Serum immunogiobulin G subclasses and serum immunogiobulin A in healthy Norwegian children and adults

IgG subclass concentrations were determined by a capture ELISA antibody assay using monoclonal antibodies to IgG₁, IgG₂, IgG₃, and IgG₄. All the antibodies had been tested for specificity in an IUIS/WHO collaborative study, and this was confirmed by us by testing against purified myeloma proteins representing the 4 subclasses. The sera to be tested were diluted to obtain optimal sensitivity in the lower normal range for each subclass. With these serum dilutions, the lower limit of reading was 1. 2 g/l for IgG₁, 0. 25 g/l for IgG₂, 0.04 g/l for IgG₃ and for IgG₄. Age specific reference limits of the IgG subclass concentrations were determined in serum samples from 138 healthy infants and children under 14 years of age and 66 adults. The reference limits for each age group were determined by calculating the mean ± 2 SD of the logarithms to the values and then taking the antilog of the results. IgA was determined by a turbidimetric method with a reading limit of 0. 1 g/l, and the reference limits were calculated from serum samples from the 138 children under 14 years of age and from 31 healthy adults. The age specific reference limits of the IgG subclasses and IgA are given. Several infants and children had IgG₄ levels below the lower reading limit. To determine lower reference limits of IgG₄ below the age of 7 years was therefore of little clinical significance.     

Comparison of IgG subclasses in foetal serum, maternal serum at delivery and milk in IgA-deficient and control women

Immunoglobulin G subclass concentrations were measured in paired foetal (cord) and maternal serum specimens at delivery from 27 IgA-deficient (serum IgA < 0.01 g/l) and 15 control women. IgA-deficient women had significantly higher serum IgGl and IgG3 concentrations than control women but 2 of the group had concomitant IgG2/IgG4 deficiency and a further 12 had low IgG4 concentrations (serum IgG4 < 0.025 g/l). Foetal serum also had significantly higher IgGl concentrations than control foetal serum but lower IgG2 and IgG4 levels. Concentrations of IgG subclasses and IgM were measured in breast milk collected on the fifth day postpartum from 19 of these IgA-deficient and 18 control women. Between-group differences in IgG subclass levels resembled those in serum. Compared with serum, proportionally less IgG3 was present in milk in both groups although the contribution of IgG3 to total IgG was not less than that of IgG4. Slightly higher IgM was found in milk from the IgA-deficient mothers.     

IgG subclasses in wheezing infants

The wheezing infant is a common but difficult patient to approach diagnostically. The prevalence of IgG subclass antibody deficiency in wheezing infants is still controversial. We studied serum concentration of IgG subclasses in 38 wheezing infants (aged 6–24 months who had not received systemic steroids before investigation) and in 30 healthy age matched control (aged 6–24 months). The prevalence of one or more IgG subclass deficiency was 31.6% in wheezing infants and 26.7% in controls. There was no significant difference in prevalence of IgG subclass deficiency between patients and controls (p>0.05). The mean concentration of IgG subclasses in patients were compared with controls. There was no significant difference in mean serum concentration of IgG1, G2 and G3 subclasses. But there was a trend towards higher concentrations of IgG4 in wheezing infants and this difference for IgG4 was significant (p<0.01). However, IgG subclass deficiency was found in 25% and 36.4% of wheezing infants who had experienced from two to four and five or more wheezing episodes in two years, respectively (p>0.05). These findings suggest that wheezing in infancy is not associated with IgG subclass deficiency and in wheezing infants low IgG subclass levels do not increase the frequency of wheezing.     

Immunoglobulin G subclasses in wheezing infants

Background: The wheezing infant is a common but difficult patient to approach diagnostically. The prevalence of immunoglobulin (Ig) G subclass deficiency in wheezing infants is still controversial. Methods: We studied the serum concentration of IgG subclasses in 38 wheezing infants (aged6–24 months) who had not received systemic steroids before investigation and in 30 healthy age matched controls6–31 months). Results: The prevalence of one or more IgG subclass deficiencies was 3 1.6% in wheezing infants and 26.7% in controls. There was no significant difference in prevalence of IgG subclass deficiency between patients and controls (P > 0.05). The mean concentration of IgG subclasses in patients were compared with controls. There was no significant difference in mean serum concentration of IgG₁, G₂ and G₃ subclasses. However, there a trend towards higher concentrations of IgG₄ in wheezing infants and this difference for IgG₅ was significant (P < 0.01). Immunoglobulin G subclass deficiency was found in 25 and 36.4% of wheezing infants who experienced from two to four and five or more wheezing episodes in 2 years, respectively (P > 0.05). Conclusion: Our findings suggest that wheezing in infancy is not associated with IgG subclass deficiency, and in wheezing infants low IgG subclasses levels do not increase the frequency of wheezing. However, is a relationship between recurrent wheezing and serum IgG₄ subclass concentration.     

