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Notes: Background: The role of neutrophils and myeloperoxidase (MPO) – assumed to be a marker of neutrophil activation – in bronchial asthma is still unclear, and the literature is controversial. Methods: To investigate the participation of neutrophils and their products in childhood asthma, we assessed neutrophil counts and serum MPO in 175 children with bronchial asthma. Ninety of them were asymptomatic, and 85 of them were symptomatic within the last 2 weeks before examination. Bacterial infection of the lower respiratory tract (LRTI) was present in 34 and viral infection in 49 patients. As controls, 45 patients with cystic fibrosis, 23 patients with bacterial LRTI, and 87 healthy children were recruited. Results: Median neutrophil counts (3135 cells/μl) and serum MPO levels (352 μg/l) were not different in children with bronchial asthma from healthy controls (2220 cells/μl and 401 μg/l, respectively), whereas in patients with cystic fibrosis and bacterial LRTI, neutrophil counts and MPO levels were increased. Asthmatic children with bacterial infection had significantly higher serum MPO and neutrophil counts then asthmatic children with viral infection or without infection. In addition, a significant correlation was found between serum MPO and neutrophil counts and C-reactive protein (CRP), and between neutrophil counts and CRP, but no relationship was detected for serum MPO and disease activity or lung function. Conclusions: Our data indicate that serum MPO – a marker of neutrophil activation – does not contribute to the assessment of the inflammatory process in childhood asthma. In addition, measurement of serum MPO appears not to be useful in assessing the participation of the neutrophil in asthmatic children. However, assessment of MPO may be useful to distinguish between bacterial and viral infection. Abbreviations. BAL: bronchoalveolar lavage; CF: cystic fibrosis; CRP: C-reactive protein; ECP: eosinophil cationic protein; EPX: eosinophil protein X; LRTI: lower respiratory tract infection; MPO: myeloperoxidase.

Notes: In this study, deliberate sting challenge was investigated as a method for estimating the severity of anaphylactic reactions in bee venom-sensitized subjects. Twenty-one patients with previous anaphylactic reactions to field bee sting were subjected to a deliberate sting challenge (n = 32). To document anaphylactic reactions, plasma histamine levels were measured before, and then 1 and 2 min after, bee sting challenge. Eleven patients were re-challenged after 3–5 weeks. On 18 occasions, sting challenges caused no systemic reactions, in seven cases reactions were mild, in five moderate and in two severe. In all children showing systemic reactions, significant increases of plasma histamine were measured after 2 min. The results correlated significantly with clinical scores but not with skin prick test or with specific immunoglobulin E (IgE) and immunoglobulin G (IgG) antibodies against bee venom. In patients developing local reactions only, no increase of plasma histamine was detected. The relative amount of released histamine correlated significantly with the severity of clinical symptoms. Significant histamine release occured during the first 2 min after sting challenge in children with subsequent systemic reactions and the severity of these subsequent anaphylactic reactions correlated with plasma histamine concentrations. The measurement of plasma histamine levels in the first minutes after challenge test may therefore be used as an objective marker of a potential systemic reaction.

Notes: The coincidence of allergic sensitization was investigated in 302 school-aged children and their parents. Specific sensitization to four common inhalant allergens (grass and birch pollens, cat dander, Dermatophagoides pteronyssinus) was ascertained by means of skin-prick tests (SPT) carried out on the complete family unit at the beginning of a 22-month follow-up period. The same test procedure was then repeated on the children twice at 11-month intervals to provide cumulative prevalences of sensitization. A clinical history of atopy in the children (hay fever or asthma; n= 47), which was derived from an interview, is associated with sensitization (positive SPT in 89%). For three allergens (grass and birch pollens, cat dander) sensitization occurs significantly more frequently in the children of mothers who are sensitized to the same allergen (odds-ratios (ORs), 2.5–4.1). Additionally, in three of the four explanatory models related to a single antigen, maternal sensitization to one of the complementary allergens is of importance (ORs, 2.7–3.7). In contrast to this finding, none of the paternal sensitizations has statistical significance. Based on a reaction to at least one of the four allergens, the child's relative risk to be sensitized is increased in case of maternal (OR, 2.88; P= 0.001) but not of paternal (OR, 1.06; P= 0.83) sensitization. In conclusion, our data indicate that the maternal status is more predictive than that of the father with regard to the child's risk of sensitization.

