先天性鱼鳞病样皮肤病变IPEX 1 例报告并文献复习

目的探讨X-连锁多内分泌腺病肠病伴免疫失调综合征(IPEX)的临床表型、治疗及预后。方法回顾分析1例以先天性鱼鳞病样皮肤病变起病的IPEX患儿临床资料,并复习相关文献。结果患儿,男,2个月11天,因鱼鳞样皮疹伴头部渗血、双足渗液就诊,合并重症感染及消化道穿孔,最终死于多器官功能障碍综合征。住院期间行全基因组外显子DNA检测,结果示FOXP3基因11号外显子c.1150GA,p.A384T半合子突变,其母亲为携带者,父亲无异常。结论早发顽固性腹泻、多发内分泌病及生长落后临床表型的婴儿需警惕IPEX,小婴儿出现鱼鳞样皮疹合并严重感染时,亦需排查IPEX,基因测序有助于确诊此病。     

X连锁多内分泌腺病肠病伴免疫失调综合征一例基因及蛋白表达研究

目的 探讨表现为顽固性腹泻、皮疹以及有或无胰岛素依赖性糖尿病的疑似X连锁多内分泌腺病肠病伴免疫失调综合征(IPEX)患儿FOXP3基因变异及其蛋白表达水平.方法 对近两年来我院收治的4例表现为早发性顽固性腹泻、皮疹以及有或无胰岛素依赖性糖尿病的疑似IPEX男性患儿进行FOXP3基因扩增及测序分析,将发现的可疑突变位点通过数据库查询及与100例健康儿童相同位点序列比较,采用流式细胞仪检测CD4~+CD25~+FOXP3~+调节性T细胞比例和FOXP3蛋白表达.结果 4例疑似患儿中发现1例FOXP3突变,为11号外显子66位碱基错义突变(G>A),导致FOXP3蛋白370位氨基酸由甲硫氨酸替换为异亮氨酸(Met370Ile),患儿母亲为携带者.100例正常儿童FOXP3基因相同位点未见变异,故可排除该位点多态性可能.该突变为此前未见报道的新突变,患儿CD4~+CD25~+FOXP3~+调节性T细胞比例升高而FOXP3表达量无减低.结论 通过临床、免疫学筛查和基因分析,发现我国首例IPEX患儿(g:13128 G>A c:1298 G>A Met370Ile),对早发胰岛素依赖性糖尿病、顽固性腹泻及不明肾脏损害婴幼儿,应考虑IPEX可能并进行FOXP3基因分析.     

脐血干细胞移植成功治疗早发IPEX综合征1例报告并文献复习

X连锁多内分泌腺病肠病伴免疫失调综合征(IPEX)是一种由FOXP3基因变异引起的原发性免疫缺陷病,典型表现包括严重肠病、1型糖尿病和湿疹三联征。患儿,男,以糖尿病、顽固性腹泻、湿疹、反复感染起病,经遗传学检测确诊为FOXP3基因变异引起的IPEX综合征,最终经脐血干细胞移植治疗,患儿自身免疫症状得到改善。对早发糖尿病、顽固性腹泻及湿疹婴幼儿,应考虑IPEX综合征可能并进行遗传学检测,早期造血干细胞移植可阻止大多数患儿的疾病进展和并发症的发生,提高患儿生存率。     

HCN1基因新生变异致Dravet综合征1例

目的探讨Dravet综合征临床及HCN1基因变异特征。方法回顾分析1例Dravet综合征患儿的临床资料及基因检测结果。结果 1岁11个月女性患儿,4月龄起病,表现为反复发热诱发的惊厥发作,发作时呈惊厥持续状态,发作形式多样。基因检测发现HCN1基因c.1199TC错义变异,导致第400号亮氨酸变异为脯氨酸(p.Leu400Pro);其父母该位点未见异常,为新生变异,尚未见报道。结论明确HCN1基因新生变异为致病基因,丰富了Dravet综合征的基因型。     

