Epidemiology of allergic reactions to hymenoptera stings in Irish school children

Jennings A, Duggan E, Perry IJ, Hourihane JO’B. Epidemiology of allergic reactions to hymenoptera stings in Irish school children.
Pediatr Allergy Immunol 2010: 21: 1166–1170.
© 2010 John Wiley & Sons A/S The aim of this was to study generate the first epidemiological data regarding the prevalence of hymenoptera allergy among school children in Ireland. Questionnaires, including six sting‐specific questions ( 1 ), were distributed to the parents of primary school children aged 6–8 and 11–13, divided equally between rural and urban backgrounds. From 110 schools, 4112 questionnaires were returned. A total of 1544 (37.5%) children had been stung in their lifetime. Among the total, 5.8% of children stung experienced a large local reaction, 3.4% had a mild (cutaneous) systemic reaction (MSR) and 0.8% experienced a moderate/severe systemic reaction (SSR); these figures respectively represent 2.2%, 1.3% and 0.2% of the total study group. On logistic regression analysis, older children and rural children were at a higher risk of being stung (OR 1.7; 95% CI 1.4–2.; OR 1.6; 95% CI 1.4–1.8 respectively). Rural dwellers and asthma sufferers were more likely to experience an SSR (OR 4.3; 95% CI 1.4–13.5 and OR 2.8; 95% CI 1.8–4.3, respectively). Hymenoptera stings are more common in rural than urban dwelling Irish children. Asthma imparted a greater risk of SSR in this study population. Severe reactions are unusual overall, occurring in <1% of those stung, a lower prevalence than in Israeli teenagers but in keeping with other European reports relating to young children.     

The prognostic significance of specific IgG antibodies in insect sting allergy

Specific IgG antibodies against bee venom and bee venom components were studied in the serum of 40 bee-sting allergic patients, 60 bee keepers, and 31 control subjects. The highest titres were observed in successfully hypothesized patients and in bee keepers. Subclass-typing in bee-sting allergic patients showed the highest antibody levels in subclass IgG 2, followed by IgG 3, IgG 4 and IgG 1. During hyposensitization, a rise in specific IgG antibodies in all subclasses and against bee venom and all its components was found. The allergic reaction to bee stings disappeared with the rise of specific IgG antibodies, as demonstrated by a bee-sting challenge. After 6 months of hyposensitization therapy, the specific IgG antibodies remained above, and the specific IgE antibodies fell below, the pretreatment levels.     

Concentrations of antibodies in paired maternal and infant sera: relationship to IgG subclass

Previous studies comparing IgG subclass concentrations in cord and maternal sera have indicated that IgG1 is transported across the placenta to a greater extent than is IgG2. The purpose of our study was to examine the relationship between the transport of IgG1 and IgG2 and the transport of specific antibodies that are relatively restricted to a particular subclass, either IgG1 or IgG2. The concentrations of total serum IgG1 and IgG2 and those of IgG-anti-tetanus toxoid (TT) and anti-group A streptococcal carbohydrate (GAC) were measured in 30 paired maternal and cord sera. Previous studies have shown that anti-TT in adults is predominantly IgG1, whereas anti-GAC is predominantly IgG2. The mean cord/maternal concentration ratios of IgG1 and anti-TT were similar (1.77 +/- 0.56 and 1.93 +/- 0.67, respectively), but differed significantly (P = 0.0001) from those of IgG2 and anti-GAC (0.99 +/- 0.39 and 1.01 +/- 0.45, respectively). We confirmed the difference in cord/maternal concentration ratios of IgG1 and IgG2 antibodies by measuring IgG1 and IgG2 antibodies specific for Haemophilus influenzae type b capsular polysaccharide; the mean cord/maternal concentration ratio of IgG1-anti-Hib PS was significantly higher than that of IgG2-anti-Hib PS (2.23 +/- 0.83 compared with 0.94 +/- 0.49, P = 0.01). These results indicate that placental transport of IgG antibodies is related to their subclass composition.     