Immunoglobulin subclasses and HLA alleles in immunoglobulin A deficiency

Objective : The term “IgA Deficiency (IgAD)” should be reserved for the individuals who do not have detectable disorders known to be associated with low IgA levels. IgG subclass deficiency or a lack of the IgG2 subclass that is specific against polysaccharide antigens, can be seen in many cases.Methods : Forty-five patients (27 males and 18 females; mean age 8.6 years, range 6.3 to 12.8 years) with IgA deficiency who had been admitted to the Department of Pediatric Immunology in Uludag University School of Medicine, Turkey, were included in this study. Serum immunoglobulin (Ig) class and IgG subclass levels, and HLA haplotypes were prospectively determined in patients and healthy controls.Results : Of the 45 patients with IgAD, 1 was found to have a low level of IgG in the serum. Serum Ig levels were also examined in the families of 22 patients. Five patients had low-normal levels of IgM, whilst one had low levels of IgA and IgG. The levels of IgG sublasses were assessed in 23 patients. One patient had a low level of IgG1 ; 2 had low levels of both IgG2 and IgG3, and 11 had low levels of IgG3. IgG subclass concentrations were found to be normal in control groups. HLA alleles were tested in 25 patients. An increased prevelence of HLA-A1, -B8, -B14, -DR1, -DR3, and -DR7 were previously observed in patients with Ig A deficiency. In this study, HLA-A1 allel was found in 3 patients (12 %), HLA-B14 in 3 patients (12%), HLA-DR1 in 10 patients (40 %), HLA-DR7 in 4 patients (16 %) and HLA-DR3 in 1 patient (4 %). HLA-B8 allel was not found in any patient. Twenty-five children with normal IgA levels have chosen as a control group. They had HLA-DR1 (36%), HLA-DR7 (16 %), HLA-B8 (8%), HLA-DR3 (16%). HLA-A1 was not found in any member of our control group.Conclusion : No statistically significant difference in HLA susceptibility alleles was found between patients and healthy controls. Our data suggest that there may be heterogenous HLA distribution patterns in IgA deficiency, or that HLA allel-associated tendency to IgA deficiency may be polygenic.     

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.     

Serum immunoglobulin G subclasses in patients during acute hepatitis A

IgG subclasses were measured in sera of 47 patients with acute hepatitis A during the course of the disease. IgG1 and IgG3 serum levels were found to be elevated, whereas IgG2 and IgG4 subclass concentrations did not differ from that found in healthy control individuals. These findings indicate that, similar to the specific antiviral antibody, the polyclonal increase of serum concentrations of IgG in acute hepatitis A is not equally distributed to all IgG subclasses but is restricted to IgG1 and IgG3.     

反复呼吸道感染患儿IgG亚类及维生素A水平的关联研究

目的：反复呼吸道感染（RRTI）是儿科的常见病之一。目前研究发现其发病与维生素A缺乏,免疫功能异常有关。该研究检测了RRTI患儿IgG 亚类及维生素A水平,并对该类病人维生素A缺乏与IgG亚类缺陷之间的关系进行了初步的探讨。方法：采用ELISA方法检测血清IgG 亚类;采用高效液相色谱分析Miller改良法进行维生素A的测定。结果：RRTI患者血清IgG2,4水平及维生素A水平均低于健康对照组,差异具有显著性（P<0.05）。结论：RRTI患者虽IgG正常,但是可能存在IgG亚类异常。RRTI患者存在维生素A水平低于正常儿童,而且IgG2,4水平的降低可能与维生素A水平有关。［中国当代儿科杂志,2007,9（6）：557-558］     

Serum immunoglobulins, IgG subclasses, isohemagglutinins and complement-3 levels in patients with thalassemia major

Serum IgG, IgM, IgA, IgG subclasses (IgG1, G2, G3, G4), isohemagglutinins and complement-3 concentrations were measured in 23 beta-thalassemic patients suffering from recurrent infections. No significant abnormalities were found in these humoral immunity investigations, both in splenectomized and non-splenectomized patients. On the other hand, iron overload or repeated blood transfusions were not found to down-regulate the humoral immune system of thalassemic patients.     