2日龄新生儿高胆红素血症合并血小板减少

患儿,女,生后2 d,因皮肤巩膜黄染半天入院。主要临床表现为持续严重的黄疸和血小板减少,最终确诊为先天性血小板减少性紫癜（TTP）。先后予光疗、输注新鲜冰冻血浆、红细胞、血小板及换血等治疗后,患儿病情好转。基因检测结果提示患儿ADAMTS13基因存在c.3650T > C (p.I1217T)纯合突变,其父母该位点均为杂合突变。先天性TTP是一种罕见的常染色体隐性遗传疾病,及时输注新鲜冰冻血浆可获得良好疗效。该病例为国内外首例报道该位点纯合突变所致的先天性TTP患儿。     

儿童原发性免疫缺陷病的临床特点

目的了解儿童原发性免疫缺陷病(PID)的临床特点,以助于早期识别和诊断。方法对本院儿科住院诊断为PID的26例病例进行回顾性分析,记录病史、出生史、家族史、临床表现、实验室检查、诊断、治疗和转归等情况。结果PID中选择性IgA缺乏症6例,普通变异性免疫缺陷病、婴儿暂时性低丙种球蛋白血症各5例,T、B细胞联合免疫缺陷病、湿疹血小板减少伴免疫缺陷综合征各4例,慢性肉芽肿病2例。25例临床表现为反复感染,感染部位主要是呼吸道和消化道;确定有条件致病菌感染6例,自身免疫性疾病5例,有家族病史6例。住院期间死亡、放弃治疗各1例,其他病情好转出院。结论对反复感染、条件致病菌感染或伴自身免疫性疾病患儿,结合家族史,应尽早行免疫学检查,以早期识别和诊断PID。     

高胰岛素血症伴高氨血症综合征1例报告并文献复习

目的探讨GLUD1基因变异所致高胰岛素血症伴高氨血症综合征临床表现和致病基因特点。方法回顾分析1例高胰岛素血症伴高氨血症综合征患儿的临床资料,并复习相关文献。结果女性患儿,1岁9个月起病,反复出现血糖偏低2年余,并惊厥发作3次,给予升血糖、止惊对症处理后可缓解;伴血胰岛素、血氨水平升高,诊断为高胰岛素血症伴高氨血症综合征。高通量测序发现患儿GLUD1基因存在错义变异c.965GA,p.Arg322His(杂合),其父母该位点均为正常基因型,为新生突变。结论基因检测有助于明确高胰岛素血症伴高氨血症综合征诊断。     

Wiskott-Aldrich 综合征1 例临床及基因分析

目的探讨Wiskott-Aldrich综合征(WAS)的WAS基因突变的特点。方法回顾分析1例WAS患儿的临床资料,以及利用PCR测序方法检测WAS基因全部外显子及侧翼序列。结果 5个月男性患儿,发现血小板减少入院,既往湿疹时间长且反复感染;CD8+及CD4+T淋巴细胞升高,CD 19+B淋巴细胞正常;骨髓细胞学提示巨核细胞成熟障碍。WAS基因检测发现存在C.880 AG(p.Ile294Val)突变,患儿父母均未见突变。利用Polyphen2软件及SIFT软件预测该位点为致病性突变,不同物种间序列保守性分析发现该位点保守;结构预测分析发现该位点突变可能会影响正常的蛋白结构,该突变国内外未见报道。结论基因检测可早期诊断WAS,新发现C.880 AG(p.Ile294Val)突变。     

LIG4基因突变导致慢性腹泻1例报告并文献复习

目的探讨LIG4综合征的发病机制和诊断。方法回顾分析1例LIG4综合征患儿的临床资料及基因检测结果。结果患儿,男,19个月,慢性腹泻病伴病毒、细菌和真菌混合感染;小头外貌,发育落后,营养不良;血常规示白细胞计数,尤其中性粒细胞和淋巴细胞数显著减少,T细胞和B细胞减少,考虑为免疫缺陷病。二代测序发现患儿存在LIG4致病基因的复合杂合变异,即错义突变c. 833 GT;p.Arg 278 Leu以及缺失突变c. 1271_1275 del, p.Lys 424 Argfs*20。结论慢性腹泻合并多重感染应警惕免疫缺陷病,基因检测有助确诊。     

