肺炎伴巨细胞病毒感染患儿外周血免疫功能分析
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摘要
目的探讨肺炎伴巨细胞病毒感染患儿的外周血免疫功能状态。方法选取2012年1月至2016年9月南京医科大学第一附属医院收治的2个月～2岁肺炎患儿共154例,按照巨细胞病毒(CMV)病原学检测结果分为CMV阳性组(90例)和CMV阴性组(64例),对两组患儿的临床资料和实验室指标进行回顾性分析。比较两组肺炎患儿的外周血细胞计数以及住院时间,根据血细胞参数分析系统性炎症反应相关指标包括中性粒细胞/淋巴细胞(NLR)、血小板/淋巴细胞(PLR)、淋巴细胞/单核细胞(LMR)和系统性免疫性炎症指数(SII)(中性粒细胞/淋巴细胞×血小板)的差异。结果与CMV阴性组患儿相比,CMV阳性组患儿外周血白细胞[(7.83±2.92)×10~9/L vs.(9.59±4.03)×10~9/L,Z=-4.291、P <0.001]、单核细胞[(0.63±0.35)×10~9/L vs.(0.78±0.47)×10~9/L,Z=-3.104、P=0.002]、中性粒细胞[(1.73±1.60)×10~9/L vs.(2.64±1.65)×10~9/L,Z=-5.017、P <0.001]和血小板[(331.50±140.50)×10~9/L vs.(364.00±163.80)×10~9/L,Z=-2.013、P=0.044]计数均显著降低,差异均有统计学意义。CMV阳性组患儿NLR[(0.35±0.35) vs.(0.51±0.50),Z=-3.388、P <0.001]和SII[(107.10±133.16) vs.(182.40±173.3),Z=-4.029、P <0.001]较CMV阴性组患儿亦显著降低,差异均有统计学意义。CMV阳性组患儿较CMV阴性组患儿住院时间延长[(9.12±2.88) vs.(8.28±1.79)d,Z=-2.063、P=0.039],住院时间超过2周的患儿比例亦升高(14.44%vs. 1.56%,χ~2=7.510、P=0.006),差异均有统计学意义。结论伴巨细胞病毒感染的肺炎患儿存在外周血细胞免疫功能紊乱。
Objective To evaluate the peripheral immune status of pneumonia infants with cytomegalovirus(CMV) infection. Methods Total of 154 infants aged 2 to 24 months with pneumonia were recruited from January 2012 to September 2016 in the First Affiliated Hospital of Nanjing Medical University.According to the results of cytomegalovirus pathogen detection, 154 cases were divided into two groups:CMV positive group(90 cases) and CMV negative group(64 cases). The clinical data and laboratory results were analyzed, retrospectively. The peripheral blood cell counts and the hospitalization stay of two groups of children with pneumonia were compared, respectively. According to the parameters of blood cells, the related indexes of systemic inflammatory reaction including neutrophil/lymphocyte(NLR), platelet/lymphocyte(PLR),differences of lymphocyte/monocyte(LMR) and systemic immune inflammatory index(SII)(neutrophil/lymphocyte × platelet) were analyzed, respectively. Results Compared with CMV negative group, the counts of peripheral leukocytes [(7.83 ± 2.92) × 10~9/L vs.(9.59 ± 4.03) × 10~9/L, Z =-4.291, P < 0.001], monocytes[(0.63 ± 0.35) × 10~9/L vs.(0.78 ± 0.47) × 10~9/L; Z =-3.104, P = 0.002], neutrophils [(1.73 ± 1.60) × 10~9/L vs.(2.64 ± 1.65) × 10~9/L; Z =-5.017, P < 0.001] and platelets counts [(331.50 ± 140.50) × 10~9/L vs.(364.00 ±163.80) × 10~9/L; Z =-2.013, P = 0.044] of cases in CMV positive group decreased significantly; NLR[(0.35 ± 0.35) vs.(0.51 ± 0.50); Z =-3.388, P < 0.001] and SII [(107.10 ± 133.16) vs.(182.40 ± 173.3); Z =-4.029, P < 0.001] also decreased significantly. The hospitalization stay of cases in CMV-positive group was significantly longer than that of the CMV-negative group [(9.12 ± 2.88) vs.(8.28 ± 1.79) d; χ~2 =-2.063, P =0.039], and the proportion of children with hospitalization stay longer than 2 weeks in CMV-positive group was higher than that of CMV-negative group, with significant difference(14.44% vs. 1.56%; χ~2 = 7.510, P =0.006). Conclusions Peripheral blood immune dysfunction exists in pneumonia infants with cytomegalovirus infection.
