病毒性肺炎患儿自然杀伤细胞亚群、T细胞亚群及血IL-2、IL-4、INF-γ变化的研究

目的 探讨病毒性肺炎患儿自然杀伤(NK)细胞亚群、T细胞亚群及血IL-2、IL-4、INF-γ的动态变化及临床意义.方法 采用流式细胞术测定32例病毒性肺炎患儿急性期(肺炎起病2?d内)、恢复期(肺炎起病5?d内)外周血NK细胞亚群、T细胞亚群,用ELISA法测定血IL-2、IL-4、INF-γ水平,用乳酸脱氢酶释放法测定NK细胞活性变化,并与30例健康对照组儿童进行比较.结果 (1) 病毒性肺炎患儿CD16+CD56+、CD16+NK细胞在急性期分别为(0.73±0.17)%、(0.39±0.2)%,恢复期分别为(1.47±0.22)%、(0.89±0.14)%;急性期与恢复期比较,恢复期CD16+CD56+、CD16+NK细胞明显升高(P<0.01),但均显著低于对照组(P<0.01).两组NK细胞亚群变化与其活性改变呈正相关.病毒性肺炎患儿CD56+NK细胞与健康儿童差异无显著性(P>0.05).(2) 与对照组相比,病毒性肺炎患儿的急性期、恢复期IL-2、IL-4均无明显改变,差异无显著性(P>0.05);急性期INF-γ无明显改变,差异无显著性(P>0.05),而恢复期INF-γ[(28.10±1.38)?μg/L]明显高于急性期[(22.78±1.19)?μg/L],差异有非常显著性(P<0.01).(3) 与对照组相比,病毒性肺炎患儿CD4+、CD4+/CD8+T细胞计数在急性期与恢复期均无明显改变,差异无显著性(P>0.05).病毒性肺炎急性期、恢复期CD8+T细胞均低于对照组,差异有显著性(P<0.05),但病毒性肺炎急性期、恢复期间差异无显著性(P>0.05).结论 病毒性肺炎患儿NK细胞活性降低,活性与亚群数目呈正相关;病毒性肺炎患儿抑制性T细胞功能低下.病毒性肺炎急性期NK细胞激活是多因素共同作用的结果 .     

人类偏肺病毒毛细支气管炎患儿细胞免疫分析

目的 探讨人类偏肺病毒(human metapneumovirus,hMPV)感染致毛细支气管炎患儿细胞免疫功能的变化.方法 用RT-PCR方法对255例毛细支气管炎住院患儿的呼吸道分泌物进行hMPV N基因检测,以明确hMPV感染.采用流式细胞仪检测患儿外周血T淋巴细胞亚群B淋巴细胞和NK细胞,以30例健康儿童作为对照组.结果 共检测到51份RT-PCR阳性扩增产物,阳性率为20.0%;hMPV感染组外周血 CD3+T细胞、CD4+T细胞、CD8+T细胞与对照组比较差异无统计学意义,CD19+、CD19+CD23+、CD4+CD25+T细胞均明显增高(P<0.01),而NK细胞下降(P<0.05).结论 hMPV是毛细支气管炎的重要病原之一,hMPV感染后机体细胞免疫功能明显紊乱.     

儿童噬血细胞性淋巴组织细胞增生症淋巴细胞亚群变化及临床意义

目的探讨外周血淋巴细胞亚群对儿童噬血细胞性淋巴组织细胞增生症(HLH)诊断、治疗和预后判断的意义。方法 30例HLH患儿,采用HLH-2004诊断治疗方案,20例患儿获得完全缓解,10例死亡。30例同龄健康儿童作为正常对照。采用流式细胞术检测外周血淋巴细胞亚群。结果 20例缓解患儿和10例死亡患儿急性期与正常对照组比较,CD3+T和CD8+T细胞比例均增高,CD4+T和CD3-CDl6+CD56+NK细胞比例均下降,CD4+/CD8+比值减低,差异均有统计学意义(H=7.857~45.448,P均0.05);CD19+B细胞比例与对照组比较,差异无统计学意义(H=6.202,P0.05)。20例HLH缓解患儿缓解期与急性期淋巴细胞亚群比较,CD3-CD16+CD56+NK细胞比例的差异有统计学意义(Z=3.760,P0.05),CD3+T、CD8+T、CD4+T和CD4+/CD8+比值、CD19+B计数差异无统计学意义(Z=0.135~1.082,P均0.05)。结论 HLH患儿淋巴细胞亚群有明显变化,存在细胞免疫失衡;动态检测其变化可能有助于判断HLH的治疗效果及预后。     