拷贝数变异致高IgM综合征1例并文献复习

目的 探讨拷贝数变异致高IgM综合征的临床特征、免疫学特点及基因测序情况。方法 对1例拷贝数变异致高IgM综合征患儿的临床、实验室及遗传资料进行分析,并检索拷贝数变异所致高IgM综合征的相关文献。结果 患儿男,生后反复感染,伴黄疸及门静脉海绵样变性,血IgG及IgA下降,血中性粒细胞减少。父母非近亲结婚,无阳性家族史。高通量测序常规生物信息分析未发现致病突变,拷贝数变异分析示CD40LG基因大片段缺失,DNA样本CD40LG基因1-5号外显子PCR无扩增,cDNA扩增无产物。流式细胞术检测淋巴细胞CD40L蛋白表达缺如。文献检索结果显示,高IgM综合征以点突变最为多见,CD40LG、AICDA基因存在拷贝数变异报道。结论 拷贝数变异与点突变所致的高IgM综合征临床表现、免疫学指标无明显差异。对临床可疑高IgM综合征但二代测序未发现致病突变的病例需进行拷贝数变异分析。     

Gene polymorphisms in childhood ALL

Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children. Inherited predisposition and exposure to exogenous leukemogenic agents have been investigated as potential risk factors. Current therapy results in 5-year event-free survival exceeding 80% in children in developed countries. Predisposition to ALL and event-free outcome seems to be influenced by polymorphisms on genes involved in several metabolic pathways. The purpose of this review is to discuss the findings of different studies upon the role of gene polymorphisms in childhood ALL.     

儿童免疫性血小板减少症发病机制研究进展

免疫性血小板减少症(immune thrombocytopenia,ITP)是一种由自身免疫介导的出血性疾病,其特点为血小板破坏增多和生成不足.ITP发病机制复杂多样,具有异质性,至今尚未完全明确,在儿童中尤其突出.现有研究表明,免疫失耐受引起各种免疫细胞或分子异常,进而导致血小板破坏增多或生成不足,是ITP的核心发病...     

Retrospective evaluation of children with immune thrombocytopenic purpura and factors contributing to chronicity

ObjectiveImmune thrombocytopenic purpura (ITP) is the most common cause of acquired thrombocytopenia children. The aim of this retrospective study is to describe presenting features and clinical characteristics of ITP and evaluate clinical course, treatment modalities, and complications and determine the effects of preceding infection history, age, gender, treatment modality, and admission platelet count on chronicity.MethodTwo hundred and eleven patients who were diagnosed ITP and followed-up in Department of Pediatric Hematology, Ankara Children Hematology Oncology Education and Research Hospital between January 2008 and September 2012 were included. Age of the patients, gender, date of admission, date of diagnosis, complaint in the application, previous infection and laboratory tests were recorded.ResultsMean age of the patients on diagnosis was 5.4 ± 4.1 years. The female/male ratio was 1.03. The clinical courses were determined as acute or chronic in 72% and 28% of patients respectively. Mean age at diagnosis was significantly higher in chronic ITP (p < 0.01). Chronic course was significantly higher in female patients (p < 0.05). The most frequent complaint was bruises on the skin (68%). The most common physical examination findings were petechiae, purpura and ecchymosis (89%). Patients with a history of past infection (53.6%) and who had serologically positive infection (15.6%) frequently had acute course (p < 0.01). The most common serologically positive infection was Rubella. The mean platelet count was significantly higher in chronic ITP (p < 0.01). In the initial treatment of patients admitted in the acute phase, megadose methylprednisolone (MDMP) was used in 31% of patients, intravenous immune globulin (IVIG) in 55% of patients and anti-D in 2% of patients while 12% did not receive any treatment. There were no significant differences between the recurrence rate and treatment modality (p > 0.05).ConclusionIn our study, in females and in patients without any history of past infection, platelet count >20 × 10⁹/L and initial diagnosis age > 10 years were found to increase the probability of chronic disease, which is compatible with the literature.     