The role of neutralizing antibodies in protection of American Indian infants against respiratory syncytial virus disease

BACKGROUND: Navajo and White Mountain Apache infants have respiratory syncytial virus (RSV) hospitalization rates 2-5 times that of the general U.S. infant population. To evaluate whether these high rates can be attributable to low concentrations of maternally derived RSV neutralizing antibodies, we conducted a case-control study. METHODS: Study subjects enrolled in a prospective, hospital-based surveillance study of RSV disease and a group randomized clinical trial of a 7-valent pneumococcal conjugate vaccine. Cord blood specimens were assayed for neutralizing RSV antibody titers. Infants hospitalized with a respiratory illness had a nasal aspirate obtained to determine whether RSV was present. Infants with an RSV respiratory hospitalization were matched by date of birth and geographic location to infants who did not have an RSV hospitalization before 6 months of age. RESULTS: For every 1 log2 increase in titer of cord blood RSV neutralizing antibodies there was a 30% reduced risk of hospitalization with RSV (OR = 0.69, P = 0.003). However, among infants hospitalized with RSV, there was no association between cord blood RSV neutralizing antibody and the severity of the RSV illness. CONCLUSIONS: These findings indicate that American Indian infants with high concentrations of maternally derived RSV neutralizing antibodies are protected from RSV hospitalization before 6 months of age. However, these antibodies do not modify the severity of illness once disease has occurred. The basis for elevated rates of RSV disease among American Indian infants cannot be attributed to a failure of maternal RSV neutralizing antibodies to confer protection.     

The detection of IgG antibodies to silicone

Following a recent report of an ELISA test for the detection of antibodies to silicone, we attempted to use the same assay in four patients with known exposure to silicone. These patients all gave similar positive results as did a number of control sera with no known silicone exposure. We conclude that this assay does not measure serum levels of antibodies to silicone.     

IgG subclass deficiency in childhood. Changes in the antigen specific immune response and significance of low IgG4 level

The definition of IgG subclass deficiency and the correlations between low IgG subclass serum concentrations and high incidence of infections in certain patients are still obscure. Therefore 260 children from 6 months to 18 years with severe recurrent infections or a known immunodeficiency were screened for IgG subclass deficiency. Nine patients with severe IgG2 deficiency (Ig2 less than 0.3 g/l) and 35 patients with non-detectable IgG4 in immunoprecipitation were detected. One of these patients had a concomitant IgA deficiency, eight revealed an additional IgA and IgG2 deficiency, two an IgA, IgG2, and IgG3 deficiency, eighteen an IgG2 deficiency and one patient an IgG2 and IgG3 deficiency. The proportion of patients with non-detectable IgG4 in immunoprecipitation was 13.5% and thus in the same order of magnitude as described in the literature for healthy people. Our data show that there is no relation between low IgG4 serum levels and the increased occurrence of severe infections. In all patients investigated with non-detectable IgG4 in immunoprecipitation the gene for the heavy chain gene constant domain C gamma 4 could be detected by Southern blotting. Using a sensitive ELISA method IgG4 could be directly demonstrated in all patients at a serum level of 0.5-29 micrograms/ml. Specific IgG4 antibodies against protein antigens could not be detected in IgG4-deficient patients. Nevertheless total IgG antibodies against diphtheria and tetanus toxoid reached protecting titers. Patients with IgG2 deficiency showed an impaired immune response against polysaccharides from pneumococci and haemophilus influenzae type b.     

Increased rate and greater severity of allergic reactions to insect sting among schoolchildren with atopic diseases

The question of whether atopic diseases are a risk factor for allergic reactions to insect sting is still unresolved. The aim of this study was to evaluate the association between atopic diseases (asthma, allergic rhinitis, atopic eczema) and allergic reactions to insect stings among schoolchildren in Israel. A self‐report questionnaire of the International Study of Asthma and Allergies in Childhood was administered to a national sample of 13–14‐yr‐old schoolchildren. Questions regarding reactions to insect stings were added. A total of 10,021 questionnaires were available for analysis. Among the children who reported insect stings (56.3%), the prevalence of current asthma was 6.0%, of allergic rhinitis, 10.5%, and of atopic eczema, 8.7%, with no significant differences from the whole study population. Among children with any of the atopic diseases, 36.9% reported an allergic reaction to insect sting compared to 24.8% of the non‐atopic children (p < 0.0001). On multivariate analysis, asthma, allergic rhinitis, and atopic eczema were found to be significant risk factors for allergic reactions of any severity. Children in the atopic group had a significantly higher rate of severe allergic reactions than the non‐atopic children, and relatively higher rates of milder ones (p < 0.0001). Asthmatic patients with severe allergic reactions had more parameters of severe asthma than asthmatic patients with mild or no reactions. In conclusions, allergic diseases are associated with a higher rate and greater severity of allergic reactions to insect sting in children. The severity of the allergic reaction is related to the severity of the asthma symptoms.     

