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］     

IgG2 deficiency in children with human immunodeficiency virus infection

Infection with the human immunodeficiency virus (HIV) induces a polyclonal B-cell activation. Despite elevated serum immunoglobulin levels, a significant deterioration of the antigen specific humoral immune response exists in most cases. We studied the influence of HIV infection on the serum levels of IgG subclasses in children. We investigated 76 children (aged 15 months to 18 years) with HIV-1-infection. Most children (88%) showed elevated serum immunoglobulin levels. IgA (87%) and IgM (74%) were more often above normal levels for age than IgG (60%). IgG subclass serum levels were significantly altered. The increase in total IgG was mainly due to a marked augmentation of the IgG1 fraction. In most cases IgG3 was simultaneously elevated. Ten children (13%) had very low IgG4 levels (<0.03 g/l). Out of 61 patients older than 2 years 8 (13%) had a profound IgG2 deficiency with normal or elevated total IgG. Four of them also had low IgG4 levels (<0.03 g/l). A correlation between IgG2 deficiency and HIV infection according to the Centres for Disease Control classification for acquired immunodeficiency syndrome could not be demonstrated (three patients with symptomatic and five with asymptomatic infection).     

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.     

Increased IgG2 and IgG3 concentration is associated with advanced Pseudomonas aeruginosa infection and poor pulmonary function in cystic fibrosis

The concentrations of IgG subclass immunoglobulins were determined by radial immunodiffusion in serum from 126 patients with cystic fibrosis (CF). The results were compared to values from age-matched healthy children and adults and correlated to patients age, duration of chronic Pseudomonas aeruginosa infection and lung function parameters. Fifty-two percent of the patients had an elevated concentration of at least one of the IgG subclasses; IgG1 28%, IgG2 16%, IgG3 18% and IgG4 48%. There was significant correlation between elevated serum levels of IgG2, and to a lesser extent IgG3, with decreased lung function (for FEV1; p = 0.0001, and p = 0.001 respectively) and high levels of antipseudomonas precipitins (p = 0.008, and p = 0.002). A similar correlation was not found for IgG1 and IgG4. IgG subclasses vary in their ability to promote phagocytosis and to activate complement and it is possible that individual differences in the IgG subclass pattern could explain the variable course of this disease.     

Increased IgG2 and IgG3 Concentration Is Associated with Advanced Pseudomonas Aeruginosa Infection and Poor Pulmonary Function in Cystic Fibrosis

ABSTRACT. The concentrations of IgG subclass immunoglobulins were determined by radial immunodiffusion in serum from 126 patients with cystic fibrosis (CF). The results were compared to values from age-matched healthy children and adults and correlated to patients age, duration of chronic Pseudomonas aeruginosa infection and lung function parameters. Fifty-two percent of the patients had an elevated concentration of at least one of the IgG subclasses; IgG1 28%, IgG2 16%, IgG3 18% and IgG4 48%. There was significant correlation between elevated serum levels of IgG2, and to a lesser extent IgG3, with decreased lung function (for FEV₁; p =0.0001, and p =0.001 respectively) and high levels of antipseudomonas precipitins ( p =0.008, and p =0.002). A similar correlation was not found for IgG1 and IgG4. IgG subclasses vary in their ability to promote phagocytosis and to activate complement and it is possible that individual differences in the IgG subclass pattern could explain the variable course of this disease.     

IgG subclasses in nonallergic children with chronic chest symptoms

Immunoglobulin and IgG subclass measurements were made on sera from 37 children thought to have asthma whose chronic chest symptoms were unexplained by allergy. There was a higher proportion of low or low-normal levels of IgG subclasses 1, 2, and 4 in these children than in normal children. Those who had low serum IgG values on initial measurement had a higher proportion of low or low-normal levels of IgG1, IgG2, and IgG4; those who had normal IgG values had a higher proportion of low or low-normal levels of IgG2 and IgG4. Thus a normal serum concentration of IgG did not exclude the possibility of an abnormal level of IgG2 or IgG4. Our experience suggests that abnormal levels of IgG subclasses might play an etiologic role in the chronic chest symptoms in some of these children.     

