy controls (p = 0.002). Telomere length of PBMC in active ITP patients was significantly shorter than that in the controls (p = 0.000) and a tendency to be shorter even in inactive ITP patients (p = 0.065). Moreover, the telomere length in refractory and non-refractory ITP patients were both significantly shorter than that in the controls (p = 0.025; p = 0.000). However no significant difference in telomere length of PBMC was found between refractory ITP patients and non-refractory ITP patients (p = 0.234).
An abnormal regulating telomere/telomerase system might be involved in the pathogenesis of ITP. Further studies may elucidate whether the telomere length could be considered as a predictive biomarker for the prognosis of ITP.
评估端粒/端粒酶系统及其在免疫性血小板减少症(ITP)患者中的临床意义。
本研究纳入了 237 例 ITP 患者、20 例系统性红斑狼疮(SLE)患者和 200 名年龄和性别匹配的健康对照者。通过磁珠分选从 37 例活动性慢性 ITP 患者和 22 名年龄和性别匹配的健康对照者的外周血中纯化 CD4(+)、CD8(+)和 CD19(+)淋巴细胞。采用 Telo TTAGGG 端粒酶 PCR ELISA KIT 测定端粒酶活性。通过定量聚合酶链反应(Q-PCR)法从 200 例 ITP 患者和 178 名年龄和性别匹配的健康对照者中测量外周血单个核细胞(PBMC)的相对端粒长度。
与健康对照者相比,ITP 患者的 CD4(+)、CD8(+)和 CD19(+)淋巴细胞中端粒酶活性升高(p=0.000)。CD19(+)淋巴细胞中端粒酶活性高于 CD4(+)和 CD8(+)淋巴细胞。ITP 患者 CD19+淋巴细胞中端粒酶活性与血小板计数呈负相关(p=0.042)。ITP 患者的 PBMC 相对端粒长度明显短于健康对照者(p=0.002)。活动性 ITP 患者的 PBMC 端粒长度明显短于对照组(p=0.000),即使在非活动性 ITP 患者中也有缩短的趋势(p=0.065)。此外,难治性和非难治性 ITP 患者的 PBMC 端粒长度均明显短于对照组(p=0.025;p=0.000)。然而,难治性 ITP 患者和非难治性 ITP 患者的 PBMC 端粒长度无显著差异(p=0.234)。
异常调节的端粒/端粒酶系统可能参与了 ITP 的发病机制。进一步的研究可能阐明端粒长度是否可以作为 ITP 预后的预测生物标志物。