再生障碍性贫血外周血Th1／Th2、Tcl／Tc2异常的临床意义

多数获得性再生障碍性贫血（简称再障）是T细胞介导的自身免疫性疾病。儿童再障强化免疫抑制治疗（intensive immunosuppressive therapy，IIST）有效率达71．8％，但至今未有明确的疗效预测指标。采用流式细胞术观察20例特发性再障儿童外周血辅助性T细胞（helper—T cell，Th）亚型（Th1、Th2）和细胞毒T细胞（cytotoxic—Tcell，Tc）亚群（Tc1、Tc2）水平，试图探讨Th1／Th2、Tc1／Tc2改变与病情、免疫抑制治疗（immunosuppressive therapy，IST）疗效的关系。     

Th1/Th2、Th17/Treg平衡与幼年特发性关节炎

CD40+T细胞在免疫防御中起了核心的作用.根据细胞的功能,迄今为止已经证明至少存在4种不同的CD4+T细胞亚群--Th1、Th2、Th17和调节性T细胞(Treg).幼年特发性关节炎(JIA)是常见的以慢性非化脓性关节炎为特征的自身免疫性疾病,主要由免疫网络失调引起,其中Th1/Th2细胞平衡、Th17/Treg细胞平衡发挥了重要作用.文章就Th1/Th2细胞、Th17/Treg细胞的分化、调节及Th1/Th2细胞失衡、Th17/Treg细胞失衡参与JIA发病的机制作一综述.     

儿童重型再生障碍性贫血Th1/Th2细胞相关因子表达研究

目的利用流式细胞术探讨儿童重型再生障碍性贫血(简称"再障")患儿体内Th1和Th2细胞相关因子白细胞介素-2(IL-2)、白细胞介素4(IL-4)、白细胞介素-10(IL-10)和干扰素-γ(IFN-γ)的变化特点。方法 2014年11月至2015年8月,在郑州大学第一附属医院诊治的30例初诊重型再障患儿,同时选择正常体检儿童20名为对照组,采取其静脉血,分别用流式细胞术测定所取血样标本中IL-2、IL-4、IL-10和IFN-γ的含量。并用独立样本t检验的统计分析方法分析两组儿重外周血中上述4种细胞因子的差异是否有统计学意义,用ROC曲线评价上述4种细胞因子对于诊断重型再障的临床意义。结果(1)重型再障患儿外周血中IL-2、IFN-γ浓度分别为7.56±5.93(pg/mL)、8.67±3.72(pg/mL),均高于对照组的4.45±2.94(pg/mL)、4.89±2.86(pg/mL),差异具有显著性(P0.05);IL-4、IL-10浓度分别为4.48±3.28(pg/mL)、9.00±3.60(pg/mL).均低于对照组的7.36±7.02(pg/mL)、10.93±5.13(pg/mL),但差异无显著性(P0.05)。(2)重型再障患儿外周血中IL-2 ROC曲线下面积(AUC)为0.746(95%CI 0.697~0.816),具有中度诊断价值;IL-4的AUC为0.662(95%CI 0.597~0.716),为低诊断价值;IL-10的AUC为0.616(95%CI 0.458~0.774),为低诊断价值;IFN-γ的AUC为0.817(95%CI 0.697~0.978),具中度诊断价值。结论 IL-2、IFN-γ为负调控造血因子,参与再障发病机制,但是Th1和Th2细胞相关因子(IL-2、IFN-γ和IL-4、IL-10)的表达水平高低,对于儿童获得性再障的诊断价值比较有限,     

Th1/Th2免疫应答失衡及其影响因素

辅助性T细胞(Th)1和2可分泌不同的细胞因子,具有不同的免疫功能,且二者的功能相互调节,处于一种平衡状态。母孕期的细胞因子向Th2型偏倚,以维持妊娠;孕母的营养,过敏都会改变胎儿的Th1/Th2平衡状态;胎儿出生后,随着接触不同的抗原,其免疫发育有其自身的特点。细胞因子对Th细胞的分化起着基本的调节作用;树突细胞、调节性T细胞等通过细胞因子网络影响Th1/Th2的平衡。该文就此作一综述。     

