伴或不伴自身免疫性疾病的胸腺瘤中自身免疫调节因子的表达

Autoimmune regulator expression in thymomas with or without autoimmune disease.

作者信息

Liu Yimei, Zhang Hui, Zhang Peng, Meng Fanjie, Chen Yuan, Wang Yuanguo, Yao Yuanyuan, Qi Bin

机构信息

Department of Cardiothoracic Surgery General Hospital at Tianjin Medical University, No. 154, Anshan Road, Heping District, Tianjin300052 PR China.

出版信息

Immunol Lett. 2014 Sep;161(1):50-6. doi: 10.1016/j.imlet.2014.04.008. Epub 2014 Apr 21.

DOI:10.1016/j.imlet.2014.04.008

PMID:24768600

Abstract

BACKGROUND

The autoimmune regulator (AIRE) regulates autoimmunity and self-antigen expression, such as acetylcholine receptor (AchR), in the thymus. Regulatory T cells (Tregs) can down-regulate autoimmunity, but also promote tumor growth. The objective of this study was to examine the levels of AIRE, AchR, and Foxp3 expression in thymomas.

METHODS

The relative levels of AIRE, AchR, and Foxp3 mRNA transcripts and the frequency of AIRE+, AchR+, and Foxp3+ cells were determined by quantitative RT-PCR and immunohistochemistry in 79 thymoma tissue samples from 21 patients with simple thymoma (the Tm group), 39 patients with myasthenia gravis (the MG group) and 19 patients with myasthenia gravis and one other autoimmune disease (the AD group). The numbers of peripheral blood CD4+CD25+Foxp3+ Tregs were determined by flow cytometry analysis.

RESULTS

The relative levels of AIRE and AchR mRNA transcripts in the MG group were significantly lower than that in the Tm group (p=0.04, p=0.03), but higher than that in the AD group (p=0.03, p=0.04). The relative levels of Foxp3 mRNA transcripts in the Tm group were significantly higher than that in the MG and AD groups (p=0.03 for both). A similar pattern of the percentages of AIRE+, AchR+, and Foxp3+ cells in the thymoma tissues and the numbers of peripheral blood Tregs were detected in these patients. The levels of AIRE mRNA transcripts were correlated positively with that of the AchR and Foxp3 in this population. The levels of AIRE and AchR mRNA transcripts in the A/AB/B1 types of thymomas were significantly higher than that in the B2/B3/C types of thymomas in this population.

CONCLUSION

Significantly lower levels of AIRE, AchR, and Foxp3 expression are associated with the development of thymoma-related autoimmune diseases.

摘要

背景

自身免疫调节因子（AIRE）在胸腺中调节自身免疫和自身抗原表达，如乙酰胆碱受体（AchR）。调节性T细胞（Tregs）可下调自身免疫，但也促进肿瘤生长。本研究的目的是检测胸腺瘤中AIRE、AchR和Foxp3的表达水平。

方法

采用定量逆转录聚合酶链反应（RT-PCR）和免疫组织化学方法，检测21例单纯胸腺瘤患者（Tm组）、39例重症肌无力患者（MG组）和19例重症肌无力合并另一种自身免疫性疾病患者（AD组）的79份胸腺瘤组织样本中AIRE、AchR和Foxp3 mRNA转录本的相对水平以及AIRE+、AchR+和Foxp3+细胞的频率。通过流式细胞术分析外周血CD4+CD25+Foxp3+ Tregs的数量。

结果

MG组中AIRE和AchR mRNA转录本的相对水平显著低于Tm组（p=0.04，p=0.03），但高于AD组（p=0.03，p=0.04）。Tm组中Foxp3 mRNA转录本的相对水平显著高于MG组和AD组（两者p均=0.03）。在这些患者中，检测到胸腺瘤组织中AIRE+、AchR+和Foxp3+细胞的百分比以及外周血Tregs数量的类似模式。该人群中AIRE mRNA转录本水平与AchR和Foxp3水平呈正相关。该人群中A/AB/B1型胸腺瘤的AIRE和AchR mRNA转录本水平显著高于B2/B3/C型胸腺瘤。