Serum immunoglobulin G subclasses in children infected with human immunodeficiency virus type 1

We studied serum concentrations of IgG subclasses in 47 human immunodeficiency virus 1-infected (17 asymptomatic and 30 symptomatic) children. Thirty-nine of 47 (83%) had an abnormality of at least 1 subclass. Sixteen had only elevated IgG1, 6 had only elevated IgG3 and 12 had elevated IgG1 and IgG3 concentrations. IgG2, IgG4 and combined IgG2-IgG4 deficiency was found in 3, 4 and 4 patients, respectively. IgG2 concentrations did not differ between patients with (n = 23) or without (n = 24) bacterial infections. Additionally the number of bacterial infections was similar between the patients with normal or low IgG2 and/or low IgG4. These data indicate that IgG subclass abnormalities are found in most children with human immunodeficiency virus 1 infection, but quantitative deficiencies of specific subclasses do not appear to explain the high frequency of bacterial infections occurring in these patients.     

Effect of Anti-Epileptic Drugs on Serum Level of IgG Subclasses

Objective

There are some controversial studies on effects of anti-epileptic drugs (AEDs) on serum IgG subclasses; however, the role of these medications is still unclear. The aim of this study was evaluation the effects of anti-epileptic drugs on serum concentration of IgG and its subclasses

Methods

Serum IgG and IgG subclasses of 61 newly diagnosed epileptic patients were measured at the beginning of monotherapy with carbamazepine, sodium valproate, and phenobarbital, and 6 months later. Measurement of IgG and its subclasses was performed using nephlometry and ELISA techniques, respectively.

Findings

Reduction of at least one IgG subclass was found in 6 patients 6 months after treatment with AEDs. Among 27 patients receiving carbamazepine, decrease in at least one serum IgG subclass level was found in 5 patients. Among 20 patients using sodium valproate, only one patient showed decrease in IgG2 subclass. None of the 14 patients using phenobarbital revealed significant decrease in IgG subclasses. No infection was seen in the patients with reduction of subclasses.

Conclusion

Although in our study, children with selective IgG subclass deficiency were asymptomatic, assessment of serum immunoglobulin levels could be recommended at starting the administration of AEDs and in serial intervals afterward in epileptic patients.     

Abnormal maxillary sinus radiographs in children: do they represent bacterial infection?

Thirty-three children with chronic tonsillitis and/or adenoid enlargement and without previous diagnosis of sinusitis were studied regarding the bacterial flora of their maxillary sinuses. Puncture of maxillary sinus was performed at surgery (adenoidectomy and/or tonsillectomy) and aspirates were cultured. Streptococcus pneumoniae was isolated from 8 of 12 (66.7%) patients whose x-rays showed completely opacified maxillary sinus. Streptococcus viridans, Streptococcus faecalis, and Staphylococcus epidermidis were recovered from 6 (28.6%) of the 21 patients with normal maxillary sinus radiographs. Bacterial titers were greater than 10(4) colonies/mL in all but one of the positive cultures. No anaerobic bacteria were isolated. History of bronchial asthma, presence of nasal purulent secretion, elevated blood eosinophils, and elevated serum IgE were found more frequently in children with complete opacification of maxillary sinus. Serum levels of IgG2 were low in 29% of the children, but no correlation was found between low IgG2 levels and positive cultures from maxillary sinus aspirates. We concluded that children with complete radiologic opacification of maxillary sinus had bacterial infection in almost 70% of the cases with symptoms that did not prompt their physicians to consider the diagnosis of sinusitis.     

Immunological evaluation of allergic respiratory children with recurrent sinusitis