小儿外科脓毒症患儿Th1/Th2细胞免疫应答状况

目的 探讨外科治疗中严重腹腔感染脓毒症患儿Th1/Th2细胞免疫应答的变化规律.方法 选择本院收治的30例严重腹腔感染患儿为脓毒症组.同期门诊查体的30例健康儿童为健康对照组.脓毒症组(于术前和术后第1、5天)及健康对照组抽取空腹静脉血2 mL,采用双抗体夹心酶联免疫吸附法(ELISA)测定各组儿童血清IFN-γ和IL-4水平,计算IFN-γ/IL-4比值.采用SPSS 10.0软件进行统计学分析.结果 脓毒症组血清IFN-γ水平术前与健康对照组、术后第5天与术前、术后第5天与健康对照组比较,均无显著性差异(Pa>0.05);术后第1天与术前比较下降(t=6.083 P<0.01).脓毒症组血清IL-4水平术前与健康对照组、术后第1天比较均升高(t=11.65,1.996 Pa<0.01),与术后第5天比较下降(t=8.275 P<0.01),术后第5天与健康对照组比较仍高,未恢复至正常水平(t=3.453 P<0.01).脓毒症组IFN-γ/IL-4比值术前与健康对照组、术后第1天比较均明显降低(t=10.98,3.072 Pa<0.05),术后第5天与术前比较明显升高(t=6.417 P<0.01),但与健康对照组比较末恢复至正常水平(t=3.482 P<0.01).结论 严重腹腔感染脓毒症患儿Th1细胞应答减弱,Th2细胞应答增强,存在免疫抑制状态,手术打击加重Th1细胞向Th2细胞偏移,经手术干预、合理治疗,免疫功能可逐渐恢复.     

儿童急性ITP Th1/Th2细胞功能状态初步研究

目的探讨急性儿童特发性血小板减少性紫癜(ITP)Th1/Th2细胞功能状态及其在ITP免疫发病机制中的作用。方法采用流式细胞术胞内标记法检测外周血CD4+T细胞IL-4和IFN-γ阳性表达率;逆转录-聚合酶链反应(RT-PCR)及荧光定量PCR检测外周血CD4+T细胞中IFN-γ、IL-4、IL-5、IL-13、T-bet、GATA-3、SOCS-1、SOCS-3和TIM-3等Th相关的细胞因子及转录因子mRNA表达。结果①急性ITP患儿Th1细胞阳性率明显低于正常同年龄对照组(3.36%±1.25%vs12.71%±2.29%,P<0.01),Th2细胞比例明显升高(2.63%±1.35%vs0.46%±0.17%,P<0.01),Th1/Th2比值显著降低(1.45±0.57vs34.13±5.76,P<0.01);②急性ITP患儿GATA-3、SOCS-3mRNA表达明显增高,T-bet及SOCS-5表达与同年龄对照组无显著差异(P>0.05),TIM-3表达明显增高(P<0.01);③急性ITP患儿CD4+T细胞高表达Th2类细胞因子IL-4、IL-5、IL-13(P<0.01),Th1类细胞因子IFN-γ与正常对照比较无显著性差异(P>0.05)。结论急性ITP患儿Th2细胞过度活化,可能与ITP免疫功能紊乱有关。     

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.     

补充维生素D对佝偻病大鼠Th1/Th2细胞平衡的影响

目的 通过观察维生素D( VitD)缺乏性佝偻病大鼠在不同剂量VitD治疗前后免疫指标变化,探讨VitD对佝偻病大鼠Th1/Th2细胞平衡的影响.方法 选用21日龄SD大鼠32只,随机分为对照组(C组,n=10)、模型组(M组,n=10)和实验组(T组,n=12),T组又依据VitD治疗剂量不同均分为T1组(n=6)和T2组(n=6).T1组与T2组分别采用不同等级VitD一次性肌肉注射后行组间比较,观察幼鼠体质量、外周血碱性磷酸酶(AKP)、骨组织病理切片及外周血25-(OH)D3、IL-4、干扰素γ(IFN-γ)变化,并通过其外周血IL-4/IFN-γγ水平判断VitD对佝偻病大鼠Th1/Th2细胞平衡的影响.结果 缺乏VitD避光饲养30 d后,M组与T组的外观、骨组织病理切片较C组明显改变,其外周血AKP水平升高,同时血25-(OH)D3水平下降(Pa＜0.05).治疗后,T组较M组外观及病理切片有所好转,外周血AKP水平与25-(OH)D3水平明显改善(Pa＜0.05).免疫指标方面,血IFN-γ治疗前后的轻微波动均无统计学意义(Pa＞0.05),而外周血IL-4水平则在治疗后明显升高,且剂量越大,升高越明显(P＜0.05,0.01).结论 大剂量VitD可使机体Th1/Th2细胞平衡向Th2细胞移动,体内IL-4分泌增加,从而使机体处于易发生变态反应的状态.     

头孢呋辛对哮喘儿童外周血单个核细胞Th1/Th2平衡的影响

目的研究头孢呋辛对哮喘儿童外周血单个核细胞Th1/Th2平衡的影响。方法采用流式细胞术检测哮喘和健康儿童外周血单个核细胞IFN-γ和IL-4水平,以及哮喘儿童外周血单个核细胞经头孢呋辛体外干预后的IFN-γ和IL-4水平。结果与健康儿童相比,哮喘患儿外周血单个核细胞的IFN-γ和IFN-γ/IL-4比值降低,差异有统计学意义(P<0.05);哮喘患儿外周血单个核细胞在体外与头孢呋辛(100 mg/L)孵育48 h后,IL-4水平升高,差异有统计学意义(P<0.05),而IFN-γ的变化无统计学意义(P>0.05);IFN-γ/IL-4比值则降低,差异有统计学意义(P<0.01)。结论哮喘患儿外周血单个核细胞以Th2(IL-4)占优势,Th1/Th2比值平衡失调;而头孢呋辛更加剧这一倾斜,不利于哮喘治疗。     

反复呼吸道感染患儿T细胞功能性极化状态

目的观察反复呼吸道感染患儿间歇期外周血T细胞功能性极化状态。方法以反复呼吸道感染患儿外周血及健康儿童外周血为研究对象,采用全血PHA刺激培养,四色荧光标记流式细胞仪检测Th1(Tc1)及Th2(Tc2)百分比。结果反复呼吸道感染患儿Th1较正常降低(P<0.05),Th2升高、Th1/Th2比值下降(P<0.01);Tc1降低、Tc2升高、Tc1/Tc2比值下降(P>0.05)。结论反复呼吸道感染患儿间歇期存在Th功能性极化异常,Th2占优势;Tc功能性极化无明显异常。     

A new type of spondylo-metaphyseal dysplasia — Algerian type

A new, dominantly inherited, severe form of spondylometaphyseal dysplasia in five members of an Algerian family is reported. Another child, not investigated, was also probably affected. The disease is characterised by a unique clinical and radiological set of features: dwarfism, genu valgum deformity, progressive kypho-scoliosis, wrist deformity, myopia and severe metaphyseal dysplasia, with moderate spinal changes and minimal changes in the hands and feet. In view of the geographical localisation of the disorder and the anatomical distribution we propose the name Algerian type of spondylo-metaphyseal dysplasia.     

Vitamin D-dependent rickets type I and type II

Two distinct hereditary defects, vitamin D-dependent rickets type I (VDDR I) and type II (VDDR II), have been recognized in vitamin D metabolism. VDDR I is suggested to be a deficiency of the renal 25-hydroxyvitamin D (25(OH)D)-1α-hydroxylase. Muscle weakness and rickets are the prominent clinical findings. A normal physiologic dose of 1α-hydroxyvitamin D₃ and 1,25-dihydroxyvitamin D₃ is sufficient to maintain remission of rickets in this disorder. VDDR II consists of a spectrum of intracellular vitamin D receptor (VDR) defects and is characterized by the early onset of severe rickets and associated alopecia. This can be attributed to mutations in the VDR gene. Massive doses of vitamin D analogs and calcium supplementation is usually required for the treatment; however, the response to therapy is sometimes variable.     

A new type of spondylo-metaphyseal dysplasia--Algerian type. Report of five cases

A new, dominantly inherited, severe form of spondylometaphyseal dysplasia in five members of an Algerian family is reported. Another child, not investigated, was also probably affected. The disease is characterised by a unique clinical and radiological set of features: dwarfism, genu valgum deformity, progressive kypho-scoliosis, wrist deformity, myopia and severe metaphyseal dysplasia, with moderate spinal changes and minimal changes in the hands and feet. In view of the geographical localisation of the disorder and the anatomical distribution we propose the name Algerian type of spondylo-metaphyseal dysplasia.     

糖原累积病Ⅵ型和Ⅸa型7例病例报告并文献复习

目的总结糖原累积病(GSD)Ⅵ、Ⅸa型的临床、病理和基因突变情况,提高临床对这两型GSD的认识。方法回顾性收集GSD3例Ⅵ型和4例Ⅸa型患儿的临床资料。结果 (1)7例患儿均为男性,确诊年龄2岁3月至5岁。7例均有肝脏肿大和转氨酶升高,身材矮小1例,空腹低血糖、高乳酸血症和高甘油三酯血症各2例,血酮体增高3例,尿有机酸分析结果阳性2例。7例患儿均有肝细胞弥漫性肿大变形和糖原凝聚,4例有肝脏脂肪变性;3例GSDⅥ型有门管区纤维化、肝硬化表现。3例GSDⅥ型检测到6种PYGL基因突变,c.772+1GA、c.244-1GA、c.730CT(p.L244F)、c.2417_2418del TA(p.I806Sfs X9)为新突变,4例GSDⅨa型检测到4种PHKA2基因突变,c.3529CT(p.Q1177X)、c.3574CT(p.Q1196X)为新突变。(2)复习文献共检索到13篇文献,与本文病例合并后共22例Ⅵ型、99例Ⅸa型GSD。肝脏转氨酶增高和肝脏肿大91.9%~100%,有身材矮小18%~23%、空腹低血糖44%~48%、高甘油三酯血症37%~44%、高乳酸血症35%~72%和血酮体增高50%~56%。肝脏活检均可见肝细胞内糖原凝聚,17%有脂肪变性,Ⅵ型25%、Ⅸa型33%检出肝硬化。报道19种PYGL基因突变,多为点突变,剪切位点突变亦较常见,插入突变少见;43种PHKA2基因突变,突变类型多样。结论肝大伴转氨酶升高的患儿需警惕Ⅵ、Ⅸa型GSD;Ⅵ型患儿可早期存在肝硬化,需要进一步随访。     

Gaucher disease-norrbottnian type

We report follow-up studies of 22 cases of the Norrbottnian type of Gaucher disease (type III). The series was divided into 2 main groups of families depending on their birth province (Norrbotten, Västerbotten). The distribution and types of organ manifestations and complications were the same in both groups, each of which was considered to be genotypically homogeneous. The severity of the clinical symptoms and signs and the course of the disease differed markedly not only between families but also between siblings. Splenectomy accelerated deterioration, particularly with regard to skeletal and central nervous system manifestations. On a clinical basis it is concluded that the Norrbottnian type of Gaucher disease, which has now been diagnosed in about 40 cases, is probably due to a unique mutation which may have happened several hundreds of years ago in northern Sweden.Dedicated to Prof. Dr. H.-R. Wiedemann on the occasion of his 65th birthday     

Glycogenosis type I

OBJECTIVE: To o present up-to-date knowledge about Glycogen storage disease type I (GSD-type I) - a disease caused by the deposit of glycogen resulting from the deficiency of the enzyme glucose-6- phosphatase - and to provide the pediatricians with the necessary information for a precocious diagnosis and an adequate conduct for those cases where this metabolic disturbance is present. METHODS: Through Medline, the most significant articles published during the last 20 years were selected from national and international journals of medicine, with special attention to dietary treatment of glycogen storage disease type I. RESULTS: The metabolism of glycogen and the metabolic consequences of glycogen storage disease type I were discussed, especially hypoglycemia, the principal metabolic disturbance of the disease. The clinical and laboratory findings are described together with the histopathology. The use of uncooked cornstarch and enteral carbohydrate infusion are the means used for the maintenance of normoglycemia. The control of hyperuricemia, hyperlipidemia and platelet disorders are other aspects of the treatment as well as the prevention of infections and the use of G-CSF for glycogen storage type Ib. Hepatic transplant and its principal indications are commented on. Hepatic adenomae, which always have the potential of malignant transformation, are the results of incomplete treatment. CONCLUSIONS: Although it occurs rarely, glycogen storage type I is an important cause of volumous hepatomegaly which is associated with hypoglycemia among the infants. The dietary treatment of this illness has significantly altered the clinical course and has improved the prognosis. Therefore it is indispensable that the general pediatrician should be familiar with the diagnosis of this clinical state so as to act rigorously in favor of the dietary control.