骨髓单个核细胞抗人球蛋白试验阳性的血细胞减少症患者Th17细胞数量及功能的研究

[Study of the quantity and function of Th17 cells in the blood cytopenic patients with positive BMMNC-Coombs test].

作者信息

Fu Rong, Wang Hong-Lei, Chen Jin, Wang Jun, Li Li-Juan, Liu Hui, Wang Yi-Hao, Ren Yue, Shao Zong-Hong

机构信息

Department of Hematology, General Hospital, Tianjin Medical University, Tianjin 300052, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2010 Oct;31(10):684-7.

PMID:21223720

Abstract

OBJECTIVE

To study the quantity and function of bone marrow (BM) Th17 cells in the blood cytopenia patients with positive BMMNC-Coombs test (IRP) and to explore the role of Th17 cells in the pathogenesis of the disease.

METHODS

Forty-three untreated IRP patients, 34 recovered IRP patients and 13 healthy donors were enrolled in this study. The ratio of IL-23R(+)CD4(+)/CD4(+)cells in BM were examined by flow cytometry(FCM), the levels of IL-6, IL-23, IL-17 by ELISA, and the expressions of RORγt mRNA, STAT3 mRNA in BMMNC by semiquantitive RT-PCR.

RESULTS

The ratio of IL-23R(+)CD4(+)/CD4(+)cells [(3.6 ± 3.1)%], the levels of IL-6[(26.21 ± 14.55) µg/L], IL-23[(2.23 ± 0.99) µg/L], IL-17[(2.54 ± 1.33) µg/L] and the expressions of RORγt mRNA (0.25 ± 0.08) and STAT3 mRNA (1.10 ± 0.16) in BMMNC of untreated IRP patients were significantly higher than those of recovered IRP patients[(2.0 ± 1.0)%, (9.08 ± 6.36) µg/L, (0.91 ± 0.76) µg/L, (1.28 ± 0.18) µg/L, 0.12 ± 0.08, 0.97 ± 0.12 respectively] (P < 0.05); there was no significiant difference between those of recovered IRP patients and normal controls [(1.9 ± 1.4)%, (14.63 ± 7.66) µg/L, (1.19 ± 0.98) µg/L, (1.50 ± 0.28) µg/L, 0.07 ± 0.05, 0.95 ± 0.13, respectively] (P > 0.05). In IRP group, there were significantly positive correlations between the ratios of IL-23R(+)CD4(+)/CD4(+)cells and CD5(+)CD19(+)/CD19(+) (P < 0.05), there were significantly positive correlations between the levels of IL-17 and CD5(+)CD19(+)/CD19(+), the quantity of BMMNC-antibody (r = 0.494 and 0.377, respectively) (P < 0.05); and so did between the expressions of RORγt mRNA and the ratio of CD5(+)CD19(+)/CD19(+), the quantity of BMMNC-antibody (r = 0.741 and 0.541, respectively) (P < 0.05), and between the ratio of IL-23R(+)CD4(+)/CD4(+) and the level of IL-17, the expression of STAT3 mRNA (r = 0.438 and 0.448, respectively) (P < 0.05).

CONCLUSIONS

There exists increased qunantity and hyperfunction of Th17 cells in the IRP patients which induce B cells hyperfunction and production of autoantibodies against the BM hematopoietic cells. Th17 cells might be a potential new therapeutic target of IRP.

摘要

目的

研究骨髓单个核细胞抗人球蛋白试验（IRP）阳性的血细胞减少症患者骨髓（BM）Th17细胞的数量及功能，探讨Th17细胞在该疾病发病机制中的作用。

方法

本研究纳入43例未经治疗的IRP患者、34例病情缓解的IRP患者和13名健康供者。采用流式细胞术（FCM）检测骨髓中IL-23R(+)CD4(+)/CD4(+)细胞的比例，酶联免疫吸附测定（ELISA）检测IL-6、IL-23、IL-17水平，半定量逆转录聚合酶链反应（RT-PCR）检测骨髓单个核细胞（BMMNC）中RORγt mRNA、STAT3 mRNA的表达。

结果

未经治疗的IRP患者骨髓中IL-23R(+)CD4(+)/CD4(+)细胞比例[（3.6±3.1）%]、IL-6水平[（26.21±14.55）μg/L]、IL-23水平[（2.23±0.99）μg/L]、IL-17水平[（2.54±1.33）μg/L]以及RORγt mRNA表达（0.25±0.08）和STAT3 mRNA表达（1.10±0.16）均显著高于病情缓解的IRP患者[分别为（2.0±1.0）%、（9.08±6.36）μg/L、（0.91±0.76）μg/L、（1.28±0.18）μg/L、0.12±0.08、0.97±0.12]（P<0.05）；病情缓解的IRP患者与正常对照组之间无显著差异[分别为（1.9±1.4）%、（14.63±7.66）μg/L、（1.19±0.98）μg/L、（1.50±0.28）μg/L、0.07±0.05、0.95±0.13]（P>0.05）。在IRP组中，IL-23R(+)CD4(+)/CD4(+)细胞比例与CD5(+)CD19(+)/CD19(+)之间存在显著正相关（P<0.05），IL-17水平与CD5(+)CD19(+)/CD19(+)、BMMNC抗体量之间存在显著正相关（r分别为0.494和0.377）（P<0.05）；RORγt mRNA表达与CD5(+)CD19(+)/CD19(+)比例、BMMNC抗体量之间也存在显著正相关（r分别为0.741和0.541）（P<0.05），IL-23R(+)CD4(+)/CD4(+)比例与IL-17水平、STAT3 mRNA表达之间也存在显著正相关（r分别为0.438和0.448）（P<0.05）。