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.     

Long and short-term effect of prednisolone in hospitalized infants with acute bronchiolitis

OBJECTIVE: To assess long and short-term effect of prednisolone in hospitalized infants with bronchiolitis. METHODOLOGY: A randomized and controlled trial was carried out at the Federal University of Rio Grande, Rio Grande-RS, Brazil. Twenty-eight patients were randomly allocated prednisolone (1 mg/kg/day for 5 days) plus standard care, and 24 patients allocated standard care alone. The primary endpoint was the prevalence of post-bronchiolitis wheezing at 1, 3, 6 and 12 months after hospital discharge. The secondary endpoints were: length of hospital stay, duration of oxygen therapy and time to clinical improvement during the hospitalization. RESULTS: There were no significant differences between the prednisolone and control group in the prevalence of post-bronchioltis wheezing at 1 month (73.1 vs 83.3%, P = 0.5), 3 months (73.1 vs 79.2%, P = 0.7), 6 months (65.4 vs 66.7%, P = 0.9) and 12 months (50.0 vs 58.3%, P = 0.5) after hospital discharge. No reduction was observed in the prednisolone group, compared with the control group, in terms of length of hospital stay (6.0 vs 5.0 days, P = 0.7), duration of oxygen therapy (24.0 vs 24.0 h, P = 0.4) and time to clinical resolution (4.0 vs 4.0 days, P = 0.8). CONCLUSIONS: Prednisolone has no significant effect on reducing the prevalence of post-bronchiolitis wheezing and on improving the acute course of illness in hospitalized infants with bronchiolitis.     

Neutrophil but not eosinophil inflammation is related to the severity of a first acute epidemic bronchiolitis in young infants

Acute bronchiolitis is the main cause of emergency visits and hospitalizations in infants. Recent data suggest that neutrophil- and eosinophil-mediated inflammations were part of bronchiolitis pathophysiology. Apart from the defined risk factors, few was known on the underlying pathophysiology, which might point out the differences observed in the severity of the disease. The aim of this study was to assess whether the clinical severity of acute epidemic bronchiolitis in young infants might be related to a specific underlying inflammatory process. Total and differential cell counts, IL-8, eotaxin, eosinophil cationic protein (ECP) and albumin levels were assessed at the time of admission in bronchial secretions from 37 infants (median age 17 wk) with acute bronchiolitis. Outcome severity variables were: hypoxemia, Silverman score, tachypnea, feeding alteration, and duration of hospitalization. Neutrophils predominated, and eosinophils were present in 54% of the infants. IL-8 levels strongly correlated with ECP and albumin levels. Albumin levels were correlated with ECP and eotaxin levels. IL-8 levels were higher in infants with hypoxemia and inversely related with SaO₂ levels. IL-8 and albumin levels significantly rose with respiratory rate, and Silverman score. IL-8, albumin and ECP levels were significantly higher in infants hospitalized ≥7 days. Furthermore, IL-8 levels were correlated with the duration of hospitalization. Neither cell counts nor eotaxin levels were related to the severity criteria studied. This study suggests that IL-8-associated airway inflammation significantly contributed to the severity of acute epidemic bronchiolitis.     

IgG and IgG subclasses deficiency in children undergoing continuous ambulatory peritoneal dialysis and its provocative factors

BACKGROUND: Low levels of serum IgG or IgG subclasses may be responsible for the defective peritoneal defense and for peritonitis attacks in continuous ambulatory peritoneal dialysis (CAPD) children. Malnutrition, peritoneal loss or frequent peritonitis may lead to IgG or IgG subclasses deficiency. METHODS: Levels of IgG subclasses were determined in 12 children undergoing CAPD treatment. Radial immunodiffusion technique was used for determination. Patients were aged from 6 to 16 years (mean age 12.3 years) and had been on CAPD for 11-26 months (mean duration 19.4 months). We evaluated whether IgG and IgG subclasses deficiency are related to malnutrition, the peritonitis rate and the duration of CAPD using the SPSS program. RESULTS: Serum total IgG levels were found to be low in eight out of 12 patients. Eight patients showed low levels of IgG1, four patients IgG2, one patient IgG3 and three patients IgG4. Total IgG values were found to be positively correlated to malnutrition status, peritonitis rate and duration of CAPD. The IgG2 values were found to be related to the duration of CAPD. The IgG4 values were found to be correlated to the peritonitis rates. CONCLUSIONS: The IgG and IgG subclasses deficiency may develop in children while on CAPD treatment. Periodical determinations of either serum IgG or the subclasses may be useful in the follow-up of these patients.     