Notes: The skin prick test (SPT) is a commonly used procedure for assessing a specific sensitization. The longitudinal variability of test results is of interest for clinical as well as epidemiological investigations. The sensitization to four common aeroallergens (grass pollen, birch pollen, Dermatophagoides pteronyssinus, cat dander) is investigated within the framework of three consecutive SPTs at 11-month intervals for a population of 587 schoolchildren. The prevalence of sensitization based on a weal diameter of at least 2 mm was between 12.9% (cat dander) and 23.9% (grass pollen) in the initial testing. The positive predictive values of the initial SPT were between 75.3% (birch pollen) and 88.2% (cat dander) for the two subsequent SPTs. In the case of initially negative tests with positive second and third SPTs the incidence ranged between 3.2% (cat dander) and 4.3% (birch pollen) per year. A clear increase in the intensity of reaction in subsequent tests was observed in a number of probands testing positively in the initial SPT. In conclusion, our data indicate a high long-term stability of a specific sensitization to aeroallergens in SPT.

Notes: Venom-specific IgE and IgG antibodies were measured in the sera of bee-venom-sensitive patients during a 3-year hyposensitization period. The level of specific IgG antibodies initially increased, and 2 months after the start of therapy, this increase was on average five-fold. A concomitant hut non-significant increase in specific IgE antibodies was also observed initially. Later during the treatment period specific IgE antibodies showed a continuous decline and after 3 years the level was one third of the pre-treatment level. Venom-specific IgG antibodies, however, remained above the pre-treatment level. The disappearance of the severe allergic reactions was related to the level of both IgE and IgG antibodies as demonstrated in seventy-six bee sting challenges. In patients with specific IgG antibody levels above 400 u/ml, no severe reactions were observed even if the patient had levels of specific IgE- antibodies of RAST class 3 or 4. These data suggest that the relationship between venom-specific IgE and IgG antibodies permits an evaluation of the state of immunity to insect stings.

Notes: Abstract. Previous studies have suggested that, apart from IgE-mediated reactions, some of the symptoms of food allergy may be caused by IgG antibodies to food proteins. This study was carried out to see if there were any distinctive features of the IgG sub-class antibody response to dietary antigens which occurs in food allergic patients. IgG subclass antibodies were measured using a quantitative enzyme-linked immuno-sorbent assay (ELISA) to wheat gliadin, ovalbumin and bovine casein in twenty patients who had coeliac disease and in twenty-eight egg allergic patients. These were compared with twenty-one atopic dermatitis patients who did not have food allergy and twenty-six healthy control subjects. Coeliac disease patients tended to have raised IgG antibody levels (especially IgG1) to all three antigens but these overlapped considerably with that seen in egg allergic and atopic dermatitis patients.Coeliacs who avoided gluten had anti-gliadin antibody levels which did not differ from those seen in healthy subjects but nevertheless had raised anti-ovalbumin and casein-specific antibodies. The IgG antibody was largely restricted to IgG1 and IgG4 sub-class although the relative amount of each varied with the antigen. Although gliadin-specific antibodies were mainly IgG1, ovalbumin-specific antibodies were mainly IgG4. The increased antibody levels to all three antigens in coeliacs were caused by a raised IgG1 response, IgG4 antibodies were usually normal. Egg allergic patients also had raised IgG1 but not IgG4 antibodies to ovalbumin.These data show that the response to different dietary antigens can vary with the antigen. The fact that IgG1 and not IgG4antibodies were raised to all three antigens in patients with coeliac disease suggests that they are a secondary consequence of the disease, perhaps reflecting increased transport of antigens across a damaged gut mucosa rather than a specific immunopathological reaction. However, the observation that antibodies to gliadin, and not ovalbumin or casein, fell following gluten avoidance shows that the response to gliadin, at least, is dependent upon continued exposure to antigen.