Objective To evaluate the peripheral immune status of pneumonia infants with cytomegalovirus(CMV) infection. Methods Total of 154 infants aged 2 to 24 months with pneumonia were recruited from January 2012 to September 2016 in the First Affiliated Hospital of Nanjing Medical University.According to the results of cytomegalovirus pathogen detection, 154 cases were divided into two groups:CMV positive group(90 cases) and CMV negative group(64 cases). The clinical data and laboratory results were analyzed, retrospectively. The peripheral blood cell counts and the hospitalization stay of two groups of children with pneumonia were compared, respectively. According to the parameters of blood cells, the related indexes of systemic inflammatory reaction including neutrophil/lymphocyte(NLR), platelet/lymphocyte(PLR),differences of lymphocyte/monocyte(LMR) and systemic immune inflammatory index(SII)(neutrophil/lymphocyte × platelet) were analyzed, respectively. Results Compared with CMV negative group, the counts of peripheral leukocytes [(7.83 ± 2.92) × 10~9/L vs.(9.59 ± 4.03) × 10~9/L, Z =-4.291, P < 0.001], monocytes[(0.63 ± 0.35) × 10~9/L vs.(0.78 ± 0.47) × 10~9/L; Z =-3.104, P = 0.002], neutrophils [(1.73 ± 1.60) × 10~9/L vs.(2.64 ± 1.65) × 10~9/L; Z =-5.017, P < 0.001] and platelets counts [(331.50 ± 140.50) × 10~9/L vs.(364.00 ±163.80) × 10~9/L; Z =-2.013, P = 0.044] of cases in CMV positive group decreased significantly; NLR[(0.35 ± 0.35) vs.(0.51 ± 0.50); Z =-3.388, P < 0.001] and SII [(107.10 ± 133.16) vs.(182.40 ± 173.3); Z =-4.029, P < 0.001] also decreased significantly. The hospitalization stay of cases in CMV-positive group was significantly longer than that of the CMV-negative group [(9.12 ± 2.88) vs.(8.28 ± 1.79) d; χ~2 =-2.063, P =0.039], and the proportion of children with hospitalization stay longer than 2 weeks in CMV-positive group was higher than that of CMV-negative group, with significant difference(14.44% vs. 1.56%; χ~2 = 7.510, P =0.006). Conclusions Peripheral blood immune dysfunction exists in pneumonia infants with cytomegalovirus infection.
引文
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[21]Zhao Z,Liu J,Wang J,et al.Platelet-to-lymphocyte ratio(PLR)and neutrophil-to-lymphocyte ratio(NLR)are associated w i t h c h r o n i c h e p a t i t i s B v i r u s(H B V)i n f e c t i o n[J].I n t Immunopharmacol,2017,51:1-8.
[22]Kim HA,Jung JY,Suh CH.Usefulness of neutrophil-to-lymphocyte ratio as a biomarker for diagnosing infections in patients with systemic lupus erythematosus[J].Clin Rheumatol,2017,36(11):2479-2485.
[23]Jenne CN,Kubes P.Platelets in inflammation and infection[J].Platelets,2015,26(4):286-292.
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[25]Izadnegahdar R,Cohen AL,Klugman KP,et al.Childhood pneumonia in developing countries[J].Lancet Respir Med,2013,1(7):574-584.
[2]Sanbonmatsu Gamez S,Ruiz MP,Navarro Mari JM.Infection by humancy to megalovirus][J].Enferm Infecc Microbiol Clin,2014,32(Suppl 1):15-22.
[3]Bohm V,Seckert CK,Simon CO,et al.Immuneevasion proteins enhance cytomegalovirus latency in the lungs[J].JVirol,2009,83(19):10293-10298.
[4]Restrepo-Gualteros SM,Jaramillo-Barberi LE,Gonzalez-Santos M,et al.Characterization of cytomegalovirus lung infection in non-HIVinfected children[J].Viruses,2014,6(5):2038-2051.