The objective of this study was to evaluate humoral immunity of allergic respiratory children with chronic/recurrent sinusitis. Twenty-seven allergic respiratory (persistent mild/moderate asthma and persistent allergic rhinitis) children (7-15-year old) with chronic or recurrent sinusitis were evaluated. Patients had symptoms and abnormal computer tomography scan even after two adequate treatments (long-lasting antibiotics, decongestants, and short-term oral corticosteroids). clinical examination, sweat test, total blood cell count, measurement of serum levels of: total and specific IgE, immunoglobulins (G, M, A), IgG subclasses, antibodies to Haemophilus influenza type b (IgG anti-Ps Hib) and pneumococcal serotypes (IgG anti-Ps 1, 3, 5, 6B, 9V, and 14) before and after active immunization (Act-Hib and Pneumo23, Aventis Pasteur SA, Lyon, France), Rubella neutralizing antibody titers and human immunodeficiency virus antibodies. Specific IgE to inhalant allergens higher than class III were observed in 24/27 patients. One patient had IgA plus IgG2 deficiency and other an IgG3 deficiency. Eight and 12 of 27 patients had IgG2 and IgG3 serum levels below 2.5th percentile, respectively. Immunological responses to protein and polysaccharide antigens were normal in all patients. Although our patients have been appropriately treated of their allergic diseases, they persisted with chronic/recurrent sinusitis and 60% of them had a documented osteomeatal complex blockade. In spite of the diagnosis of IgA plus IgG2 deficiency and an isolated IgG3 deficiency, in all patients an adequate response to Ps antigens was observed. Primary and/or secondary humoral immunodeficiency seems not to be the main cause of chronic/recurrent sinusitis in patients with respiratory allergic disease.     

IgG Subclass Imbalance in Children with Acute Lymphoblastic Leukemia Receiving Maintenance Chemotherapy

Serum levels of IgG subclasses were measured in 18 children with acute lymphoblastic leukemia (ALL) receiving maintenance chemotherapy and in 36 age-matched controls in order to attempt to analyse the effects of chemotherapy. The IgG subclasses were measured by enzyme linked immunosorbent assay. Serum IgG₁, IgG₂ and IgG₄ levels in the patients were significantly (p<0.01, p<0.005, p<0.005) lower than in the controls, but serum IgG₃ levels in patients were as high as in controls. Suppression on IgG₂ and IgG₄ were more profound than IgG₁. In six children, the levels of the IgG subclasses were measured at diagnosis, during maintenance chemotherapy and one year after cessation of chemotherapy. The levels of the four IgG subclasses at diagnosis and after cessation of chemotherapy were as high as those in control children except for the IgG₄ levels in the postchemotherapy group. IgG₂ and IgG₄ may be more susceptible to suppression by chemotherapy than IgG₁ and IgG₃ may not be suppressed by chemotherapy.     

Evaluation of serum levels of IgG subclasses and anti-ribosyl-ribitolphosphate IgG and IgG2 in children with Haemophilus influenzae b meningitis.

In 40 children with Haemophilus influenzae b (Hib) meningitis, we determined serum levels (mg/dl) of IgG subclasses using the radial immunodiffusion method; 67.8 per cent of these children were less than 24 months old. In 14 children of the sample we measured serum IgG and IgG2 anti-ribosyl-ribitolphosphate (anti-PRP) (by enzyme-linked immunosorbent assay, ELISA) in the acute and convalescent phases of the disease. Lower IgG2 levels than those of the control group were obtained in all age ranges: 3-12 months, 1-2 years (p < 0.01), and 2-5 years (p < 0.001). IgG4 was also present in lower levels in patients of all age ranges (p < 0.05, p < 0.001, and p < 0.01 respectively). Serum levels of IgG anti-PRP and IgG2 anti-PRP measured were very low in the acute phase of the disease in all age ranges and there was no notable increase in levels during the convalescent phase of the disease. This result indicates that children less than 24 months old do not produce sufficient levels of IgG and IgG2 anti-PRP even after Hib meningitis.     

Severe chronic active Epstein-Barr virus infection syndrome and adenovirus type-2 infection

Four patients from 4 to 24 years of age (3 males, 1 female) with generalized lymphadenopathy, hepatosplenomegaly, and intermittent fever associated with chronic active Epstein-Barr virus (EBV) infection were investigated. Laboratory data showed polyclonal gammopathy and a tendency for bone marrow suppression. Noteworthy were the extremely elevated immunoglobulin G (IgG) antibody titers to Epstein-Barr viral capsid antigen (VCA) (range, 10,240-81,920) and early antigen (EA) (range, 1,280-40,960). All patients had IgA antibodies to VCA and EA. Subtle, heterogeneous immune functional defects were observed in all four patients. Another unusual feature was our inability to establish spontaneous or B95-8 EBV-immortalized lymphoblastoid cell lines (LCLs) due to a marked cytopathic effect (CPE). Thus, we investigated for other viruses. Both IgG and IgM antibodies to adenovirus type-2 (Ad-2) were positive by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence (IF) test, suggesting recent or activated Ad-2 infection had occurred. Dual active EBV and Ad-2 infections were likely etiologic in this severe chronic active EBV infection syndrome.     

