IgG亚类与支气管哮喘

IgG亚类的缺陷可导致严重的支气管哮喘。IgG_4在哮喘的发病和治疗过程中,既具有过敏性抗体的特性,又具有封闭抗体的作用。本文介绍了IgG 4种亚类的生物特性,以及它们和IgA、IgE在支气管哮喘中的作用机理及调节。     

细胞因子与支气管哮喘的研究进展

细胞因子（cytokinesCKs）是细胞释放的肽类介质,能调控细胞的生长与分化,起着细胞间相互调控作用。支气管哮喘是一种由多种细胞、细胞因子和炎症介质引起的、以气道高反应性为特征的变态反应性炎症性疾病。细胞因子在哮喘的炎症形成中起重要作用。按其对炎症形成的影响,可分为两大类：一类是以促炎作用为主的因子,如白介素（IL）回～9、11～15、a肿瘤坏死因子（TNF－a）、粒细胞巨噬细胞集落刺激因子（GM－CSF）、血小板活化因子（PAF）等。它们主要由活化的T辅助细胞释放,在哮喘的免疫病理过程中起重要作用。另一类则是以抑炎…     

支气管哮喘患儿吸入糖皮质激素治疗前后细胞因子及免疫功能变化

目的　探讨支气管哮喘患儿吸入糖皮质激素前后细胞因子、T细胞亚群等指标的变化。方法　采用双抗体夹心ELISA法检测 2 8例哮喘患儿吸入糖皮质激素前、吸入 1个月、吸入 1年后血清白细胞介素 6 (IL 6 )、IL 8、肿瘤坏死因子α(TNF α)水平 ,同时检测外周血T细胞及其亚群、B细胞变化。结果　哮喘患儿吸入前血清IL 6、IL 8、TNF α均显著高于正常对照组 (P <0 .0 1)。吸入 1个月、1年时 ,3种细胞因子水平渐降低 ,但仍高于正常水平。哮喘患儿外周血CD3+ 、CD4 + 、CD8+ 细胞均显著低于正常对照组 ,而CD4 + /CD8+ 、B细胞下降 ,但仍未降至正常水平。结论　哮喘患儿存在多种细胞因子失调及T细胞亚群、B细胞失衡。IL 6、IL 8、TNF α可能参与哮喘的炎症反应。吸入糖皮质激素可显著降低体内炎症细胞因子水平 ,促进T细胞亚群恢复平衡     

支气管上皮在哮喘发病中的作用

传统认为支气管上皮仅仅是构成气道内外环境的生理屏障,通过其粘液纤毛系统和机械屏障作用在气道防御中起重要作用。近年来随着对哮喘发病机制的深入研究,对上皮在气道疾病尤其是哮喘中的作用已经形成新的认识,即支气管上皮通过分泌炎症介质、细胞因子和生长因子等主动参与哮喘的气道炎症和重塑过程,并与哮喘的病理生理表现如气道阻塞和气道高反应密切相关,可概括为以下几方面。     

神经生长因子在支气管哮喘发病机制中的作用

神经生长因子(NGF)是最早发现的神经营养因子之一,来源于多种免疫细胞及肺固有细胞,对多种免疫细胞具有调节作用.近年来研究认为NGF可能在支气管哮喘的发病机制中扮演重要角色.该文综述了NGF的来源细胞及其在调节支气管哮喘的气道炎性反应、气道高反应性及气道重塑中的作用.     

哮喘患儿T细胞亚群及细胞因子的变化

哮喘发病机理方面的研究已成为当今哮喘的研究热点。目前认为Ｔ细胞的激活及其释放的细胞因子在哮喘的发病中起着重要作用。关于哮喘患者的Ｔ细胞亚群改变 ,各家报道结果不一。现将我们观察的结果报告如下。对象1998年 1月～ 1999年 1月间在我院诊断为支气管哮喘的患儿 38例 ,均符合全国儿科哮喘协作组制定的哮喘诊断标准[1] 。发作期 38例 ,其中男 2 9例 ,女 9例 ;平均年龄 (8±4)岁 (2～ 14岁 )。其中有 2 7例缓解期时第 2次采血 ,距第 1次采血时间间隔为 (2 0± 3)ｄ。对照组 2 0例 ,均为我院同期门诊体检正常儿童 ,其中男 14例 ,女 6例 …     

