人类免疫缺陷病毒阴性隐球菌性脑膜炎患者外周血淋巴细胞亚群分析

中国真菌学杂志　 2017, Vol. 12 　Issue (5): 262-267.

人类免疫缺陷病毒阴性隐球菌性脑膜炎患者外周血淋巴细胞亚群分析

谢静^1,2, 葛瑛¹, 邱志峰¹, 张凯宇¹, 刘正印^1,2, 李太生^1,2

1. 中国医学科学院北京协和医学院北京协和医院感染内科, 北京 100730;
2. 中国医学科学院临床免疫中心, 北京 100730

收稿日期:2017-03-24 出版日期:2017-10-28 发布日期:2017-10-28
通讯作者: 葛瑛,E-mail:geyingpumch@126.com E-mail:geyingpumch@126.com
作者简介:谢静,女(汉族),博士,助理研究员.E-mail:xiejing@pumch.cn
基金资助:
国家科技支撑计划课题（2014BAI07B06），北京协和医院中青年科研基金（pumch-2016-2.3）

Immunophenotype of peripheral lymphocytes in HIV-negative patients with cryptococcal meningitis

XIE Jing^1,2, GE Ying¹, QIU Zhi-feng¹, ZHANG Kai-yu¹, LIU Zheng-yin^1,2, LI Tai-sheng^1,2

1. Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China;
2. Clinical Immunology Center, Chinese Academy of Medical Sciences, Beijing 100730, China

Received:2017-03-24 Online:2017-10-28 Published:2017-10-28

摘要/Abstract

摘要：

目的分析人类免疫缺陷病毒（Human immunodeficiency virus，HIV）阴性隐球菌性脑膜炎（Cryptococcal meningitis，CM）患者外周血淋巴细胞亚群改变特点，深化对隐球菌病发病机制的认识。方法筛选HIV阴性CM患者31例和健康献血员21例进行淋巴细胞亚群分析，CM患者根据是否存在免疫抑制基础疾病分为两个亚组，比较3组研究对象淋巴细胞亚群中B、NK、CD₄⁺T、CD₈⁺T细胞亚群，CD₄⁺T及CD₈⁺T细胞的第二信号受体CD₂₈表达比例及CD₈⁺T细胞激活标记物HLA-DR、CD₃₈的表达水平。结果有基础病CM组B、NK、CD₄⁺T和CD₈⁺T 4种亚群中位数依次为56×10⁶/L、86×10⁶/L、218×10⁶/L、164×10⁶/L，显著低于健康对照组的223×10⁶/L、280×10⁶/L、695×10⁶/L、521×10⁶/L（P值均<0.001），同时存在CD₈⁺T细胞激活亚群比例较健康对照显著升高。无基础病CM患者上述4种细胞亚群中位数依次为128×10⁶/L、128×10⁶/L、567×10⁶/L、527×10⁶/L，除CD₈⁺T细胞计数水平与健康对照相似以外，B（P=0.02）、NK（P=0.002）和CD₄⁺T细胞（P=0.03）计数均低于健康对照，其CD₈⁺T细胞激活亚群比例与健康对照组相似。CD₄⁺T和CD₈⁺T细胞的CD₂₈表达水平在3组间未见显著差异。结论 HIV阴性CM患者，无论是否存在免疫抑制基础疾病，外周血B、NK及CD₄⁺T 3种细胞计数可出现同时减少。

关键词: 脑膜炎,隐球菌性, 淋巴细胞亚群, CD₄⁺T细胞

Abstract:

Objective To find if immunophenotypic features of peripheral lymphocytes was associated with risk of cryptococcal meningitis (CM) in HIV-negative individuals.Methods A total of 31 CM patients treated at a tertiary hospital in Beijing,China were included.They were divided into immunocompromised comorbidity group (n=16) and apparently immunocompetent group (n=15).Twenty-one healthy donors were included as control group.Lymphocyte subsets including B,NK,CD₄⁺T,and CD₈⁺T cells,CD₂₈ expression on T cells,and activation markers (HLA-DR and CD₃₈) on CD₈⁺T cells were determined by flow cytometry and compared among the three groups.Results Compared with healthy donors,immunocompromised comorbidity group had dramatically decreased median B cell (223 vs.56/μL),NK cell (280 vs.86/μL),CD₄⁺T cell (695 vs.218/μL),and CD₈⁺T cell (521 vs.164/μL) counts (P values for all four subsets<0.001).Proportions of activated CD₈⁺T cells were significantly increased in immunocompromised patients than that in healthy control.Except for CD₈⁺T cell counts (527/μL),the median B cell (128/μL,P=0.02),NK cell (128/μL,P=0.002) and CD₄⁺T cell (567/μL,P=0.03) were moderately reduced in the apparently immunocompetent group than those in the healthy donors.The levels of HLA-DR and CD₃₈ on CD₈⁺T cells in the apparently immunocompetent group were similar with the healthy donors.CD₂₈ expression on CD₄⁺T and CD₈⁺T cells did not differ among the three groups.Conclusions The immunophenotype of CM patients with im-munocompromised comorbidity was characterized by generalized decreased B,NK,CD₄⁺T,and CD₈⁺T cells.Mild-to-moderate reduce in B cell,NK cell and CD₄⁺T cell counts were observed in apparently immunocompetent patients.

