发热伴血小板减少综合征患者外周血淋巴细胞亚群变化特点
발열반혈소판감소종합정환자외주혈림파세포아군변화특점
Dynamic changes of peripheral blood lymphocyte subsets in fever with thrombocytopenia syndrome patients
  • 万方数据
    中华检验医学杂志 중화검험의학잡지
    CHINESE JOURNAL OF LABORATORY MEDICINE
    2012年 9期 826-831 ,共6页

    韩亚萍%周东辉%翁亚丽%董莉%陈念%张冬月%刘源%蒋龙凤%李爽%黄祖瑚%李军

    한아평%주동휘%옹아려%동리%진념%장동월%류원%장룡봉%리상%황조호%리군

    发热%血小板减少%布尼亚病毒科感染%淋巴细胞亚群%流式细胞术 髮熱%血小闆減少%佈尼亞病毒科感染%淋巴細胞亞群%流式細胞術
    발열%혈소판감소%포니아병독과감염%림파세포아군%류식세포술
    Fever%Thrombocytopenia%Bunyaviridae infections%Lymphocyte subsets%Flow cytometry
    目的 观察发热伴血小板减少综合征(SFTS)患者不同病程阶段外周血淋巴细胞亚群的动态变化特点,探讨其对疾病的发生、发展及预后的影响.方法 采用病例对照研究,收集江苏省人民医院2011年5-7月SFTS患者12例,诊断标准参照中华人民共和国卫生部发布的发热伴血小板减少综合征防治指南(2010版),按照临床预后分为痊愈组(9例)和死亡组(3例).32名健康对照者均为南京市中心血站健康献血者.采用流式细胞术动态定量检测健康对照者及SFTS患者在不同病程阶段外周血中CD3+即T细胞总数、CD4+即辅助性T细胞(Th细胞)、CD8+即细胞毒性T细胞(Te细胞)以及CD3 - CD16+ CD56+即自然杀伤细胞(NK细胞)表达水平,同时分析其与肝功能、血清酶学、WBC和PLT的关系.SFTS患者组与健康对照组间各淋巴细胞亚群计数的比较采用两独立样本t检验,5例以下小样本比较采用Mann-Whitney U检验.结果 SFTS痊愈组患者在病毒感染早期,Th/Tc比值倒置,外周血中Th细胞在病程第5天(d5)、d7、d9数量分别为(740.9±6.4)、(836.2±272.3)、(1083.6 ±319.7)个/μl,明显低于健康对照组的(1351.4±295.1)个/μl,差异有统计学意义(t值分别为-2.883、-4.235、-2.145,P均＜0.05)；外周血中Tc细胞在病程d7、d9、d11、d13、d15数量分别为( 1006.3±356.5)、(1166.4±242.4)、(1102.4±245.9)、(991.3 ±205.1)、(886.5±154.5)个/μl,明显高于健康对照组的(690.1±194.8)个/μl,差异有统计学意义(t值分别为3.312、5.661、4.574、3.874、2.382,P均＜0.05).至病程d9开始NK细胞明显下降；伴随细胞亚群的异常变化,患者外周血WBC和PLT计数显著下降,血清ALT、AST和LDH、CK等均明显高于正常范围,并随着CD4+细胞计数增加和淋巴细胞亚群恢复正常,大部分患者的WBC、PLT、ALT、AST、LDH、CK等指标也逐步恢复正常.SFTS死亡组患者则表现为T淋巴细胞总数和Th细胞显著减少,病程d7、d8、d9 T淋巴细胞总数分别为(735.9±359.9)、(724.9±125.9)、(845.3±389.3)个/μl;Th细胞计数分别为(533.2±246.9)、(532.1±105.7)、(551.7±86.9)个/μl,明显低于健康对照组的(1727.9±230.2)个/μl和(1351.4±295.1)个/μl,差异有统计学意义(Z值分别为- 2.828、-2.342、- 2.342和- 2.828、-2.342、- 2.342,P均＜0.05).NK细胞计数在病程d7、d8、d9分别为(1141.8±415.5)、(1047.2 ±68.4)、(1276.3 ±545.3)个/μl,显著高于健康对照组的(470.7±242.2)个/μl,差异有统计学意义(Z值分别为-2.180、-2.335、-2.258,P均＜0.05).结论 SFTS患者有明显的细胞免疫损伤,其淋巴细胞亚群的改变与临床分型及预后相关；外周血T淋巴细胞总数和CD4+细胞显著减少,同时伴有NK细胞显著增加,可能是SFTS患者预后不良的重要指标.
    목적 관찰발열반혈소판감소종합정(SFTS)환자불동병정계단외주혈림파세포아군적동태변화특점,탐토기대질병적발생、발전급예후적영향.방법 채용병례대조연구,수집강소성인민의원2011년5-7월SFTS환자12례,진단표준삼조중화인민공화국위생부발포적발열반혈소판감소종합정방치지남(2010판),안조림상예후분위전유조(9례)화사망조(3례).32명건강대조자균위남경시중심혈참건강헌혈자.채용류식세포술동태정량검측건강대조자급SFTS환자재불동병정계단외주혈중CD3+즉T세포총수、CD4+즉보조성T세포(Th세포)、CD8+즉세포독성T세포(Te세포)이급CD3 - CD16+ CD56+즉자연살상세포(NK세포)표체수평,동시분석기여간공능、혈청매학、WBC화PLT적관계.SFTS환자조여건강대조조간각림파세포아군계수적비교채용량독립양본t검험,5례이하소양본비교채용Mann-Whitney U검험.결과 SFTS전유조환자재병독감염조기,Th/Tc비치도치,외주혈중Th세포재병정제5천(d5)、d7、d9수량분별위(740.9±6.4)、(836.2±272.3)、(1083.6 ±319.7)개/μl,명현저우건강대조조적(1351.4±295.1)개/μl,차이유통계학의의(t치분별위-2.883、-4.235、-2.145,P균＜0.05)；외주혈중Tc세포재병정d7、d9、d11、d13、d15수량분별위( 1006.3±356.5)、(1166.4±242.4)、(1102.4±245.9)、(991.3 ±205.1)、(886.5±154.5)개/μl,명현고우건강대조조적(690.1±194.8)개/μl,차이유통계학의의(t치분별위3.312、5.661、4.574、3.874、2.382,P균＜0.05).지병정d9개시NK세포명현하강；반수세포아군적이상변화,환자외주혈WBC화PLT계수현저하강,혈청ALT、AST화LDH、CK등균명현고우정상범위,병수착CD4+세포계수증가화림파세포아군회복정상,대부분환자적WBC、PLT、ALT、AST、LDH、CK등지표야축보회복정상.SFTS사망조환자칙표현위T림파세포총수화Th세포현저감소,병정d7、d8、d9 T림파세포총수분별위(735.9±359.9)、(724.9±125.9)、(845.3±389.3)개/μl;Th세포계수분별위(533.2±246.9)、(532.1±105.7)、(551.7±86.9)개/μl,명현저우건강대조조적(1727.9±230.2)개/μl화(1351.4±295.1)개/μl,차이유통계학의의(Z치분별위- 2.828、-2.342、- 2.342화- 2.828、-2.342、- 2.342,P균＜0.05).NK세포계수재병정d7、d8、d9분별위(1141.8±415.5)、(1047.2 ±68.4)、(1276.3 ±545.3)개/μl,현저고우건강대조조적(470.7±242.2)개/μl,차이유통계학의의(Z치분별위-2.180、-2.335、-2.258,P균＜0.05).결론 SFTS환자유명현적세포면역손상,기림파세포아군적개변여림상분형급예후상관；외주혈T림파세포총수화CD4+세포현저감소,동시반유NK세포현저증가,가능시SFTS환자예후불량적중요지표.
