Polymorphism of peripheral blood T cell receptor &beta; chain variable region in patients with clinically isolated syndrome

doi:10.3969/j.issn.1672-6731.2020.09.005

Abstract

Abstract:

Objective To investigate the polymorphism of T cell receptor β chain variable region (TCRVβ) in peripheral blood of clinically isoiated syndrome (CIS) patients. To preliminarily predict the specific TCRVβ fragment of CIS and its diagnostic value for CIS. Methods Hospitalized patients of Beijing Xuanwu Hospital from September 2012 to March 2014, were divided into 2 groups including CIS group (experimental pateints, n=30) and normal control group (healthy volunteers, n=30). The routine immune indexes and expression of TCRVβ subfamilies were detected by flow cytometry. CELL Quest Pro 5.1 software was used to analyze 24 subfamilies of TCRVβ. Calculated the statistic of amplification rate, amplification number and amplification fraction of the total 24 subfamilies of TCRVβ. Results Compared to the normal control group, the quantitative expression of CD4⁺ TCRVβ2, 4, 5.2, 5.3, 7.1, 8, 14, 17, 20, 21.3 and CD8⁺TCRVβ4, 14 were significantly expanded in CIS group, CD4⁺TCRVβ11 and CD8⁺TCRVβ9, 11 were significantly reduced in CIS group (P<0.05 or P<0.01). The amplification rate of CD4⁺TCRVβ2 (P=0.002) and CD8⁺TCRVβ14 (P=0.010) in CIS group were higher than those in normal control group, but there was no significant difference in the other subfamilies. There was no statistical difference in the expansion rate of the TCRVβ between CIS group and normal control group. The amplification number (P=0.001) and amplification fraction (P=0.006) of the TCRVβ in CIS group were significantly higher than the normal control group. Receiver operating characteristic curve (ROC) analysis indicated that the area under the curve (AUC) of CD4⁺TCRVβ4 in the diagnosis of CIS was 0.719 (95%CI:0.592-0.851, P=0.003). The sensitivity was 83.33%, the specificity was 56.67%. The AUC of CD4⁺ TCRVβ14 in the diagnosis of CIS was 0.713 (95% CI:0.581-0.845, P=0.005). The sensitivity was 70%, the specificity was 56.23%. The AUC of CD8⁺TCRVβ4 in the diagnosis of CIS was 0.727 (95%CI:0.600-0.854, P=0.002). The sensitivity was 93.33%, the specificity was 50%. The three fragments have medium diagnostic value for CIS. Conclusions Although the expression levels of CD4⁺ TCRVβ4, CD4⁺ TCRVβ14 and CD8⁺ TCRVβ4 in peripheral blood are increased in CIS group, their diagnostic value is limited.

Key words: Demyelinating diseases, Receptors, antigen, T-cell, alpha-beta, Polymorphism, genetic, Flow cytometry

摘要：

目的分析临床孤立综合征患者外周血T细胞受体β链可变区（TCRVβ）多态性，初步预测特异性TCRVβ片段，研究其对临床孤立综合征的诊断价值。方法选择2012年9月至2014年3月诊断并接受治疗的临床孤立综合征患者30例（CIS组），以同期行健康体检的30例受试者为正常对照组。流式细胞术检测常规免疫学指标和TCRVβ亚家族表达变化，CELL Quest Pro 5.1等相关软件分析24个TCRVβ亚家族成员表达水平，并计算扩增者比例、扩增个数和扩增分数。结果 TCRVβ 24个亚家族中，CIS组CD4⁺TCRVβ2、4、5.2、5.3、7.1、8、14、17、20、21.3片段，以及CD8⁺TCRVβ4、14片段表达水平高于正常对照组，而CD4⁺TCRVβ11和CD8⁺TCRVβ9、11片段表达水平低于正常对照组（P<0.05或P<0.01）。CIS组CD4⁺TCRVβ2（P=0.002）和CD8⁺TCRVβ14（P=0.010）扩增者比例均高于正常对照组，其余亚家族扩增者比例差异则无统计学意义（均P>0.05）。CIS组TCRVβ扩增者比例与正常对照组差异无统计学意义（P>0.05），但扩增个数（P=0.001）、扩增分数（P=0.006）均高于正常对照组。受试者工作特征（ROC）曲线显示，CD4⁺TCRVβ 4诊断临床孤立综合征的曲线下面积（AUC）为0.719（95% CI：0.592~0.851，P=0.003），灵敏度83.33%、特异度56.67%；CD4⁺TCRVβ14诊断的AUC为0.713（95% CI：0.581~0.845，P=0.005），灵敏度70%、特异度56.23%；CD8⁺TCRVβ4诊断的AUC为0.727（95% CI：0.600~0.854，P=0.002），灵敏度93.33%、特异度50%；以上3个片段对临床孤立综合征均具有中等诊断价值。。结论虽然临床孤立综合征患者外周血CD4⁺TCRVβ4、CD4⁺TCRVβ14和CD8⁺TCRVβ4片段表达水平升高，但其诊断价值有限。

