Induction of tolerance in humans: effectiveness of oral and nasal immunization routes.
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Administration, Intranasal↗
Biomedical subjects
S Husby
Publications and source records attributed to S Husby.
Increased proportions of bacteria capable of cleaving IgA1 in the pharynx of infants with atopic disease.
Based on the observation that children with a history of atopic disease show significantly increased levels of cleaved secretory IgA in nasopharyngeal secretions, we have previously formulated the hypothesis that bacteria-induced local deficiencies of the immune barrier of the upper respiratory tract may be a contributing factor in the development and perpetuation of atopic diseases. To evaluate this hypothesis, 25 infants were subjected to clinical, bacteriologic, and immunologic examination at the age of 18 mo, 30 mo, and 5 y. The 11 infants, who showed clinical and immunologic evidence of atopic disease at the age of 18 mo, harbored significantly higher proportions of IgA1 protease-producing bacteria (median, 36%; range, 14-64%) than the 14 healthy infants (median, 5%; range, 0.4-14%). No statistically significant differences were observed at the two subsequent examinations, but healthy children showed a statistically significant increase in proportions of IgA1 protease-producing bacteria in the pharynx with increasing age. IgA1 protease-producing bacteria detected included Streptococcus mitis biovar 1, Haemophilus influenzae, Haemophilus parahaemolyticus, Streptococcus pneumoniae, and Neisseria meningitidis, of which the first mentioned species was mainly responsible for the difference observed at the 18-mo examination. Percentage proportions of IgA1 protease-producing bacteria were significantly related to passive smoking which may stimulate the premature and more pronounced pharyngeal colonization of the atopic infants with the IgA1 protease-producing variant of S. mitis biovar 1. The results of the study support the hypothesis that IgA1 protease-producing bacteria colonizing the upper respiratory tract jeopardize the local immune barrier and, thereby, may facilitate the penetration of potential allergens resulting in atopic disease.
Bacterial Infections↗
Oral tolerance in humans: T cell but not B cell tolerance to a soluble protein antigen.
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Administration, Oral↗
[Pseudocroup treated with inhaled steroid (budesonide). A double-blind placebo-controlled trial].
The aim of this prospective, randomised, double blind study was to evaluate whether inhaled nebulized corticosteroid is effective in the treatment of croup. Thirty-seven children (aged 0.4-4.9 years) admitted to hospital with moderate to severe croup were allocated to treatment with either 2 mg nebulized budesonide (20) or saline (17). Disease severity was assessed by a clinical croup score based on stridor, cough, retractions, dyspnoea and cyanosis, and the overall clinical assessment was scored on a visual log scale (0-100). Two hours after treatment there was a significant improvement in croup score in the group treated with budesonide (8 to 4.5), but not in the group treated with saline (8 to 8). Furthermore, the overall clinical assessment score decreased significantly (50 to 25) in the group treated with budesonide, whereas it remained constant in the placebo group (60 to 62). The results indicate that nebulised budesonide can be used as a safe and effective alternative treatment in children with moderate to severe croup.
Administration, Inhalation↗
Oral tolerance in humans. T cell but not B cell tolerance after antigen feeding.
The purpose of this study was to investigate whether oral tolerance, defined as Ag-specific immunologic unresponsiveness after Ag feeding, could be induced in humans after prolonged Ag ingestion. Eight adult volunteers ingested a total dose of 0.5 g of keyhole limpet hemocyanin (KLH) followed by subcutaneous immunization with KLH. Eight controls received only the subcutaneous immunization. In the group fed KLH, there was a significant reduction in KLH-specific T cell proliferation (p = 0.04) and delayed skin test responses (p = 0.07) to KLH. KLH ingestion alone did not induce significant levels of Abs in either serum or secretions. However, after the subsequent subcutaneous immunization, the number of circulating IgG and IgM anti-KLH-producing cells, the titers of serum IgG, IgA, and IgM anti-KLH Abs, and the titers of IgA anti-KLH Abs in saliva and intestinal secretions were significantly greater in the KLH-fed group than in the nonfed group. We conclude that KLH feeding induced systemic T cell tolerance, but B cell priming, at both systemic and mucosal sites. These studies support the concept of using Ag feeding as a treatment for certain immune-mediated diseases.
Administration, Oral↗
Suppression of the immune response by nasal immunization.