Association between pronounced IgA response in RSV bronchiolitis and development of allergic sensitization

Forty-five children who had heen hospitalized with bronchiolitis caused by respiratory syncytial virus (RSV) at a mean age of 4 months, and 90 matched control children, were tested for occurrence of RSV antibodies at one year of age. Of the children who had suffered from bronchiolitis. forty had demonstrable IgG antibodies, whereas the remaining five only had IgA antibodies against RSV. In the control group. 42% were RSV seropositive. The anti-RSV IgA antibody titres tended to be higher in patients with bronchiolitis ihan in controls and a larger proportion of the seropositive children in the former than in the latter group had demonstrable IgG antibodies. These fmdings suggest that RSV infections causing bronchiolitis are more often associated with a strong antibody response than are mild cases of the infection.
Follow-up of the children at 3 years of age showed that allergic sensitization and development of asthma had occurred much more frequently in children with past RSV bronchiolitis than in controls. Children with past RSV bronchiolitis who later developed allergic sensitization had elevated RSV IgA antibody titres at one year of age more frequently than children with past RSV-bronchiolitis. who were not sensitized (p=0.015). No significant differences regarding IgG antibody titres were observed. Since IgA, similarly a. s IgE. antibody formation is strongly Th2 cell dependent, the results are compatible with other fmdings suggesting that RSV has an unusual propensity to activate the Th2 cell system. This may contribute to the pathological picture of bronchiolitis in small children and at the same lime render the infected child predisposed for later development of allergic sensitization. RSV bronchiolitis may thus be an important risk factor for later development of atopic disease although it cannot be excluded that the bronchiolitis simply serves as a marker that predicts later development of atopy.     

病毒性毛细支气管炎的预防和治疗进展

病毒性毛细支气管炎是婴幼儿常见的下呼吸道感染性疾病,是引起婴幼儿喘息的最常见的疾病,与婴幼儿反复喘息和哮喘有密切关系.有关病毒性毛细支气管炎的预防和治疗一直是临床研究的热点.临床对病毒性毛细支气管炎的治疗方法 多样,但疗效多不肯定.文章就近年来对病毒性毛细支气管炎的治疗和预防研究进展作一综述.     

毛细支气管炎患婴肺功能检测及评价

目的观察婴儿毛细支气管炎(毛支)的肺功能动态变化情况以及呼吸道合胞病毒(RSV)感染对其的影响并探讨其临床意义。方法对42例毛支婴儿(其中RSV感染22例)急性期、恢复期及16例正常组婴儿进行肺功能检查。结果毛支急性期呼吸频率(RR)增高、每千克体重潮气量(Vt/kg)、达峰时间比(tPTEF/tE)及达峰容积时间比(vPTEF/vE)均下降,与正常组比较差异有统计学意义;其中RR、tPTEF/tE及vPTEF/vE与恢复期比较差异有统计学意义。而恢复期与正常组比较各项指标差异均无统计学意义。在急性期RSV感染毛支患儿tPTEF/tE、vPTEF/vE下降更明显,与非RSV感染患儿比较差异有统计学意义;在恢复期RSV感染患儿与非RSV感染患儿比较,各项指标差异均无统计学意义。结论毛支急性期,肺功能呈现小气道阻力增高、阻塞性通气障碍改变,恢复期小气道功能好转,说明小气道功能异常能在较短时间内恢复。同时在急性期RSV感染比非RSV感染引起更强的下呼吸道阻塞的肺功能表现。婴儿肺功能检查是判断病情、评估疗效、推断预后的实用和可靠的方法。     

Serum IgG subclass concentrations in healthy subjects at different age: Age normal percentile charts

IgG subclass levels were determined in 448 normal children from 6 months to 18 years of age and in 141 healthy adults by radial immunodiffusion using monoclonal antibodies. Age-normal percentile values were calculated for each year of age up to 18 years for IgG1, IgG2, IgG3 and in adults for all four subclasses. The broad spread of IgG4 values in children did not permit calculation of reference values.