急性白血病患儿外周血T淋巴细胞亚群和NK细胞水平测定及临床意义

为探讨急性白血病患儿外周血T淋巴细胞亚群和NK细胞水平及意义 ,采用流式细胞技术测定 90例急性白血病患儿外周血T淋巴细胞亚群和NK细胞水平。结果 ,急性白血病患儿外周血T淋巴细胞亚群中CD3+ 、CD4+ 、CD4+ CD8+ 均明显低于对照组水平 (P <0 0 1) ,CD8+ 高于对照组水平 (P <0 0 1) ,NK细胞 (CD1 6+ 56+ )明显低于对照组水平 (P <0 0 1) ,经治疗缓解者T淋巴细胞亚群和NK细胞达正常水平。结果表明 ,T淋巴细胞亚群和NK细胞可作为急性白血病辅助诊断指标 ,为临床治疗提供实验依据     

儿童EB病毒感染的免疫功能状况

目的研究EB病毒(EBV)感染儿童免疫功能状况及其与临床和预后的关系。方法用流式细胞仪(FCM)分别对30例传染性单核细胞增多症(IM)患儿急性期、恢复期外周血淋巴细胞CD3 、CD4 、CD8 、CD19 、CD23 抗原进行检测,并与20例同龄健康对照组儿童比较。结果IM患儿急性期CD4 、CD8 、CD19 、CD23 淋巴细胞百分率分别为(14.88±3.14)%,(65.49±5.33)%,(5.70±2.89)%,(2.41±1.83)%,恢复期为(36.75±3.88)%,(41.64±5.11)%,(15.98±2.80)%,(5.02±2.76)%。急性期CD8 明显高于恢复期和对照组,而CD4 、CD19 、CD23 淋巴细胞明显低于恢复期和对照组。恢复期3例CD23 细胞比值较高。结论EBV感染儿童外周血淋巴细胞亚群明显异常,CD23 细胞的持续增高与CD4 T细胞的长期低下有可能成为评价IM预后的指标。     

以流式细胞术建立中国汉族健康儿童外周血淋巴细胞亚群相对计数的正常参考值

目的建立中国汉族健康儿童外周血淋巴细胞亚群的正常参考值范围。方法选取首都医科大学附属北京儿童医院入托、入学体检,或术前查体及术后复查(均为对免疫功能影响不大的疾病)的0～18岁汉族儿童为研究对象。按年龄分为婴儿组(28d至12个月),幼儿组(～3岁),学龄前组(～7岁),学龄组(～12岁)和青春期组(～18岁)。采集外周血以双色及四色荧光标记流式细胞术检测淋巴细胞亚群T细胞(CD3+CD19-)、CD4+T细胞(CD3+CD4+)、CD8+T细胞(CD3+CD8+)、B细胞(CD3-CD19+)和NK细胞(CD3-CD16+CD56+)相对计数及CD4+/CD8+比值。比较各年龄组不同性别淋巴细胞亚群分布的差异,建立正常参考值范围。结果由于青春期组所收集的标本数较少,将该研究对象组予以删除。最终纳入28d至12岁儿童592例。①婴儿组T细胞、CD8+T细胞百分比与CD4+/CD8+比值性别差异均有统计学意义,幼儿组CD4+T细胞、CD8+T细胞百分比与CD4+/CD8+比值性别差异均有统计学意义,学龄组CD4+T细胞百分比性别差异有统计学意义;②除了男童T细胞百分比各年龄组间差异无统计学意义外,男女儿童各年龄组间外周各血淋巴细胞亚群分布总体上差异均有统计学意义;进一步行男女儿童淋巴细胞亚群不同年龄组间两两比较,发现多个年龄组间差异有统计学意义;③男女儿童T细胞、CD8+T细胞和NK细胞百分比随年龄增长均呈逐渐升高趋势;CD4+T细胞、B细胞百分比及CD4+/CD8+比值随年龄增长均呈逐渐降低趋势;男女儿童T细胞、B细胞、NK细胞百分比和CD4+/CD8+比值升高或降低的程度略有不同;④中国汉族健康儿童淋巴细胞亚群分布特点与欧、美、非洲国家儿童相比存在相似的升高或降低的趋势,但数值上存在一定的差异。结论儿童淋巴细胞亚群分布存在年龄和性别的差异。本研究成功建立中国汉族28d至12岁健康儿童淋巴细胞亚群相对计数正常参考值范围。     