关键词: 脱髓鞘疾病, 受体, 抗原, T细胞, &alpha, -&beta, 多态现象, 遗传, 流式细胞术

WU Yan, ZHANG Ji-hong, DONG Hui-qing, LI Da-wei, LIU Zheng, WAN Sui-gui. Polymorphism of peripheral blood T cell receptor β chain variable region in patients with clinically isolated syndrome[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2020, 20(9): 779-787.

吴岩, 张纪红, 董会卿, 李大伟, 刘峥, 万岁桂. 临床孤立综合征患者外周血T细胞受体β链可变区多态性研究[J]. 中国现代神经疾病杂志, 2020, 20(9): 779-787.

/ / Recommend / Download Citations

URL: https://journal11.magtechjournal.com/cjcnn/EN/10.3969/j.issn.1672-6731.2020.09.005

https://journal11.magtechjournal.com/cjcnn/EN/Y2020/V20/I9/779

References

[1] Schwenkenbecher P, Sarikidi A, Bönig L, Wurster U, Bronzlik P, Sühs KW, Pul R, Stangel M, Skripuletz T. Clinically isolated syndrome according to McDonald 2010:intrathecal IgG synthesis still predictive for conversion to multiple sclerosis[J]. Int J Mol Sci, 2017, 18:2061.
[2] Miller D, Barkhof F, Montalban X, Thompson A, Filippi M. Clinically isolated syndromes suggestive of multiple sclerosis, part Ⅰ:natural history, pathogenesis, diagnosis, and prognosis[J]. Lancet Neurol, 2005, 4:281-288.
[3] Allegretta M, Nicklas JA, Sriram S, Albertini RJ. T cells responsive to myelin basic protein in patients with multiple sclerosis[J]. Science, 1990, 247:718-721.
[4] Watson CT, Para AE, Lincoln MR, Ramagopalan SV, Orton SM, Morrison KM, Handunnetthi L, Handel AE, Chao MJ, Morahan J, Sadovnick AD, Breden F, Ebers GC. Revisiting the T-cell receptor alpha/delta locus and possible associations with multiple sclerosis[J]. Genes Immun, 2011, 12:59-66.
[5] Efendi H. Clinically isolated syndromes:clinical characteristics, differential diagnosis, and management[J]. Noro Psikiyatr Ars, 2015, 52:S1-11.
[6] Borràs E, Cantó E, Choi M, Maria V, Álvarez-Cermeño JC, Chiva C, Montalban X, Vitek O, Comabella M, Sabidó E. Protein-based classifier to predict conversion from clinically isolated syndrome to multiple sclerosis[J]. Mol Cell Proteomics, 2016, 15:318-328.
[7] Peixoto S, Abreu P. Magnetic resonance imaging conversion predictors of clinically isolated syndrome to multiple sclerosis[J]. Acta Med Port, 2016, 29:742-748.
[8] Brownlee WJ, Miller DH. Clinically isolated syndromes and the relationship to multiple sclerosis[J]. J Clin Neurosci, 2014, 21:2065-2071.
[9] Hou YL, Jia YJ, Hou JT. Natural course of clinically isolated syndrome:alongitudinal analysis using a Markov mode[J]. Sci Rep, 2018, 8:10857.