骨髓造血祖细胞在支气管哮喘发病中的作用

近年来的研究发现,支气管哮喘(简称哮喘)的发病不单单局限于气道和肺组织,还存在一个全身性的反应机制,而骨髓造血祖细胞等在哮喘发病中的作用日益受到重视。哮喘发病过程中,不仅骨髓内祖细胞增多,核糖体顺反子表达增高,而且外周血循环及局部肺组织中造血祖细胞也增多。白细胞介素-5,9,12和嗜酸性细胞趋化因子参与了这一过程。通过研究骨髓造血祖细胞等在哮喘中的作用,人们正试图寻找哮喘治疗的新途径。     

Serum immunoglobulins and immunoglobulin G subclasses with recurrent wheezing

In this study serum immunoglobulins (Ig) and IgG subclasses were measured in 42 patients (ranging 9 month-6 year) with recurrent wheezing and in 37 healthy children determined the relationship between serum Igs and recurrent wheezing. Patients were divided into two groups according to the age [9 month-2 year (n: 15), and 2–6 year (n: 27)]. In the patients placed in 9–24 month age group, serum lgG₄ level was found to be lower than controls (p<0.05). But there was not a significant difference in mean serum concentrations of total IgG, IgA, IgM, IgE, IgG₁ lgG₂ and lgG₃ subclasses between the groups (P>0.05). In the 25 month-6 year age group the mean IgE level was increased compared to the control while lgG₃and lgG₄ levels were decreased (p<0.05). On the other hand, in the 9–24 month age group there was no significant difference between the patients and controls for IgG subclasses deficiency (P>0.05). However, significant difference in IgG subclasses deficiency was present between the patients and controls in the 25 month-6 year group (P<0.001). In conclusion, our findings suggest that wheezing in childhood may be associated with low lgG₃and /or lgG₄, and in older children high IgE level may be a part of pathogenetic mechanism in patients with recurrent wheezing.     

Serum immunoglobulin G subclasses and serum immunoglobulin A in acute bronchiolitis in infants

Serum IgG subclasses and Serum IgA were studied in 43 infants with acute bronchiolitis and 20 healthy infants. IgG subclasses were determined by a capture ELISA and IgA was quantified by turbidimetry. IgG1 concentrations were significantly lower in infants with bronchiolitis than in normal infants. The other IgG subclasses and IgA did not differ between the groups. The subgroups of infants with bronchiolitis who had previously suffered from otitis media or bronchitis, had significantly lower IgG2 than the other infants with bronchiolitis. The same was found for infants with bronchiolitis who had suffered from three or more lower respiratory tract infections. In infants who had suffered from upper or lower respiratory infections before the acute bronchiolitis, IgA was significantly higher than in infants without previous respiratory infections. Ten infants with bronchiolitis (23%) had IgGl deficiency, that is values below the lower reference limit calculated in a population of healthy Norwegian infants. No healthy infants had any IgGl deficiency. No infant with bronchiolitis had IgG2 or IgG3 deficiency. The low IgGl values found in infants with acute bronchiolitis, may be one cause for infants to be more susceptible to RS virus infections.     