    Objective The aim of this study is to dynamically investigate peripheral blood lymphocyte subsets in fever with thrombocytopenia syndrome (SFTS) patients at different stages,to evaluate the influence of these changes in the infection process.Methods Case-control study was used in the research.Twelve confirmed thrombocytopenia syndrome virus ( SFTSV ) infected patients were enrolled.According to SFTS prevention guide issued by Chinese Ministry of Health,these patients were divided into two groups,recovery group and death group.For each group,dynamic profiles of the CD3 + T cells,CD4 + helper T cells,CD8 + cytotoxic T cell and CD3 - CD16 + CD56 + natural killer cells were tested by flow cytometry.Meanwhile, the relationships between these dynamic changes and liver function,leukocytes,and platelets were analyzed respectively.Two independent-samples t test was used to compare the difference of the peripheral blood lymphocyte subsets count between the SFTS patients and healthy control.Small sample was analyzed by Mann-Whitney U test.Results In the early stage of infection,Th cells in peripheral blood of recovery group were significantly reduced and Th/Tc ratio was reversed.On day 5,7,9 of post infection,Th cell counts in peripheral blood were (740.9 ± 6.4),(836.2 ± 272.3 ) and ( 1083.6 ± 319.7 ) cells/μl respectively,which were significantly lower than health control ( 1351.4 ± 295.1 ) cells/μl ( t value was -2.883,-4.235,-2.145 respectively,all P ＜0.05).Tc cell counts were significantly more than healthy controls (690.1 ± 194.8) cells/μl through the course,which were ( 1006.3 ±356.5),(1166.4±242.4),(1102.4±245.9),(991.3±205.1) and (886.5±154.5) cells/μl on day 7,9,11,13,15 of the course (t value was 3.312,5.661,4.574,3.874,2.382,all P＜0.05).NK cells were decreased significantly from the ninth day of the course.Associated with abnormal changes of cell subsets,WBC and PLT decreased significantly,and serum ALT,AST,LDH and CK etc.were higher than normal level.With the disease recovery,the abnormality above was gradually improved.In contrast,death cases showed significant decrease in T and Th cells compared with health control (P ＜ 0.05).On day 7,8,9 of the course,the counts of total T cell were (735.9 ± 359.9),(724.9 ± 125.9),(845.3 ± 389.3) cells/μl and the counts of Th cell were ( 533.2 ± 246.9 ),( 532.1 ± 105.7 ),( 551.7 ± 86.9 ) cells/μl,significantly lower than healthy control ( 1727.9 ± 230.2 ) cells/μl and ( 1351.4 ± 295.1 ) cells/μl,with statistically differences (z value was - 2.828, - 2.342,- 2.342 and - 2.828, - 2.342, - 2.342,all P ＜ 0.05 ).On day 7,8,9 of the course,the numbers of NK cell in death group were ( 1141.8 ± 415.5),( 1047.2 ±68.4),( 1276.3 ±545.3) cells/μl,which were significantly more than health group (470.7 ± 242.2) cells/μl,with statistically differences (z value was - 2.180,- 2.335,- 2.258,all P ＜0.05).Conclusions SFTSV infection can induce cell immunity damage.The changes of lymphocyte subsets are associated with clinical classification and prognosis.Significant reduction of T cell and CD4 + cell in peripheral blood are accompanied with significant increase of NK cell,which may be a pivotal indicator of poor prognosis and play an important role in making appropriate strategy in clinical treatment.( Chin J Lab Med,2012,35:826-831 )
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