[10] Muraro PA, Jacobsen M, Necker A, Nagle JW, Gaber R, Sommer N, Oertel WH, Martin R, Hemmer B. Rapid identification of local T cell expansion in inflammatory organ diseases by flow cytometric T cell receptor Vbeta analysis[J]. J Immunol Methods, 2000, 246:131-143.
[11] Lossius A, Johansen JN, Vartdal F, Holmøy T. High-throughput sequencing of immune repertoires in multiple sclerosis[J]. Ann Clin Transl Neurol, 2016, 3:295-306.
[12] Wang CY, Fang YX, Chen GH, Jia HJ, Zeng S, He XB, Feng Y, Li SJ, Jin QW, Cheng WY, Jing ZZ. Analysis of the CDR3 length repertoire and the diversity of T cell receptor α and β chains in swine CD4+ and CD8+ T lymphocytes[J]. Mol Med Rep, 2017, 16:75-86.
[13] Warabi Y, Yagi K, Hayashi H, Matsumoto Y. Characterization of the T cell receptor repertoire in the Japanese neuromyelitisoptica:T cell activity is up-regulated compared to multiple sclerosis[J]. J Neurol Sci, 2006, 249:145-152.
[14] Mandel M, Achiron A, Tuller T, Barliya T, Rechavi G, Amariglio N, Loewenthal R, Lavie G. Clone clusters in autoreactive CD4 T-cell lines from probable multiple sclerosis patients form disease-characteristic signatures[J]. Immunology, 2009, 128:287-300.
[15] Slansky JE, Nakayama M. Peptide mimotopes alter T cell function in cancer and autoimmunity[J]. Semin Immunol, 2020, 47:101395.
[16] Venken K, Hellings N, Hensen K, Rummens JL, Stinissen P. Memory CD4+ CD127high T cells from patients with multiple sclerosis produce IL-17 in response to myelin antigens[J]. J Neuroimmunol, 2010, 226:185-191.
[17] Willing A, J äger J, Reinhardt S, Kursawe N, Friese MA. Production of IL-17 by MAIT cells is increased in multiple sclerosis and is associated with IL-7 receptor expression[J]. J Immunol, 2018, 200:974-982.
[18] van Nierop GP, van Luijn MM, Michels SS, Melief MJ, Janssen M, Langerak AW, Ouwendijk WJ, Hintzen RQ, Verjans GM. Phenotypic and functional characterization of T cells in white matter lesions of multiple sclerosis patients[J]. Acta Neuropathol, 2017, 134:383-401.
[19] Démoulins T, Mouthon F, Clayette P, Bequet D, Gachelin G, Dormont D. The same TCR (N) D beta (N) J beta junctional region is associated with several different Vbeta13 subtypes in a multiple sclerosis patient at the onset of the disease[J]. Neurobiol Dis, 2003, 14:470-482.
[20] Planas R, Metz I, Martin R, Sospedra M. Detailed characterization of T cell receptor repertoires in multiple sclerosis brain lesions[J]. Front Immunol, 2018, 9:509.

Please choose a citation manager

Content to export

Polymorphism of peripheral blood T cell receptor β chain variable region in patients with clinically isolated syndrome