肠套叠患儿外周血Th1/Th2的漂移

目的 探索肠套叠患儿细胞免疫状况的变化.方法 采用流式细胞仪检测肠套叠患儿急性期及对照组外周血T辅助淋巴细胞Th1和Th2的百分率、CD3、CIN+、CD8+、NK细胞、B细胞百分率及C1N/CD8比值.对10例肠套叠恢复期患儿复查淋巴细胞亚群.结果 肠套叠患儿急性期外周血Th1细胞百分率(15.98±9.83)%明显低于对照组(20.83±6.79)%(P＜0.05);肠套叠组Th2细胞百分率(5.48±1.86)%较对照组(4.31±2.02)%明显增高(P＜0.05).Th1/Th2比值,肠套叠组为3.51±2.49,对照组为5.89±3.14,二组比较有非常显著性差异(P＜0.01).急性期NK细胞百分率明显降低(P＜0.05),但肠套叠组B细胞、CD3、CIN+、CD8+及CD4/CD8与对照组比较均无统计学差异(P＞0.05).10例肠套叠缓解期患儿淋巴细胞亚群结果表明,NK细胞百分率显著升高(P＜0.05),其他各项指标在急性期与缓解期无明显差异.结论 肠套叠患儿最重要的免疫异常是Th1/Th2细胞比例和功能失衡,主要表现为Th2细胞应答优势存在,Th1/Th2显著降低.肠套叠急性期肠道抗感染免疫力下降.     

急性特发性血小板减少性紫癜患儿T细胞亚群、NK细胞及IFN-γ、IL-4变化的探讨

目的通过检测急性特发性血小板减少性紫癜(ITP)患儿T细胞亚群、NK细胞、IFN-γ、IL-4,探讨急性ITP患儿的发病机制。方法采用流式细胞仪检测32例急性ITP患儿及20例对照儿童外周血T细胞亚群、NK细胞比例,采用双抗体夹心酶联免疫吸附试验定量方法检测两组儿童外周血IFN-γ、IL-4水平,并采用t检验和直线相关分析进行比较分析。结果急性ITP患儿CD3+、CD4+、CD4+/CD8+细胞水平均明显低于对照组(P值均<0.001),CD8+细胞水平明显高于对照组(P<0.001);NK细胞水平与对照组比较差异无显著性(P>0.05);血清IFN-γ水平明显高于对照组(P<0.01),IL-4水平明显低于对照组(P<0.01);CD4+、CD8+细胞百分比的改变与血小板计数无明显相关性(P>0.05),IFN-γ与IL-4水平呈明显负相关(P<0.001)。结论急性ITP患儿存在T淋巴细胞亚群失衡,同时存在细胞因子紊乱,可能是Th1优势疾病,NK细胞与儿童急性ITP发病机制的关系尚不明确。     