Toll样受体在小儿轮状病毒感染中的研究进展

Toll样受体是识别病原体病原相关分子模式的受体,是天然免疫和获得性免疫的桥梁,Toll样受体通过识别病原体,激活天然免疫,诱导产生多种细胞因子,影响初始T细胞的分化,目前认为识别轮状病毒和抗轮状病毒天然免疫反应有密切关系的Toll样受体主要有TLR2、3、4、7、8、9.该文就Toll样受体在轮状病毒感染机体中的发病机制及在预防轮状病毒感染及控制炎症反应中的作用作一综述     

Plasma‐mediated immune suppression: a neonatal perspective

Plasma is a rich mixture of immune regulatory factors that shape immune cell function. This immunomodulatory role of plasma is especially important in neonates. To maintain in utero feto‐maternal tolerance and to allow for microbial colonization after birth, the neonatal immune system is biased against pro‐inflammatory responses while favoring immune suppression. Therefore, the neonatal period provides a unique opportunity to study the physiologic mechanisms regulating the immune system. Several recent studies in neonates have identified plasma factors that play a key role in immune regulation. Insight into immune regulation by neonatal and adult plasma may have clinical implications, because plasma is easily accessible, affordable, and widely available. Herein, we review plasma‐mediated immune regulation, with specific focus on neonatal plasma. We discuss how immune suppression is a key function of plasma and provide a systematic overview of the published literature regarding plasma‐derived immune suppressive proteins, lipids, purines, and sugars. Finally, we outline how immune regulation by these factors, which are particularly abundant in neonatal plasma, may eventually be used to treat immune‐mediated diseases, such as autoimmune, allergic, and inflammatory diseases.     

Hypogammaglobulinemia: Incidence, risk factors, and outcomes following pediatric lung transplantation

Abstract:  Infection is the leading cause of morbidity and mortality in the first year following lung transplantation. HG after adult lung transplantation has been associated with increased infections and hospitalization as well as decreased survival. The purpose of this study is to define the incidence, risk factors, and outcomes of HG in the first year following pediatric lung transplantation. A retrospective review of all lung transplant recipients at a single pediatric center over a four-yr period was performed. All serum Ig levels drawn within one yr of transplantation were recorded. An association between HG during the first year after transplantation and age, race, gender, diagnosis leading to transplantation and clinical outcomes including hospitalization, infections requiring hospitalization, viremia, fungal recovery from BAL lavage, and mortality was sought. HG was defined using age-based norms. Fifty-one charts were reviewed. Mean (±s.d.) post-transplantation levels for IgG, IgA, and IgM were 439.9 ± 201.3, 82.3 ± 50.2, and 75.2 ± 41.4 mg/dL, respectively. HG was present in 48.8%, 12.2%, and 17.1% of patients for IgG, IgA, and IgM, respectively. Patients with HG for IgG were older (14.3 ± 3.8 vs. 9.2 ± 5.4 yr; p < 0.01). IgA and IgM HG were associated with invasive aspergillosis (p < 0.01 and p = 0.05, respectively). IgG and IgM levels inversely correlated with bacterial infections and hospital days, respectively (p < 0.01, p < 0.05). HG is a frequent complication following pediatric lung transplantation. Low Ig levels are associated with increased infections and hospital stay.     

On the influence of age on immunity in Down's syndrome

In 23 subjects of different ages with Down's syndrome a number of parameters of non-specific defense of humoral and of cellular immunity were investigated. While in all age groups complement factors C₃, C₄ and C₅ as well as phagocytosis and NBT indices were in the normal range, a dysgammaglobulinaemia increasing with age with a hyperglobulinaemia of the IgG, IgA and IgD types was found, sparing immunoglobulins IgM and IgE. In addition the transformation capacity of peripheral blood lymphocytes decreased with age. This is understood as the consequence of premature aging of the thymus-dependent immune system.