临床孤立综合征患者外周血T细胞受体β链可变区多态性研究

RichHTML

PDF

Knowledge

Cited

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	SHA Jing, YANG Li-juan, Mayinuer Maimaiti, LI Hong-yan. The differential expression of CD4^- CD8^- double negative T lymphocytes in neuromyelitis optica spectrum disorders and multiple sclerosis [J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2020, 20(9): 788-793.
[2]	HAO Yu-bing, ZHANG An-ling, WANG Hu, WANG Guang-xiu, GAO Zhao, JIA Zhi-fan. Effect of protein kinase N1 on the biological behavior of human glioma [J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2020, 20(12): 1076-1084.
[3]	YU Ze-mou, LI Yong-chao, HAO Hong-jun, HUANG Yi-ning, PENG Qing. Myriocin reduces atherosclerosis in ApoE^-/- mice by inhibiting lipid-induced integrated stress response [J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2020, 20(10): 853-861.
[4]	ZHONG Xiao-nan, HU Xue-qiang. Research progress of idiopathic inflammatory demyelinating diseases [J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2018, 18(2): 99-109.
[5]	WEI Zi-long, DI Chong, LOU Mei-qing, ZHAO Yao-dong. Study on schizandrin A reversing drug resistance of glioma stem/progenitor cells by ATP binding cassette subfamily B member 1 [J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2017, 17(6): 439-445.
[6]	YANG Yi-han, CAI Li, MA Hai-wen, WANG Ying, BAI Yu, MING Hao-lang, YU Sheng-ping, REN Bing-cheng, LIN Yu, ZHANG Kai, HAI Long, WANG Wei, CHENG Cheng, LI Tao, YANG Xue-jun. MRI combined with ¹⁸F -FDG PET and ¹¹C -MET PET in differentiating tumefactive demyelinating lesion and glioma [J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2017, 17(10): 754-761.
[7]	GU Fu-rong, YAN Xiao-ling, QIN Jie, XU Xiao-lin. Clinical analysis of five cases of demyelinating pseudotumor [J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2017, 17(03): 214-222.
[8]	AN Zhong-ping, YANG Xun, ZHAO Wen-juan, HONG Yan, ZHOU Guan-en. Distribution of Th1, Th2 and Th17 in peripheral blood of patients with carotid atherosclerotic ischemic stroke [J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2016, 16(9): 591-597.
[9]	YU Qiao-yan, ZHAO Mei-ying. Tumor-like inflammatory demyelinating diseases of the central nervous system with relapse onset: one case report [J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2016, 16(10): 696-698.
[10]	HE Gui-nü, HAN Xiong, WANG En-feng, WANG Li-mei, YUAN Li-pin, LI Yan-wei, YAN Xi. Differential diagnosis of cervical spinal cord demyelinating diseases and cervical intramedullary gliomas [J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2014, 14(9): 789-794.
[11]	YAN Feng, ZHANG Yue-lin, YUE Wei, MAO Guo-chao, WANG Gang, ZUO Zhen-xing, GAO Ke. Experimental study on cultivation and purification of bone marrow-derived mesenchymal stem cells and its co-culture with chitosan porous scaffolds in vitro [J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2014, 14(11): 1000-1006.
[12]	LI Shou-hua, DENG Ju-feng, ZHANG Xiang-hai, LONG Chun-qin. Multiple sclerosis with brain demyelinating pseudotumor as first manifestation: a case report and review of literatures [J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2014, 14(1): 60-63.
[13]	FAN Cun-gang, WANG Dong-liang, ZHANG Qing-jun, ZHOU Jing-ru. The experimental investigation of glioma-trophic capacity of human umbilical cord-derived mesenchymal stem cells after intraventricular administration [J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2013, 13(7): 620-627.
[14]	ZHAO Zhen, BAO Zheng-jun, LUO Xiao-peng, PENG Zi-juan, CAO Xiao-ling, TANG Lan-ying. Evaluation of therapeutic efficacy on combined use of clopidogrel and ozagrel sodium in the treatment of acute ischemic stroke [J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2013, 13(10): 890-896.
[15]	FU Yu, TENG Yin-yan, XU Chao-wei, ZHANG Xu. The effect of bone marrow stem cells on the treatment of experimental autoimmune myasthenia gravis rat [J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2012, 12(2): 161-165.

模态框（Modal）标题

Please choose a citation manager

Content to export

Polymorphism of peripheral blood T cell receptor β chain variable region in patients with clinically isolated syndrome

临床孤立综合征患者外周血T细胞受体β链可变区多态性研究

RichHTML

PDF

Knowledge

Cited

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments