大动脉炎患者T细胞受体β链的分布初探  

Preliminary study on the distribution of T cell receptorβchain in patients with Takayasu arteritis

作　　者：高娜[1] 查博文 潘丽丽[1] Gao Na;Zha Bowen;Pan Lili(Department of Rheumatology,Capital Medical University Affiliated Anzhen Hospital,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院风湿免疫科,北京100029

出　　处：《中华风湿病学杂志》2023年第1期17-21,I0004,共6页Chinese Journal of Rheumatology

基　　金：北京市自然科学基金(7222043)。

摘　　要：目的探讨大动脉炎患者T细胞受体库的多样性,并分析T细胞受体β链基因表达及V、J基因重排的分布特点。方法采取8例大动脉炎患者和4名健康对照者的外周血,构建文库后,用Illumina Hiseq X10测序仪进行高通量测序。生物信息学分析所得序列,并与参考序列进行比对,统计V/D/J基因的频率信息,提取互补决定区(CDR)区域序列。评估免疫组库的多样性,进行样本间及样本内对比分析和聚类分析。应用R语言统计学软件分析数据。采用Mann-Whitney U检验。结果大动脉炎组和健康对照组β链第三互补决定区(CDR3)的D50指数和香农熵差异均无统计学意义。大动脉炎组和健康对照组的高频率克隆差异均无统计学意义。2组共有21个基因重排片段存在差异。其中TRBV15-TRBJ2-3[0.31(0.27,0.70)]、TRBV26-TRBJ2-6[0.30(0.23,0.57)]、TRBV28-TRBJ1-4[179(139,412)],TRBV28-TRBJ1-6[362(253,419)]等14个V/J基因重排片段在患者组中表达显著高于对照组(Z值分别为2.65,2.08,2.27,2.27,2.27,2.08,2.65,2.08,2.27,2.27,2.08,2.08,2.46,2.22,P值均<0.05);而TRBV10-1-TRBJ1-2[7.49(4.9,12.1)]、TRBV29-1-TRBJ2-2[10.5(4.0,12.8)],TRBV-4-2-TRBJ2-6[3.31(1.8,5.8)]等7个V/J基因重排片段在患者组中表达显著低于对照组(Z值分别为-2.08,-2.27,-2.08,-2.08,-2.27,-2.08,-2.29,P值均<0.05)。结论虽然大动脉炎患者外周血T细胞受体库无显著降低的多样性,但大动脉炎患者T细胞受体β链V、J基因表达存在差异,并且有独特的V/J重排亚家族。Objective To investigate the diversity of T cell receptor repertoire in patients with Takayasu arteritis and analyze the side chain gene expression and distribution pattern of V、J gene rearrangement of T cell receptors.Methods The peripheral blood samples of 8 patients with Takayasu arteritis and 4 healthy controls were collected.After constructing the library,high-throughput sequencing was performed with Illumina hiseq X10 sequencer.Bioinformatics analysis was conducted to obtain the sequences and compared with the reference sequences.the frequency information of V/D/J genes,and extraction of CDR region sequenceswere compared.The diversity of the TCR repertoire was also evaluated,and the comparative analysis and cluster analysis between groups and within samples were carried out.The data were analyzed by R language statistical software.Comparisons between two groups were analyzed by Mann-Whitney U test.Results There was no significant difference in D50 index and Shannon entropy of chain CDR3 between Takayasu arteritis group and healthy control group.There was no significant difference in high-frequency cloning between the two groups.However,a total of 21 gene rearrangement fragments were different between the two groups.The expression of 14 V/J gene rearrangement fragments such as TRBV15-TRBJ2-3[0.31(0.27,0.70)],TRBV26-TRBJ2-6[0.30(0.23,0.57)],TRBV28-TRBJ1-4[179(139,412)],TRBV28-TRBJ1-6[362(253,419)]in the patient group was significantly higher than that in the control group(Z score were 2.65,2.08,2.27,2.27,2.27,2.08,2.65,2.08,2.27,2.27,2.08,2.08,2.46 and 2.22 respectively,P<0.05).The expression of seven V/J gene rearrangement fragments such as TRBV10-1-TRBJ1-2[7.49(4.9,12.1)],TRBV29-1-TRBJ2-2[10.5(4.0,12.8)],TRBV-4-2-TRBJ2-6[3.31(1.8,5.8)]in the patients with Takayasu arteritis group was significantly lower than that in the control group(Z score were-2.08,-2.27,-2.08,-2.08,-2.27,-2.08 and-2.29,P<0.05).Conclusion Although there is no significant decrease in the diversity of peripheral blood TCR repertoire in p

关 键 词：TAKAYASU动脉炎 受体 抗原 T细胞 互补决定区 V(D)J重组 

分 类 号：R543.5[医药卫生—心血管疾病]