The IgG subclass level in children and adolescents with malignant diseases]

Children with malignant disease have an increased risk for bacterial infections. We investigated a possible correlation between septic episodes and decreased IgG subclass levels in 63 patients. At diagnosis 13 of 50 children showed decreased IgG subclass levels: 10x IgG4, 2x IgG1, and 1x IgG3 + IgG4 were reduced. Bone marrow infiltration by tumor cells did not increase the frequency of subclass reductions (4/25 with, 9/25 without bone marrow infiltration). The time course of subclass levels was followed during 37 febrile episodes (mainly fever of unknown origin, septicemia, pneumonia) of 23 children under cytostatic therapy. 6 patients showed transient low IgG subclasses: 2x IgG4, 1x IgG1, 1x IgG3, 1x IgG2 + IgG4, and 1x IgG1 + IgG3 + IgG4. Children with decreased IgG subclass levels appeared to occur more independently of leucopenia. In general, febrile episodes in children with subclass decreases did not last a longer period and did not occur more frequently than in children without IgG subclass deficiencies. In conclusion, the determination of IgG subclasses in cancer children at diagnosis or during chemotherapy did not add substantial information of prognostic or therapeutic relevance.     

Placental transfer of IgG subclasses in a Japanese population

BACKGROUND: Maternal immunoglobulin G (IgG), transferred across the placenta to the fetus during intrauterine life, is an important component of the neonatal immunological defence mechanisms against infection. There is controversy with respect to differences in placental transfer of the different IgG subclasses, and no definite data are available on a Japanese population. Therefore, we investigated placental transfer of IgG subclasses in a Japanese population. METHODS: A total of 228 matched pairs of cord and maternal serum samples (20-42 weeks gestation) were assayed for each IgG subclass by an enzyme-linked immunosorbent assay. RESULTS: The mean values and hierarchy of cord/maternal concentration ratios of IgG subclasses at 40 weeks gestation were as follows: IgG1(1.47) > IgG3(1.17) = IgG4(1.15) > IgG2(0.80). The cord/maternal concentration ratios of all IgG subclasses were positively correlated to gestational age. The mean ratios for IgG1 and IgG4 nearly reached a plateau at 39 and 37 weeks gestation, respectively, while those for IgG2 and IgG3 increased until 41 weeks gestation. The ratios of all IgG subclasses for full-term deliveries were reciprocally correlated to the respective maternal IgG subclass serum levels. CONCLUSIONS: The results suggest that although all four IgG subclasses are actively transferred across the placenta, the efficiency of their transfer ranks in the order IgG1 > IgG3 = IgG4 > IgG2. The different results as to placental transfer of IgG subclasses in the literature might be due, at least in part, to different maternal IgG subclass serum levels in the populations studied.     

Formation of specific IgG antibodies in l-asparaginase treatment. Distribution of IgG subclasses

During l-Asparaginase (l-Asp) treatment the development of specific antibodies of IgG isotype is frequently observed. In most instances elevated IgG antibodies to l-Asp activate the complement system and induce allergic reactions following l-Asp infusion. However, in some cases no adverse reactions and no activation of complement are noticed, despite the presence of elevated anti-l-Asp levels. We studied the development of specific IgG antibodies to l-Asp in different subclasses in 12 children who had produced high levels of specific IgG. Results showed that all patients had elevated levels of IgG1. In 5 cases we were able to demonstrate the development of specific IgG3 antibodies and in 1 case of IgG4 antibody. Patients with high levels of IgG3 (above 100 AU) had the highest risk for subsequent anaphylaxis. Thus, subclass-specific determination of antibodies to l-Asparaginase might improve the estimation of the risk of anaphylaxis prior to 1-Asp infusions.     