Intranasal immunization results in both a mucosal and a systemic immune response in humans. Intranasal tetanus toxoid immunization in humans causes an increased serum IgA1 antibody response to tetanus toxoid following a subsequent intramuscular immunization. We hypothesized that intranasal priming with a novel protein antigen, keyhole limpet hemocyanin (KLH), would similarly result in an up-regulated systemic IgA response after a subsequent systemic immunization. To test this hypothesis, five healthy adults received a primary series of intranasal KLH immunizations followed 3 months later by a subcutaneous KLH immunizations Eight healthy adults received only a subcutaneous KLH immunization and served as controls. The nasal immunization resulted in a brisk and sustained serum IgM, IgA, and IgG antibody response and a mucosal IgA response. The subcutaneous immunization alone resulted in a serum antibody response and the development of delayed type hypersensitivity by skin testing. When the nasally primed subjects received a subsequent subcutaneous immunization there was a decline in the serum concentration of IgA and IgG antibodies to KLH. In addition, the nasally primed subjects failed to develop delayed type hypersensitivity to KLH following subcutaneous immunization. These data suggest that the nasal mucosa can induce a mucosal and systemic response; however, it may also suppress a subsequent immune response to systemic immunization.
Administration, Intranasal↗
Treatment of croup with nebulised steroid (budesonide): a double blind, placebo controlled study.
The aim of this prospective, randomised, double blind study was to evaluate whether nebulised local steroid treatment is effective in the treatment of croup. Thirty six infants and children (0.4-4.9 years of age) admitted to hospital with moderate to severe croup were allocated to receive either 2 mg nebulised budesonide (20 children) or saline (16 children). Disease severity was assessed by a clinical total croup score based on stridor, cough, retractions, dyspnoea, and cyanosis. In addition the overall clinical impression was evaluated (0-100). Two hours after treatment there was a significant improvement in the total croup score in the group treated with budesonide (8 to 4.5), but not in the group treated with saline (8 to 8). Furthermore, the overall clinical impression assessment score decreased significantly (50 to 25) in the group treated with budesonide, whereas it remained constant in the placebo group (60 to 62). The total croup score and overall clinical severity were significantly better in the group treated with budesonide than in the placebo group. No side effects were observed. The results indicate that nebulised budesonide can be used as a safe and effective alternative treatment in children and infants with moderate to severe croup.
Bronchodilator Agents↗
Gm allotypes as indicators of non-atopic and atopic bronchial asthma.
69 Caucasian children, 34 with non-atopic and 35 with atopic bronchial asthma, demonstrated different, Gm-associated IgG antibody responsiveness. The non-atopic bronchial asthma group showed a preponderance of the Gm(a,'',g) haplotype, while the atopic study group showed a preponderance of the haplotype with the alternative allotypes on all IgG subclass loci, namely Gm(f,n,b). Patients with non-atopic bronchial asthma showed a significantly increased frequency of the phenotypes containing the Gm(a,'',g) haplotype, namely the Gm(a,'',g/a,'',g) and Gm(a,'',g/f,'',b), and an increased number of individuals were homozygous G2m('','') on the IgG2 locus. The 2 asthma groups showed different characteristic IgG subclass patterns, the non-atopic group with significantly decreased IgG2 and IgG3, especially those of the Gm(a,'',g/a,'',g) phenotype, and the atopic group with significantly increased IgG1 and IgG4, especially those of the Gm(f,n,b/f,n,b) phenotype. The characteristic IgG subclass patterns originate from the different Gm phenotypes found in the 2 groups. The results emphasize the presence of qualitatively and quantitatively different IgG molecules in non-atopic and atopic bronchial asthma patients and show the interest in studying IgG genes and IgG molecules as markers of pathogenesis. G2m('','') homozygosity is a new important marker of non-atopic bronchial asthma.
Adolescent↗
IgG subclass antibodies to dietary antigens in IgA deficiency quantification and correlation with serum IgG subclass levels.
IgG subclasses of antibodies to the dietary antigens ovalbumin, beta-lactoglobulin, casein, bovine IgM, and glycgli (a gluten component) were quantified in 20 adults and 10 children with IgA deficiency and healthy controls (21 adults and 7 children). In the IgA-deficient subjects the levels of IgG subclasses in serum were determined. Detectable antibody levels were observed in the majority of the subjects in IgG1 and IgG4 for anti-ovalbumin and beta-lactoglobulin, and in IgG1, followed by IgG2, IgG3, and IgG4 for antibodies to casein, bovine IgM, and glycgli. Levels of IgG1 and IgG2 antibodies to bovine IgM were higher in the IgA-deficient adults than in controls (P less than 0.00005, P = 0.0007, respectively), whereas the other antibody levels did not differ significantly between the two groups. An analysis of correlation between the IgG subclass antibody levels did not provide evidence for a particular IgG subclass antibody response pattern against different protein antigens within the single individual. Serum IgG4 levels correlated positively with the summed IgG4 antibody levels (Spearman's p = 0.673, P = 0.0051). The IgA-deficient subjects, when compared with healthy controls, did not show a particular IgG subclass pattern or restriction of antibodies to dietary antigens.
