原发性免疫缺陷病早期识别

原发性免疫缺陷病(primary immunodeficiency disease,PID)是一类以单基因遗传为主的少见免疫缺陷疾病。国外流行病学研究认为,具有临床表现的PID发病率为1/20000～1/5000活产婴。我国目前仅有极少部分PID患儿得到确诊,早期诊断是提高PID患儿生存率和生活质量的关键。本文首先分析国外PID预警症状在PID诊断中的价值,然后根据笔者单位多年来积累的临床经验,结合我国国情,提出PID早期识别线索,以供儿童免疫专科医师讨论和儿科医生参考。     

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1免疫缺陷病原发性免疫缺陷病(PID)的临床筛查工作已在我国部分地区开展,但全国范围内新发病例仍很少,提示儿科医师尚应加强警觉,逐步在相对发达地区基层医院建立免疫缺陷病初筛手段。PID是免疫学研究的天然模型,疾病相关基因的突变与表现型的关系对阐明靶基因的功能十分重要。随着PID病例逐渐累积,将可能在今后数年提供中国大陆PID基因突变特点与疾病表现的初步数据。重庆医科大学儿童医院分析了9例Wiskott Aldrich综合征患儿,发现其中4例患儿存在3种新型突变,但所有患儿均具有典型临床表现,扫描电镜检测其淋巴细胞异常亦相似[1]。其…     

小儿过敏性和免疫性疾病诊断治疗进展

1　原发性免疫缺陷病 (PID)已明确的PID达到 12 0种以上 ,随着分子遗传学的快速发展 ,每年都有大约 10种新的PID被发现。儿科医生对PID认识能力和实验室诊断技术的提高 ,也使检出率明显增高。国内PID的报道较以往增多 ,一些误诊为其他疾病者 ,经分子生物学技术可得以确诊。有报道 3例WASP基因分析确诊的湿疹血小板减少伴免疫缺陷 (WAS)患儿中 ,有 1例轻型患儿仅有血小板减少 ,而被长期误诊为特发性血小板减少性紫癜即是典型的例子。国内首次报道 1例Ⅰ型白细胞粘附分子缺陷病 (LAD I) ,患儿白细胞缺乏粘附分子CD18,中性粒细胞不…     

原发性免疫缺陷病早期筛查技术进展

原发性免疫缺陷病(PID)是一类由于单基因突变导致免疫细胞、免疫分子数量异常和/或功能缺陷的疾病。PID患者易反复感染, 伴过敏、自身免疫、自身炎症和恶性肿瘤性疾病, 疾病的致死、致残率极高, 早期诊断和治疗有助于改善预后。目前已知的PID筛查技术包括T淋巴细胞受体剪切环筛查重症联合免疫缺陷病, Kappa重排剪切环筛查无丙种球蛋白血症, 串联质谱法筛查腺苷脱氨酶缺陷和嘌呤核苷磷酸化酶缺陷, 蛋白组学筛查特定的蛋白缺陷以及二代测序技术筛查基因变异。现就目前PID的早期筛查技术进行简要总结, 为日后我国筛查工作的开展提供参考。     

原发性免疫缺陷病的分类及发病环节

原发性免疫缺陷病(Primary immunodeficiency disease, PID)是一组因免疫活性细胞的发生、分化或相互作用的复杂系统有先天性的缺损,而造成机体免疫功能低下的疾病。广义而言,PID应包括特异性和非特异性的免疫缺陷病,前者包括B细胞介导的体液免疫和T细胞介导的细胞免疫缺陷,后者包括吞噬细胞和补体的缺陷。狭义的PID,则专指特异性免疫缺陷病(SPID),即淋巴细胞介导的免疫缺陷,本文的内容仅限此范畴。     

原发性免疫缺陷病的诊断与治疗进展

原发性免疫缺陷病(PID)是一类主要以单基因遗传为主的少见免疫缺陷疾病,2007年发表的新版PID分类纳入了一些以免疫失衡和自身炎性反应为主要表现的PID。其诊断除仍应强调临床和免疫功能初步筛查外,部分疾病的分子诊断、快速诊断和功能学诊断也有了较大进展。近半数PID需免疫重建治疗,规范合理的开展造血干细胞移植是挽救患儿生命的关键。现就PID的诊断治疗进展作简要介绍。     

原发性免疫缺陷病感染防治措施概述

原发性免疫缺陷病（PID）患儿易发生反复、严重、持续或致死性感染。熟悉PID感染防治措施有利于对这类疾病患儿进行慢病化管理及改善预后。本文主要介绍PID感染防治措施中的一般措施、疫苗接种、抗生素应用及静脉注射丙种球蛋白替代治疗。     