Immunoglobulin G subclass deficiency and predisposition to infection in Down's syndrome

Serum immunoglobulins and IgG subclasses were measured in 26 children with Down's syndrome using an enzyme-linked immunosorbent assay and monoclonal antibodies. Eighteen (69%) of the children had increased susceptibility to infection. None of the children had deficiencies of total IgG and IgM, and only one had an IgA deficiency. IgG4 deficiency was diagnosed in 14 (54%) children. One child had a deficiency of IgG2. There were no children with deficiencies of either IgG1 or IgG3. There was a significant correlation between IgG subclass deficiency and predisposition to infection (P less than 0.05). Ninety percent of the patients with severe infections had low IgG4 whereas only 25% of those with no infections had low concentrations of IgG4. These results suggest that it is important to screen patients with Down's syndrome who have frequent systemic or respiratory infections for IgG subclass deficiencies because this may not be apparent from the assay of total IgG.     

Cow's milk and ovalbumin-specific IgG and IgA in children with eczema: low β-lactoglobulin-specific IgG4 levels are associated with cow's milk allergy

To cite this article: Savilahti EM, Viljanen M, Kuitunen M, Savilahti E. Cow's milk and ovalbumin-specific IgG and IgA in children with eczema: low β-lactoglobulin-specific IgG4 levels are associated with cow's milk allergy. Pediatric Allergy Immunology 2012: 23: 590-596. ABSTRACT: Tolerance to allergens may partly depend on allergen-specific IgG and IgG subclasses and IgA antibodies. We investigated whether specific IgG and IgG subclasses and IgA antibodies to β-lactoglobulin, α-casein, and ovalbumin differed between infants who had verified cow's milk allergy (CMA) and infants with cow's milk (CM)-associated eczema, but negative CM oral challenge. The study population comprised 95 infants with clinical eczema that was by history associated with the consumption of CM. After an elimination period, a double-blind, placebo-controlled (DBPC) CM oral challenge confirmed CMA in 45 infants. Skin prick tests (SPT) were performed with CM and hen's egg. Serum levels of IgE antibodies to CM and hen's egg were measured with UniCAP (Phadia, Uppsala, Sweden), and levels of IgA, IgG, IgG1, and IgG4 antibodies to β-lactoglobulin, α-casein, and ovalbumin were measured with enzyme-linked immunosorbent assay. We observed that infants with CMA had lower IgG4 levels to β-lactoglobulin than infants with negative DBPC CM challenge (p?=?0.004). Positive CM SPT was associated with lower IgG4 levels to α-casein (p?=?0.04). The relation of CM IgE to β-lactoglobulin and α-casein IgG4 was higher in CMA than in infants with negative challenge (p?相似文献   

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.     

AUTOANTIBODIES TO TAMM-HORSFALL GLYCOPROTEIN IN CHILDREN WITH RENAL DAMAGE ASSOCIATED WITH URINARY TRACT INFECTIONS

Abstract. Fasth, A., Bjure, J., Hellström, M., Jacobsson, B. and Jodal, U. (Departments of Pediatrics, Clinical Immunology, Pediatric Clinical Physiology and Pediatric Radiology). Autoantibodies to Tamm-Horsfall glycoprotein in children with renal damage associated with urinary tract infections. Acta Paediatr Scand, 69: 709, 1980.—Autoantibodies to the Tamm-Horsfall (TH) protein were analyzed in sera from 116 patients with pyelonephritis. The increases in antibody levels were limited in 23 patients with radiological detected renal damage during 31 attacks of acute pyelonephritis. 8 children with abnormally low total and/or unilateral ⁵¹Cr EDTA clearance had significantly lower IgG antibody levels to TH protein, than 14 children with normal clearance rate. All 61 children with renal damage had significantly low IgG, IgA and IgM antibody levels to TH protein 6 months after last infection as compared to the reference group. For IgG antibodies, the mean was well below –2 S.D. 12 children with increased serum creatinine had significantly lower IgG antibody levels than those with normal creatinine. No correlation was found between antibody levels and vesico-ureteric reflux. In contrast, 55 children with no renal damage still had significantly increased IgG and IgA antibody levels to TH protein 6 months after the infection. The mechanism for the low antibody levels was discussed and it was concluded that patients with urinary tract infection and low IgG antibody levels to TH protein were at risk for renal damage and should be radiologically examined.