母体IgG对NMDA诱导的其幼鼠海马神经元损伤的保护作用的研究

目的研究母体免疫球蛋白G（immunoglobulin G,IgG）对N甲基D天冬氨酸（N-methyl-D-aspartate,NMDA）诱导的其幼鼠海马神经元损伤的作用及机制。方法通过体外幼鼠海马神经元原代培养,观察海马神经元在NMDA神经毒性作用下的变化,以及给予不同浓度的母体IgG后的影响。通过测定神经元漏出的乳酸脱氢酶（lactic dehydrogenase,LDH）活力,观察神经元损伤情况,用锥虫蓝染色观察细胞死亡率。结果体外神经毒性损伤后,培养神经元漏出的LDH较NMDA处理前和正常对照组高（P〈0．01）;给予不同浓度的母体IgG（分别为10mg／L、100mg／L）后,LDH漏出较NMDA组低（均P〈0．01）,而且较大剂量比小剂量的保护作用更为显著（P〈0．05）。锥虫蓝染色显示NMDA组神经元死亡率较NMDA处理前和正常对照组高（P〈0．01）;给予不同浓度的母体IgG（分别为10mg／L、100mg／L）,死亡率均比NMDA组低（P〈0．05、0．01）,而且较大剂量比小剂量的保护作用更强（P〈0．05）。结论体外幼鼠海马神经元原代培养结果表明,50μmol／L NMDA可诱导幼鼠海马神经元损伤,母体IgG对NMDA的神经毒性有保护性作用,而且有剂量依赖关系。     

Reduced levels of IgG subclasses and IgA in young children with asthma

Serum immunoglobulins including IgG subclasses were measured in 73 unselected children with asthma. The results showed that 22 (30%) had partial IgA and/or IgG₄ subclass deficiency. Clinical assessment showed that 21 children were infection-prone, and 52 were not. Further analysis showed that infection-prone children were significantly different from non-infection-prone children with regard to familial history of allergy (29% vs 60%, p = 0.015), elevated IgE (62% vs 33%, p = 0.021), IgA deficiency (38% vs 15%, p = 0.38) and IgG subclass deficiency (24% vs 4%, p = 0.018). These results suggest that there may be subgroups of children with asthma who are also immunodeficient.     

The effect of asthma and its treatment on growth

Asthma has little, if any, significant effect on attained adult height. Untreated asthma results in a delay of puberty by approximately 1.3 years, and pubertal delay is likely to explain the majority of apparent growth failure in asthmatics. All currently available inhaled corticosteroids (ICS) result in growth suppression at conventional doses (400 microg/day of beclomethasone dipropionate equivalent), but the growth suppressive effects are relatively short lived, after which growth reverts to pretreatment levels. Younger, prepubertal children, appear more sensitive to the growth suppressive effects of ICS. Asthmatic children receiving conventional doses of ICS (400 microg/day of BDP equivalent) will attain an adult height indistinguishable from their predicted adult height (based on their mid parental height), and no different from non-asthmatics. Adult height could possibly be decreased in severe asthmatics, but this is unlikely to be greater than a 1.2 cm decrement. Recent longitudinal studies offer reassurance that at conventional doses ICS do not have significant long term effects on growth, and that their benefits consistently outweigh their side effects.     

哮喘患儿体重指数与血清炎性因子水平对哮喘控制的影响

目的探讨哮喘患儿体重指数(BMI)及血清炎性因子水平对哮喘控制的影响。方法依据BMI结果将2013年1月至2014年5月收治的116例哮喘患儿分为正常组(n=59)、消瘦组(n=31)与肥胖组(n=26),ELISA法检测各组患儿白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平,免疫比浊法检测各组高敏C反应蛋白(hs-CRP)水平。治疗4周后采用儿童哮喘控制测试(C-ACT)评价各组患儿哮喘控制情况。结果 IL-6、hs-CRP及TNF-α在正常组、消瘦组及肥胖组水平依次增加(P0.05),C-ACT评分在正常组、消瘦组及肥胖组逐渐降低(P0.05);正常组完全控制率、部分控制率与未控制率均显著优于消瘦组与肥胖组(P0.05),但消瘦组与肥胖组间比较差异均无统计学意义(P0.05);IL-6、hs-CRP及TNF-α与C-ACT评分均呈负相关(P0.05),C-ACT评分、IL-6、hs-CRP、TNF-α与BMI均无相关性(P0.05)。结论 BMI过高或过低时,血清炎性因子水平均升高,不利于哮喘控制,哮喘患儿维持正常体重有利于降低血清炎性因子水平,提高哮喘控制率。     

The effect of asthma and its treatment on growth.