小儿免疫及原发性免疫缺陷病

072870儿童过敏性和免疫性疾病的临床研究进展/赵晓东…∥中国实用儿科杂志.-2007,22(5).-345～347072871高效抗逆转录酶病毒疗法治疗小儿获得性免疫缺陷综合征:附95例临床报告/谢丽珊…∥中国小儿急救医学.-2007,14(2).-162～163监测95例获得性免疫缺陷综合征患儿接受治疗前后血浆病毒载体及CD4+T淋巴细胞计数,评价生长发育状况,并观察药物不良反应。结果:绝大多数患儿在治疗后3个月时血浆病毒载量达到阴性水平,CD4+T淋巴细胞计数达25%以上,药物不良反应较少。参3(林榕)072872大气污染对沈阳市6～8岁儿童免疫功能的影响/朱晓敏…∥中国…     

原发性免疫缺陷病临床发病情况回顾

目的了解原发性免疫缺陷病的临床发病情况,加强临床医师对该类疾病的认识,促进今后防治工作的开展.方法回顾性分析1974年1月至2003年12月我院93例原发性免疫缺陷病患儿的临床资料.结果93例原发性免疫缺陷病患儿中,以抗体缺陷为主者占39.8%（37/93）;以联合免疫缺陷者占22.6%（21/93）;以T淋巴细胞缺陷为主者占14.0%（13/93）;其他明确的免疫缺陷综合征者占12.9%（12/93）;吞噬功能缺陷者占9.7%（9/93）;补体缺陷者占1.1%（1/93）.从年度诊断的原发性免疫缺陷病病例数来看有逐年增多的趋势,1996年以后诊断例数呈现大幅度上升,共诊断50例.死亡病例共计16例,以联合免疫缺陷病为主.男：女=3：1.结论我国各类原发性免疫缺陷病均有发病,并且随着诊断技术水平的不断提高,临床诊断的病例日益增多,已成为临床,特别是儿内科的一组重要的疾病,应引起全国临床医师的注意.     

新生儿原发性免疫缺陷病筛查进展

原发性免疫缺陷病(PID)是严重影响儿童生命健康的疾病,尽早识别、及时干预是改善预后的关键。部分PID在新生儿期即出现临床警示症状,然而由于PID种类繁多,早期识别PID仍存在巨大挑战。目前已经有基于干血纸片的PID筛查手段,包括TREC筛查SCID及其他T淋巴细胞减少性疾病,KREC筛查XLA及其他B细胞减少疾病,多...     

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.     

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   

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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.     

A profile of respiratory symptoms in urban and rural South Australian school children

This report describes the cross-sectional analyses of data from the first year of a longitudinal study using questionnaire and respiratory function data over a 5 year period from a sample of rural South Australian school children. The cumulative or lifetime prevalences of respiratory symptoms were estimated in 825 rural and 1261 urban school children aged between 5 and 15 years in order to determine if the prevalence rates differed between rural and urban school children. The study found the overall cumulative prevalence of asthma and/or wheezy breathing (AWB) to be 24.1% in the rural school children compared to 27.6% in the urban school children. Most children developed AWB symptoms before the age of 7 years, with 20% reporting moderately severe symptoms and 10% having more than one attack per fortnight. The cumulative prevalence of bronchitis, loose/rattly cough (BLRC) differed significantly between the rural school children (34.1%) and urban school children (47.9%). The BLRC symptoms preceded the development of AWB in many cases. Urban school children also reported a higher prevalence of atopic conditions.     

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.     

Hauttemperaturen verschiedener Körperoberflächenareale des Rumpfes bei Säuglingen

Summary In two groups of infants (3–53 weeks old) skin temperatures were controlled in different areas of the trunk—i.e.: regions of sternum, lungs, heart, liver, spleen, kidneys—at different room-temperatures (group I: 21–25°C; group II: 29–32°C). Rectal temperatures of some probands in both groups also had been controlled simultaneously. A definite change in the reaction to heat was proofed in different periods of the first year of life. In higher environmental temperatures the skin temperature was almost constant at every controll-point of the skin, even in older infants. In lower environmental temperatures the skin temperatures lowered continuously with age till 7. to 9. moth. From 10. to 12. month the lowering of skin temperature discontinued. The rectal temperatures were relatively constant in all infants. Only in infants from 7. to 12. month, whose skin temperatures were controlled in lower as well as in higher environmental temperatures, a tendency to higher rectal temperatures was proofed in warmer environmental temperatures.The significance of these results is discussed.

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Untersuchungen mit Unterstützung durch die Deutsche Forschungsgemeinschaft.