Human IgG antibodies to carbohydrate and protein antigens in mouse protection tests with group B streptococci

The protective effect of four commercial human gammaglobulin batches (I-IV) in mice was studied using six different strains of group B streptococci (GBS): types Ia; Ib; II, R-protein negative (R-); II, R+; III, R-; and III, R+. Each mouse received 1.0 ml gammaglobulin and 0.5 ml bacteria, 10(6)-10(8) colony forming units (CFU). There was a close correlation between antibody levels measured by the use of radiolabeled protein A and the mouse-protective effect of the gamma-globulins. The mouse-protection tests demonstrated that batch I protected against GBS types Ia and III, R- at low concentration (65 mg/kg mouse weight), against type Ib at medium (260 mg/kg) and against type III, R+ at high concentration. Batch IV protected against types Ia and Ib, although the doses were four times higher than those in batch I, but did not protect against type III, R+. There was no mouse protection by any of the batches against type II. Antibody levels against Ibc and R, protein antigens, were substantially lower in batch IV. Because the results of these mouse-protection studies indicate the importance of such antibodies against protein antigens, batches I-III might be more useful for therapy of neonatal GBS-septicemia.     

Serotype-specific serum IgG antibodies to lipopolysaccharides of Pseudomonas aeruginosa in cystic fibrosis: correlation to disease, subclass distribution, and experimental protective capacity

Various studies have demonstrated pronounced systemic IgG response to Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF). However, antibody response to serotype-specific lipopolysaccharides (LPS) has never been studied. ELISA for detection of IgG antibodies to LPS of nine PA-serotypes and to toxin A were performed with serum of 78 CF patients. Anti-LPS profiles of antibodies were confirmed by SDS-PAGE and immunoblotting techniques. The most frequent PA-serotypes found were immunotypes (IT) IT-1 and IT-2, and Habs-3 and Habs-4. Ten patients without PA colonization showed no detectable antibody titers. In patients with chronic PA colonization (n = 46), these antibody titers were significantly (p less than 0.005) higher than in patients with intermittent PA colonization (n = 22). Mean serum antibody titers to LPS of PA IT-1, IT-2, Habs-3, and Habs-4 correlated with duration of PA colonization and with disease severity. Subclass analysis of anti-LPS antibodies revealed elevated levels for all four IgG subclasses and for IgA1. The IgG antibodies to LPS of PA proved to be protective in a murine burn wound sepsis model. We conclude that anti-LPS antibodies to specific PA serotypes in serum may be a sensitive measure of severity and prognosis of CF. Patients with CF show adequate functional immune response to LPS of PA, and it is possible that vaccination against PA before colonization could induce protective immunity.     

Development of IgE and IgG antibodies to food and inhalant allergens in children at risk of allergic disease.

In a prospective study of 92 children with at least one atopic parent, the development of the specific antibody responses to food and inhalant allergens during the first 5 years of life were assessed. By the radioallergosorbent test egg specific IgE antibody occurred in about 30% of the children with the mean peak concentration at 12 months. By the second year the prevalence of this antibody had increased whereas the mean concentration had decreased. Milk specific IgE antibody could not be shown in any subject, including four whose skin tests yielded positive results. Food specific IgG antibody was noted by antigen binding radioimmunoassays at 3 months in most children. These responses had peaked and began to fall by the fifth year. In contrast few children had detectable IgE or IgG antibody to inhalant allergens before the first 2 years of life. Both the concentration and prevalence of specific antibody, however, increased from the second to the fifth year and was greater in children whose skin tests yielded positive results. Breast feeding was associated with an increase in the prevalence of positive results from skin tests but was not associated with detectable IgE antibody to both food proteins, a lower concentration of IgG antibody to cows'' milk, and was not associated with protection against the development of disease. A high level of exposure to dust mite was associated with an increased prevalence of positive results from skin tests to dust mite and appreciably higher antibody concentration. This study indicates differences in the humoral responses to food and inhalant allergens. Environmental factors appear to influence the development of these responses.     

Modulation by human milk of IgG subclass response to hepatitis B vaccine in infants

The influence of breast and formula feeding on specific anti-hepatitis B surface antigen (HBsAg) IgG subclass production and distribution has been investigated in 40 healthy infants, born to HBsAg-positive mothers and vaccinated against hepatitis B virus (HBV). Twenty children were bottle fed and 20 were breast fed. Specific subclasses were detected at the 4th and 12th months using an enzyme-linked immunosorbent assay with monoclonal antibodies. A defect in total IgG and IgG subclasses was previously excluded. Significant differences were observed both at the 4th and 12th months for IgG1 and IgG2. Breast-fed infants had significantly higher levels of specific IgG2 (about three times higher), while IgG1 levels were significantly higher in formula-fed infants. Anti-HBsAg IgG4 levels were always higher in bottle-fed infants, but a statistical significance was never present. No difference was found in specific IgG3 levels. This study reports the evidence that breast feeding influences specific IgG subclass synthesis against a viral antigen and suggests an immunologic modulation of the response to vaccines dependent not only on age but also on factors present in human milk.     