Adolescent↗
Prospective estimation of IgG, IgG subclass and IgE antibodies to dietary proteins in infants with cow milk allergy. Levels of antibodies to whole milk protein, BLG and ovalbumin in relation to repeated milk challenge and clinical course of cow milk allergy.
Prospectively, serum levels of IgE, specific IgE antibodies (AB) to whole cow milk protein (CMP), bovine se-albumin, bovine immunoglobulin, bovine lactoferrin, bovine lactalbumin and beta-lactoglobulin (BLG), IgG and IgG subclass antibodies to ovalbumin (OA) and BLG, and IgG4 RAST to CMP (bovine whey) were measured in 39 infants with cow milk protein allergy (CMPA) at birth (cord blood), at time of diagnosis and before and after milk challenge at the age of 12 months. Immunological measurements were also undertaken in 33 control infants without CMPA at birth, at 6 months and at 18 months. At no time, were differences found between the levels of IgG and IgG subclass AB to OA and BLG in control versus infants with CMPA. In the 39 infants with CMPA no correlation was found between the levels of IgE, IgG and IgG subclass AB in cord blood and subsequent levels of these values, irrespective of the type of CMPA (IgE-mediated (CMA) or non-IgE-mediated (CMI)), and irrespective of whether remission had occurred. In cord blood 25/33 (76%) of the infants with CMPA had specific IgE-AB to one or more of the bovine milk proteins indicating a prenatal intrauterine sensitization to cow milk protein. At 6 months the frequency of specific IgE-AB to bovine milk proteins was significantly (p less than 0.05) higher in infants with CMA versus CMI, and at 12 months total serum-IgE and the increase of these specific IGE-AB and RAST to CMP were significantly higher (p less than 0.05) in infants with persistent CMA. From 6 to 12 months withholding milk resulted in a significant fall in specific IgE-AB to CMP, and IgG, IgG1 and IgG4 anti-BLG followed by an increase after milk challenge. Decreasing levels of IgG anti-OA from birth to 6 months reflect passive maternal transfer of IgG through the placenta, and increasing levels of IgG anti-BLG, already from birth to 6 months, may represent an early exposure to CMP in all infants. Significantly higher levels (p less than 0.05) of IgG anti-OA AB, IgG1 and IgG4 anti-BLG AB were found in infants with persistent CMA, indicating a close relation between the synthesis of IgE and IgG and between IgE and IgG subclasses (IgG1 and IgG4) in symptomatic cow milk-allergic individuals.(ABSTRACT TRUNCATED AT 400 WORDS)
Child, Preschool↗
Cord blood IgE. I. IgE screening in 2814 newborn children.
Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1-year birth cohorts (1983-1984 and 1985-1986) in Denmark (n = 1189 + 1625). 48.6% of the sera contained less IgE than the detection limit 0.1 kU/l. Cord blood IgE values greater than or equal to 0.5 kU/l were regarded as elevated. 13.2% of the sera contained at least 0.5 kU/l of IgE, with a significant preponderance in boys. Geometric mean cord blood IgE was 0.13 kU/l and 0.12 kU/l, respectively. Geometric mean cord blood IgE was significantly higher in boys. A significant seasonal variation with lowest IgE values in the autumn was found. No correlation between cord blood IgE and birth weight or gestational age was demonstrated. Only few newborns had cord blood IgA values greater than 0.014 g/l, calculated as geometric mean cord blood IgA + 2 SD among children with no detectable cord blood IgE, indicating infrequent contamination with maternal blood.
Cohort Studies↗
Cord blood IgE. II. Prediction of atopic disease. A follow-up at the age of 18 months.
Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1-year birth cohorts (1983-1984 and 1985-1986) in Denmark (n = 1189 + 1625). For follow-up we chose all infants with cord blood IgE greater than or equal to 0.5 kU/l and a randomly chosen group of the same size with cord blood IgE less than 0.5 kU/l. A total of 762 infants were clinically evaluated at 18 months of age. A diagnosis of definite atopy, probable atopy or no atopy, including both IgE and non-IgE mediated disease was established. Applying different cord blood IgE cut-off values (0.3, 0.5, 0.8, 1.1) we did not find an excess of atopic infants among those with elevated cord blood IgE irrespective of the chosen cut-off value. Atopic predisposition or family history of atopic disease was defined as at least one parent or older sibling with atopic disease. Significantly more infants with a family history developed atopy at 18 months. In the 2 series the positive predictive values of cord blood IgE greater than or equal to 0.5 were 43% and 46% and the sensitivities were 17% and 15%. The predictive values of having a family history were 48% and 44% and the sensitivities were 55% and 58%.
Cohort Studies↗
Cord blood IgE. III. Prediction of IgE high-response and allergy. A follow-up at the age of 18 months.
Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1-year birth cohorts (1983-1984 and 1985-1986) in Denmark (n = 1189 + 1625). For follow-up we chose all infants with cord blood IgE greater than or equal to 0.5 kU/l and a randomly chosen group of the same size with cord blood IgE less than 0.5 kU/l. A total group of 762 infants were clinically evaluated at 18 months of age, and in 688 of these we evaluated total and specific IgE. A diagnosis of definite atopy, probable atopy or no atopy was established. In the present study we defined allergic disease as atopic disease combined with elevated total IgE. We found a statistically significant correlation between cord blood IgE and IgE at 18 months of age. Significantly more infants with elevated cord blood IgE had developed allergic disease at 18 months. A cut-off value of 0.3 kU/l for cord blood IgE was superior to the originally suggested 0.5 kU/l. Significantly more infants with elevated cord blood IgE had developed specific IgE antibodies at 18 months. The most frequent specific IgE antibody was towards cow's milk. Specific IgE antibodies were very rarely found when total IgE was not elevated. A total IgE at the age of 18 months greater than 26 kU/l could be regarded as elevated. With regard to allergic disease the positive predictive values of cord blood IgE greater than or equal to 0.3 kU/l in the 2 series were 21% and the corresponding sensitivities 67% and 46%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Characterization of cow milk proteins in human milk: kinetics, size distribution, and possible relation to atopy.
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Animals↗
Recurrent wheezing in relation to environmental risk factors in infancy. A prospective study of 276 infants.
Clinical course and environmental factors were recorded in a prospective study of 276 unselected infants followed from birth to the age of 18 months. The study was performed with a questionnaire at the age of 6 and 12 months and a physical examination at 18 months. Fifty-nine (21%) of the children had greater than or equal to 2 episodes of wheezing before they were 18 months old. A total of 58 (21%) of the children belonged to the lowest social class V, 182 (66%) were daily exposed to passive tobacco smoking at home and/or in daycare, 164 (59%) were breastfed greater than or equal to 3 months, 192 (70%) were in daycare, 62 (22%) lived in flats and 167 (61%) were in daily contact with furred pets at home and/or in daycare. In social class V a preponderance of children were exposed to passive tobacco smoking, a majority were living in flats and a minority were breastfed greater than or equal to 3 months. Linear logistic regression analysis was used for the purpose of assessing the causal effect of environmental risk factors on the risk of recurrent episodes of wheezing before the age of 18 months. The study demonstrated that male sex and daily exposure to passive tobacco smoking were significant risk factors with estimated odds ratios 1.9 and 2.4, respectively. Maternal tobacco smoking seemed to be associated with the highest risk. There was a tendency--though not significant--indicating that breastfeeding greater than or equal to 3 months had a protective effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Cohort Studies↗
Intestinal perforation in a two-year-old child with eosinophilic gastroenteritis.
A two-year-old boy underwent a laparatomy for an intestinal perforation due to eosinophilic gastroenteritis. He had marked peripheral blood eosinophilia and a small duodenal biopsy showed heavy eosinophilic infiltration in the mucosa. After 1 1/2 year on a restricted diet, a control duodenal biopsy showed only slight eosinophilia. Perforation of the small intestine is a rare but serious complication in eosinophilic gastroenteritis.
Child, Preschool↗
Bovine beta-lactoglobulin in human milk from atopic and non-atopic mothers. Relationship to maternal intake of homogenized and unhomogenized milk.
Human milk samples (n = 300) were collected during a 3-week period from 10 healthy mothers and from 10 atopic mothers, all with healthy, solely breast-fed infants. The milk samples were analysed by an enzyme-linked immunosorbent assay (ELISA) for the content of bovine beta-lactoglobulin (BLG). In a cross-over design the atopic and non-atopic mothers alternated their intake of milk between homogenized and unhomogenized milk each week. On day 7, in each week, consecutive milk samples were taken before and 4, 8, 12 and 24 hr after a single ingestion of 500 ml of homogenized or unhomogenized milk. Detectable amounts of BLG (0.9-150 micrograms/l, median value 4.2 micrograms/l) were measured in 19/20 of the mothers (95%), in 9 of 10 atopic mothers and in all 10 of 10 non-atopic mothers. No correlation was found between the type of milk preparation (homogenized or unhomogenized) and the presence of BLG or the level of BLG in human milk. A great intra-individual and inter-individual variation of BLG level was found, and no relationship was observed between BLG levels and atopic status of the mothers. The interval between ingestion of 500 ml of milk and the maximal concentration of BLG on milk-free diet varied between 4 and 24 hr, median value 8 hr. The presence of BLG in human milk is a common finding in both atopic and non-atopic mothers.
Adult↗