Asthma has little, if any, significant effect on attained adult height. Untreated asthma results in a delay of puberty by approximately 1.3 years, and pubertal delay is likely to explain the majority of apparent growth failure in asthmatics. All currently available inhaled corticosteroids (ICS) result in growth suppression at conventional doses (400 microg/day of beclomethasone dipropionate equivalent), but the growth suppressive effects are relatively short lived, after which growth reverts to pretreatment levels. Younger, prepubertal children, appear more sensitive to the growth suppressive effects of ICS. Asthmatic children receiving conventional doses of ICS (400 microg/day of BDP equivalent) will attain an adult height indistinguishable from their predicted adult height (based on their mid parental height), and no different from non-asthmatics. Adult height could possibly be decreased in severe asthmatics, but this is unlikely to be greater than a 1.2 cm decrement. Recent longitudinal studies offer reassurance that at conventional doses ICS do not have significant long term effects on growth, and that their benefits consistently outweigh their side effects.     

支气管哮喘患儿T淋巴细胞及细胞因子的变化

为观察儿童支气管哮喘时Ｔ淋巴细胞亚群分布以及Ｔ细胞活化相关因子及受体的表达状况，应用放射免疫分析等技术，对３４例发作期、２５例缓解期支气管哮喘患儿和１５例正常对照的外周血Ｔ淋巴细胞亚群、血浆及淋巴细胞膜表面白细胞介素－２受体（ＩＬ－２Ｒ）和相关细胞因子等水平进行系统检测。结果：（１）发作期患儿外周血Ｔ细胞亚群ＣＤ３，ＣＤ４及ＣＤ４／ＣＤ８值与缓解期患儿及正常对照比较差异无显著意义，但发作期ＣＤ８高于正常对照（Ｐ＜０．０１）和缓解组（Ｐ＜０．０１）；（２）发作期患儿血浆可溶性ＩＬ－２Ｒ、（ｓＩＬ－２Ｒ）、ＩｇＥ水平明显高于缓解期患儿和正常对照（Ｐ＜０．０１）；（３）免疫电镜观察显示，发作期患儿淋巴细胞膜表面ＩＬ－２Ｒ表达高于正常对照（Ｐ＜０．０５）。提示：（１）哮喘患儿外周Ｔ淋巴细胞亚群的分布发生了变化，哮喘发作期Ｔ淋巴细胞处于激活状态；（２）血浆ｓＩＬ－２Ｒ、ＩｇＥ水平与哮喘病情变化密切相关，可作为临床哮喘病情监测的指标。     

Role of immunoglobulin subclasses and specific antibody determinations in the evaluation of recurrent infection in children.

We studied humoral immune function in 267 children with recurrent respiratory infections referred to our immunology clinic to determine the most appropriate immunologic studies for evaluating recurrent infections in children. Of this highly selected population, 58% had a partial deficiency in one or more of the major immunoglobulin isotypes or IgG subclasses (defined as at least 2 SD below the normal age-adjusted mean). In none of the patients was there a total absence of an immunoglobulin isotype. The most common abnormality was partial IgA deficiency, which was found in one third of the patients. Twenty-six patients had only partial IgG subclass deficiencies, of which 20 were deficiencies of a single subclass. IgG1 was an isolated partial defect in three patients, IgG3 in five patients, and IgG2 and IgG4 were selective partial defects in six patients each. Tetanus toxoid and pneumopolysaccharide type 3 were the most immunogenic of the immunogens tested; hyporesponsiveness to pneumococcal polysaccharide types 7, 9, and 14 was common. Nineteen percent of the patients with normal immunoglobulin concentrations who were tested had lower-than-expected antibody titers; 42% of those tested with partial isotype deficiencies had deficient antibody responses. Of 25 patients with selective partial IgG subclass deficiencies or combined IgG subclass deficiencies, eight had antibody deficiencies. Our findings indicate that a high proportion of children referred to immunology clinics for recurrent infection have a demonstrable immunologic abnormality. Selective IgG subclass deficiency or a combined IgG subclass deficiency without an associated deficiency in a major immunoglobulin isotype is unusual. Identification of such patients is not predictive of the capacity to form antibodies to the antigens tested in this study and, in our opinion, adds little to the initial evaluation of immune function in such children.