长期特异性免疫治疗对螨过敏儿童血清IgG4的影响

目的探讨长期特异性免疫治疗对螨过敏儿童血清IgG4的影响。方法对60例过敏性哮喘和(或)过敏性鼻炎的患儿,予屋尘螨特异性过敏原免疫治疗,在治疗前、治疗16周、治疗1年和治疗3年时分别进行血清IgG4检测。结果随着治疗的进行,螨特异性IgG4显著增高(F=83.91,P<0.001),各时间段差异均有统计学意义(P均<0.01),并且以治疗剂量递增过程患儿血中螨特异性IgG4含量增长最快,在三年治疗结束时血清IgG4值达到最高。结论螨特异性过敏原免疫治疗对患儿体内免疫状态有明显的调节作用,有利于改善螨过敏患儿的症状和体征。     

Correlation of allergen‐specific IgG subclass antibodies and T lymphocyte cytokine responses in children with multiple food allergies

Scott‐Taylor TH, Hourihane J, Strobel S. Correlation of allergen‐specific IgG subclass antibodies and T lymphocyte cytokine responses in children with multiple food allergies.
Pediatr Allergy Immunol 2010: 21: 935–944.
© 2010 John Wiley & Sons A/S Cytokines can affect the quantity and class of allergen‐specific immunoglobulins through the T cell polarization that accompanies atopy. Antigen‐specific IgG subclasses and IgE antibodies were compared with intracellular T cell cytokine changes to sensitizing antigens in 23 children with multiple food allergies and 20 healthy controls. Allergic children showed higher levels of total and food‐specific IgE, IgG1 and IgG4 to peanut, milk and egg than non‐atopic children or adults, coinciding with a TH2 cytokine response to sensitizing antigens. IgG1 and IgG4 antibodies specific to milk and egg and peanut protein were elevated relative to age‐matched healthy children (p ≤ 0.05) and, in milk‐ and egg‐sensitized children, correlated with cytokine responses (p < 0.05). Peanut‐sensitized children additionally had elevated levels of IgG2 and IgG3 also which correlated inversely (p < 0.003 and p < 0.04, respectively) with IFNγ production. Elevated allergen‐specific IgG subclass antibodies in sensitized children correlated with total IgE levels (p ≤ 0.05) in all three food allergen groups. The ratio of specific IgG1 to IgG4 was highest in those with high IgE, inverted with resolution of allergy, and correlated with total IgE levels (p ≤ 0.01) in milk‐ and egg‐sensitized children. The correlation of TH2 responses with allergen‐specific antibodies would implicate polarized T cells in food allergic children in IgE hypersensitivity and overproduction of particular IgG subclasses alike. IgG1:IgG4 ratio declines with allergy sensitization and may denote emerging tolerance.     

Mucosal cell-mediated immunity to varicella zoster virus: role in protection against disease

By indirect immunofluorescence, enzyme-linked immunosorbent assay, and in vitro lymphocyte proliferation, we studied the antibody and cell-mediated immune response to varicella zoster virus (VZV) in serum, peripheral blood lymphocytes, and tonsillar lymphocytes in 49 children before and after tonsillectomy and adenoidectomy. Among the naturally infected patients seropositive for VZV antibody, most demonstrated VZV-specific proliferation in the peripheral blood and tonsillar lymphocytes, with activity consistently higher in the tonsillar lymphocytes. Several patients seronegative for VZV antibody and without a prior history of clinical chickenpox also manifested VZV-specific proliferation in the tonsillar lymphocytes, and less frequently in peripheral blood lymphocytes. Of these, six children with high levels of activity in tonsillar lymphocytes, with or without high levels in the peripheral blood lymphocytes, failed to develop disease after intimate exposure to VZV in family settings. On the other hand, three other subjects with little or no VZV-specific proliferative activity in the tonsillar lymphocytes developed disease after similar exposure to VZV. These observations suggest the development of VZV-specific mucosal cellular immunity after overt or inapparent exposure to VZV. The appearance of such immunity appears to have a protective role against reinfection even in the absence of detectable serum antibody.