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目的探讨甲型H1N1流感患儿感染后细胞免疫功能的变化。方法回顾性分析2009年10月至2010年1月苏州大学附属儿童医院收治的86例甲型H1N1流感确诊病例(分成危重组和重症组)的临床资料;采用流式细胞仪检测患儿外周血T淋巴细胞、B淋巴细胞和NK细胞亚群比例。以23例外科住院患儿的淋巴细胞亚群作为对照组来观察甲型H1N1流感患儿的细胞免疫功能变化特征。结果 (1)CD3+、CD3+CD4+、CD3+CD8+亚群百分比:重症组和危重组较对照组明显降低,而该两组之间差异无统计学意义;(2)CD3-CD19+、CD19+CD23+亚群百分比统计结果示危重组>重症组>对照组,各组间比较有统计学意义(P<0.05);(3)CD3-CD16+CD56+亚群百分比在重症患儿和对照组之间差异无统计学意义,危重组较其他两组均有显著下降;(4)CD4+/CD8+比值在各组之间差异无统计学意义。结论甲型H1N1流感患儿感染后细胞免疫功能存在明显紊乱:T淋巴细胞受到全面抑制,B淋巴细胞激活参与病毒的清除,NK细胞比例的降低与危重患儿的病情相关。     

儿童严重脓毒症免疫功能的变化

目的 探讨儿童严重脓毒症体液免疫、淋巴细胞亚群和NK细胞水平变化,与病情严重程度及预后的关系.方法 2013年3月至2017年2月,上海交通大学附属儿童医院重症医学科收治严重脓毒症患儿共224例,其中82例于入PICU 24h内和治疗7d后至少2次进行体液免疫(IgG、IgM、IgA)、细胞免疫[淋巴细胞亚群CD3+、CD4+、CD8+、CD19+]和NK细胞(CD16+56+)测定,比较存活组(59例)与死亡组(23例)、不同器官功能状态患儿(累及出现器官功能障碍个数>3个共36例,2~3个共30例,1个共16例)的免疫功能变化.同期体检儿童15例作为正常对照组.结果 (1)严重脓毒症患儿入PICU时血NK细胞明显低于正常,治疗7 d后存活组NK细胞数量升高[(3.7±1.9)% 比(11.5±1.9)%,P<0.05];严重脓毒症组与正常对照组IgG、IgM、IgA比较差异无统计学意义(均P>0.05),而淋巴细胞亚群中CD3+、CD4+、CD8+细胞比较差异有统计学意义[(62.8±8.5)% 比(70.9±2.3)%、(33.3±7.0)% 比(39.8±1.8)%、(22.6±2.8)% 比(34.8±15.6)%,均P<0.05].(2)淋巴细胞亚群CD3+、CD4+及NK细胞比例随患儿儿童危重病例评分降低、第三代儿童死亡危险评分增高及器官功能障碍数目增多,呈明显下降趋势,差异有统计学意义(P<0.05),血清IgG、IgM、IgA及CD19+细胞变化差异无统计学意义(P>0.05).(3)死亡组患儿在入院24h内NK细胞及CD3+、CD4+细胞水平明显低于存活组[(1.5±0.5)% 比(4.7±1.4)%,(55.1±5.0)%比(66.4±7.4)%,(29.7±5.2)%比(35.0±7.2),均P<0.05].结论 未发现免疫球蛋白水平与严重脓毒症患儿病情严重程度有相关性;NK细胞及CD3+、CD4+淋巴细胞降低是脓毒症病情加重的标志,可作为评估严重脓毒症患儿预后的参考指标.     

Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: First results of ETA®

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC^® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.     

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孤独症谱系障碍(autistic-spectrum disorders,ASDs)近年来患病率逐年攀升至1%左右,其症状往往伴随终生,成为严重威胁儿童健康和发展的神经发育性疾患;注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)是儿童期最常见的精神障碍,国内报道患病率为4.13%～5.83%,其症状可延续至青少年期,甚至到成年期[1]。这两类精神障碍在成年期的临床表现、共患病、治疗策略和预后与儿童期有哪些不同呢?本文通过回顾相     

EXCITING NEW TREATMENT APPROACHES FOR PATHYPHYSIOLOGIC MECHANISMS OF SICKLE CELL DISEASE

During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.     

