Autoimmune regulator expression in thymomas with or without autoimmune disease.
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.


CONCLUSIONS
Significantly lower levels of AIRE, AchR, and Foxp3 expression are associated with the development of thymoma-related autoimmune diseases.
Department of Cardiothoracic Surgery General Hospital at Tianjin Medical University, No. 154, Anshan Road, Heping District, Tianjin300052 PR China.
Yimei
Y
Liu
Department of Cardiothoracic Surgery General Hospital at Tianjin Medical University, No. 154, Anshan Road, Heping District, Tianjin300052 PR China.
Hui
H
Zhang
Department of Cardiothoracic Surgery General Hospital at Tianjin Medical University, No. 154, Anshan Road, Heping District, Tianjin300052 PR China. Electronic address: zhp-gh@hotmail.com.
Peng
P
Zhang
Department of Cardiothoracic Surgery General Hospital at Tianjin Medical University, No. 154, Anshan Road, Heping District, Tianjin300052 PR China.
Fanjie
F
Meng
Department of Cardiothoracic Surgery General Hospital at Tianjin Medical University, No. 154, Anshan Road, Heping District, Tianjin300052 PR China.
Yuan
Y
Chen
Department of Cardiothoracic Surgery General Hospital at Tianjin Medical University, No. 154, Anshan Road, Heping District, Tianjin300052 PR China.
Yuanguo
Y
Wang
Department of Cardiothoracic Surgery General Hospital at Tianjin Medical University, No. 154, Anshan Road, Heping District, Tianjin300052 PR China.
Yuanyuan
Y
Yao
Department of Cardiothoracic Surgery General Hospital at Tianjin Medical University, No. 154, Anshan Road, Heping District, Tianjin300052 PR China.
Bin
B
Qi
D000954:Antigens, Surface / Q000378:metabolism; D001327:Autoimmune Diseases / Q000150:complications*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013945:Thymoma / Q000150:complications* / Q000235:genetics* / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000096927:AIRE Protein
D000954:Antigens, Surface; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D014157:Transcription Factors; D000096927:AIRE Protein; C418974:FOXP3 protein, human
Acetylcholine receptor; Autoimmune abnormality; Autoimmune regulator; Helix/forkhead transcription factor; Thymoma