Key words: cryptococcal meningitis, lymphocyte subsets, CD₄⁺T cell

中图分类号:

R519.4

谢静, 葛瑛, 邱志峰, 张凯宇, 刘正印, 李太生. 人类免疫缺陷病毒阴性隐球菌性脑膜炎患者外周血淋巴细胞亚群分析[J]. 中国真菌学杂志, 2017, 12(5): 262-267.

XIE Jing, GE Ying, QIU Zhi-feng, ZHANG Kai-yu, LIU Zheng-yin, LI Tai-sheng. Immunophenotype of peripheral lymphocytes in HIV-negative patients with cryptococcal meningitis[J]. Chinese Journal of Mycology, 2017, 12(5): 262-267.

参考文献

[1] Bowen LN,Smith B,Reich D,et al.HIV-associated opportunistic CNS infections:pathophysiology,diagnosis and treatment[J].Nat Rev Neurol,2016,12(11):662-674.
[2] Bamba S,Lortholary O,Sawadogo A,et al.Decreasing incidence of cryptococcal meningitis in West Africa in the era of highly active antiretroviral therapy[J].AIDS,2012,26(8):1039-1041.
[3] Pappas PG,Perfect JR,Cloud GA,et al.Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy[J].Clin Infect Dis,2001,33(5):690-699.
[4] Chau TT,Mai NH,Phu NH,et al.A prospective descriptive study of cryptococcal meningitis in HIV uninfected patients in Vietnam-high prevalence of Cryptococcus neoformans var grubii in the absence of underlying disease[J].BMC Infect Dis,2010,10:199.
[5] Tan ZR,Long XY,Li GL,et al.Spectrum of neuroimaging findings in cryptococcal meningitis in immunocompetent patients in China-A series of 18 cases[J].J Neurol Sci,2016,368:132-137.
[6] 刘加,方文捷,洪南,等.免疫正常人群隐球菌性脑膜炎临床分析[J].中国真菌学杂志,2016,11(2):99-102.
[7] 林苏,张彦亮,邵凌云,等.隐球菌性脑膜炎并发颅神经损伤的危险因素及预后因素分析[J].中华传染病杂志,2013,31(3):155-159.
[8] 刘正印,王爱霞,李太生,等.隐球菌性脑膜炎26例临床分析[J].中华内科杂志,2002,41(8):541-543.
[9] Xu L,Huang Q,Lin JR,et al.Clinical immunophenotype at disease onset in previously healthy patients with cryptococcal meningitis[J].Medicine (Baltimore),2016,95(6):e2744.
[10] Panackal AA,Wuest SC,Lin YC,et al.Paradoxical immune responses in Non-HIV cryptococcal meningitis[J].PLoS Pathog 2015,11(5):e1004884.
[11] Chen J,Varma A,Diaz MR,et al.Cryptococcus neoformans strains and infection in apparently immunocompetent patients,China[J].Emerg Infect Dis,2008,14(5):755-762.
[12] 朱利平,翁心华.非艾滋病相关隐球菌脑膜炎的新认识[J].临床内科杂志,2011,28(8):521-523.
[13] Williamson PR,Jarvis JN,Panackal AA,et al.Cryptococcal meningitis:epidemiology,immunology,diagnosis and therapy[J].Nat Rev Neurol,2017,13(1):13-24.
[14] 中华医学会感染病学分会艾滋病学组.艾滋病诊疗指南第三版(2015版)[J].中华临床感染病杂志,2015,8(5):385-401.
[15] Corneau A,Cosma A,Even S,et al.Comprehensive mass cytometry analysis of cell cycle,activation,and coinhibitory receptors expression in CD₄ T cells from healthy and HIV-infected individuals[J].Cytometry B Clin Cytom,2017,92(1):21-32.
[16] Quarona V,Zaccarello G,Chillemi A,et al.CD₃₈ and CD157:a long journey from activation markers to multifunctional molecules[J].Cytometry B Clin Cytom,2013,84(4):207-217.
[17] Bijl M,Horst G,Limburg PC,et al.Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus (SLE):relation to lymphocyte activation and disease activity[J].Lupus,2001,10(12):866-872.
[18] Cao W,Qiu ZF,Li TS.Parallel decline of CD₈⁺CD₃₈⁺ lymphocytes and viremia in treated hepatitis B patients[J].World J Gastroenterol,2011,17(17):2191-2198.
[19] Fang W,Fa Z,Liao W.Epidemiology of Cryptococcus and cryptococcosis in China[J].Fungal Genet Biol,2015,78:7-15.