Infiltrations of Epstein-Barr virus-carrying cells in granular lymphocyte-proliferative disorders corresponding to chronic active Epstein-Barr virus infection

A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD) associated with chronic active Epstein-Barr virus (EBV) infection is described. Chromosomal analyses revealed several clonal abnormalities and two of them were mainly repetitious. High copy numbers of monoclonal EBV genome were also detected in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal expansion of EBV-infected LGLs. The patient had an indolent course for several years, and there was no evidence of infiltrations of his bone marrow until the end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype. The infiltrated LGLs showed latency I.     

LUTEINIZING HORMONE RECEPTOR MUTATIONS IN DISORDERS OF SEXUAL DEVELOPMENT AND CANCER

Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.     

Resurgence of measles in Singapore: profile of hospital cases

OBJECTIVE: To ascertain the profile of cases of measles seen at a general hospital during a recent outbreak that occurred despite a measles vaccination program. METHODOLOGY: A retrospective study from January 1991 to March 1998. All patients with measles (ICD code 055. 9) seen at the emergency unit or as inpatients were included. RESULTS: There were 87 cases identified. The diagnosis was clinical in all and proven serologically in 71%. Eighty-five per cent of the cases occurred between January 1997 and March 1998. There was a bi-modal age distribution with peaks in the very young (相似文献   

Personality profiles and heart rate variability (vagal tone) in children with recurrent abdominal pain

The aim of the study was to explore psychological factors and autonomic activity in children with recurrent abdominal pain and to compare them with those in a control group of healthy children. The Personality Inventory for Children was used for assessment of developmental, emotional and psychosocial factors in 25 children with recurrent abdominal pain (age, 7-15 y). Parasympathetic and sympathetic functions in these children and in 23 healthy control subjects (age, 7-13 y) were also investigated, non-invasively using a computerized polygraph. Vagal tone (parasympathetic function) was indexed by calculation of respiratory sinus arrhythmia in beats/min. Skin conductance (sympathetic function) was recorded by the constant current method. On the Personality Inventory for Children, 16 patients had high scores on somatic concern. Several patients had scores in the clinical range for depression, withdrawal and anxiety, but the mean scores for these personality profile scales were well within the normal range of healthy children. Interestingly, there was a spike on the L (Lie)-scale for most of the patients and 15 patients had scores above or close to the clinical cut-off value. As compared with the scores in healthy children, vagal tone and sympathetic tone were normal. Conclusion: Many children with recurrent abdominal pain have scores in the clinical range for depression, withdrawal, anxiety and L-scale indicating coping problems, denial and a trend towards somatic concern that may contribute to the evolution of abdominal pain. Autonomic nerve activity was not disturbed in these children.     

Overcoming surfactant inhibition with polymers

Inhibition of the function of pulmonary surfactant in the alveolar space is an important element of the pathophysiology of many lung diseases, including meconium aspiration syndrome, pneumonia and acute respiratory distress syndrome. The known mechanisms by which surfactant dysfunction occurs are (a) competitive inhibition of phospholipid entry into the surface monolayer (e.g. by plasma proteins), and (b) infiltration and destabilization of the surface film by extraneous lipids (e.g. meconium-derived free fatty acids). Recent data suggest that addition of non-ionic polymers such as dextran and polyethylene glycol to surfactant mixtures may significantly improve resistance to inhibition. Polymers have been found to neutralize the effects of several different inhibitors, and can produce near-complete restoration of surfactant function. The anti-inhibitory properties of polymers, and their possible role as an adjunct to surfactant therapy, deserve further exploration.     

Understanding infant formula

The World Health organisation recommends breast feeding infants for the first six months of life. When this breast feeding does not occur either through parental choice or medical need, infant formulas will be required. There is a bewildering array of formulas on the UK market for many different requirements. When faced with an unsettled infant many parents (and healthcare professionals) will experiment with the infant formula available and then attend the paediatric clinic looking for help and advice. It is therefore essential that paediatricians understand what milks are available and what the key differences between different products are. This review attempts to provide a simple guide through many of the formulations currently available in the UK; and offers advice for the dietary management of the child with extra calorie requirements, infants with cow's milk protein allergy, gastro oesophageal reflux disease, apparent unresolved hunger and infantile colic. Whatever the underlying condition, there is likely to be an infant formula that is suitable in this generation of ever expanding formulations.