[5]Walker CL,Rudan I,Liu L,et al.Global burden of childhood pneumonia and diarrhoea[J].Lancet,2013,381(9875):1405-1416.
[6]Guan X,Silk BJ,Li W,et al.Pneumonia incidence and mortality in Mainland China:systematic review of Chinese and English literature,1985-2008[J].PLoS One,2010,5(7):e11721.
[7]Fowler KB,Boppana SB.Congenital cytomegalovirus infection[J].Semin Perinatol,2018,42(3):149-154.
[8]张鑫婷,于泽堃,韩宗来,等.新生儿巨细胞病毒肺炎诊断及治疗[J].中国妇幼保健,2018,33(15):3597-3600.
[9]Pawelec G.Immunosenenescence:role of cytomegalovirus[J].Exp Gerontol,2014,54:1-5.
[10]卢光全,李儒贵,谭华炳,等.85例巨细胞病毒感染婴幼儿的临床特征[J/CD].中华实验和临床感染病杂志(电子版),2017,11(3):282-286.
[11]Goncalves C,Cipriano A,Videira Santos F,et al.Cytomegalovirus acute infection with pulmonary involvement in an immunocompetent patient[J].IDCases,2018,14:e00445.
[12]宋恩杰.巨细胞病毒性肺炎儿童体内淋巴细胞亚群的变化特点[J].中国疗养医学,2018,27(1):65-67.
[13]Simmons P,Kaushansky K,Torok-Storb B.Mechanisms of cytomegalovirus-mediated myelosuppression:perturbation of stromal cell function versus direct infection of myeloid cells[J].Proc Natl Acad Sci USA,1990,87(4):1386-1390.
[14]Botto S,Streblow DN,DeFilippis V,et al.IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of survivin[J].Blood,2011,117(1):352-561.
[15]Murayama T,Mukaida N,Khabar KS,et al.Potential involvement of IL-8 in the pathogenesis of human cytomegalovirus infection[J].JLeukoc Biol,1998,64(1):62-67.
[16]Almeida-Porada GD,Ascensao JL.Cytomegalovirus as a cause of pancytopenia[J].Leuk Lymphoma,1996,21(3-4):217-223.
[17]Jackson SE,Sedikides G X,Mason G M,et al.Humancy tomegalovirus(HCMV)-specific CD4(+)T cells are polyfunctional and can respond to HCMV-infected dendritic cells in vitro[J].JVirol,2017,91(6):e02128-16.
[18]Vieira Braga FA,Hertoghs KM,van Lier RA,et al.Molecular characterization of HCMV-specific immune responses:Parallels between CD8(+)T cells,CD4(+)T cells,and NK cells[J].Eur JImmunol,2015,45(9):2433-2445.
[19]Stevenson EV,Collins-McMillen D,Kim JH,et al.HCMVreprogramming of infected monocyte survival and differentiation:a Goldilocks phenomenon[J].Viruses,2014,6(2):782-807.
[20]Yamin R,Lecker LSM,Weisblum Y,et al.HCMV vCXCL1binds several chemokine receptors and preferentially attracts neutrophils over NK cells by interacting with CXCR2[J].Cell Rep,2016,15(7):1542-1553.
[21]Zhao Z,Liu J,Wang J,et al.Platelet-to-lymphocyte ratio(PLR)and neutrophil-to-lymphocyte ratio(NLR)are associated w i t h c h r o n i c h e p a t i t i s B v i r u s(H B V)i n f e c t i o n[J].I n t Immunopharmacol,2017,51:1-8.
[22]Kim HA,Jung JY,Suh CH.Usefulness of neutrophil-to-lymphocyte ratio as a biomarker for diagnosing infections in patients with systemic lupus erythematosus[J].Clin Rheumatol,2017,36(11):2479-2485.
[23]Jenne CN,Kubes P.Platelets in inflammation and infection[J].Platelets,2015,26(4):286-292.
[24]Britt WJ,Prichard MN.New therapies for human cytomegalovirus infections[J].Antiviral Res,2018,159:153-174.
[25]Izadnegahdar R,Cohen AL,Klugman KP,et al.Childhood pneumonia in developing countries[J].Lancet Respir Med,2013,1(7):574-584.