Notes: The IgG sub-class antibody response to bee venom in the four sub-classes was investigated in ten patients during and after venom immunotherapy. All patients tolerated a bee sting challenge 1, 2 and 3 years after the start of treatment as well as 1 and 2 years after treatment was stopped. Anti-phospholipase A2 (PLA2) antibodies were of IgG1 and IgG4 sub-class and rose early in treatment, IgG1 anti-PLA2 fell to pre-treatment levels after 3 years in contrast to IgG4 anti-PLA2 levels, which remained high during maintenance therapy and declined relatively little in the 2 years after the termination of treatment. This data shows that IgG4 antibodies are maintained in the absence of monthly maintenance injections and suggests that they may provide long lasting clinical protection from insect stings.

Notes: Background Cellular proliferation to various allergens (Dermatophagoides pleronyssinus, β-lactoglobulin, bovine serum albumin, ovalbumin) has been found in cord blood cells. Whether this reflects a sensitization during foetal life is uncertain.Objective We studied the cellular reactivity and cytokine production of cord blood cells in response to cow's milk proteins in a randomely selected group of newborns. The delineation of possible in utero allergen contact was attempted.Objective Cord blood mononuclear cells from 39 neonates were incubated with cow's milk proteins (α-lactalbumin, β-lactoglobulin, casein, α-casein, β-casein, k-casein, bovine serum albumin) for 7 days, and proliferation was assessed by incorporation of [3H]thymidine. Cord blood cell-derived interferon-γ (IFNγ) and interleukin-4 (IL-4) secretion was evaluated in response to allergen or phytohaemagglutinin (PHA) stimulation.Results A pronounced proliferation of cells stimulated with α-lactalbumin (ALA; mean stimulation index 8.0, 95% confidence interval 5.2–10.8), β-lactoglobulin (BLG; mean stimulation index 5.9, 95% confidence interval 3.2–8.6) and α-casein (2.6, 95% confidence interval 2.9–9.1), as opposed to unstimulated cells in medium, was found. No correlation was found between cellular proliferation to milk proteins and parental atopy, maternal total IgE or cord blood IgE. IFNγ production (but not IL-4) was inducible by PHA (range 429–1810 pg/ml), but only in one individual upon stimulation with BLG. Preferentially, reduced IFNγ levels were found in individuals with positive parental allergic history.Conclusion The recognition of allergen by cord blood cells indicates that allergen priming must occur prenatally. The relevance for subsequent sensitization is unclear.

Notes: In an attempt to understand the role of the different IgG subclasses in allergic disease, we have studied the subclass of IgG antibody to dust mite (HDM) and grass pollen (GP) produced as a result of natural exposure. Studies were carried out on 40 atopic children and 100 atopic adults who had never received immunotherapy. Thirty-two non-atopic adult controls were also studied. The specificity of the assay for IgG antibodies to dust mite was confirmed by inhibition with the homologous extract but not mite culture medium or fetal calf serum. IgG1 antibodies to HDM could be detected in most atopics (94%) and non-atopics (97%), and similar results were obtained for GP (81% and 100%, respectively). IgG4 antibodies to HDM were detected in more atopics (66%) than non-atopics (53%) and the difference was more marked for GP (72% vs. 19%). While the levels of IgG1 antibodies were not significantly different in the two groups, the levels of IgG4 antibodies were much lower in the non-atopics (P 〈 0.001, Mann–Whitney U-test). These data show that all subjects were capable of recognizing and mounting an IgG1 antibody response to these inhaled antigens. Atopic individuals differed from normal subjects in the frequency with which they made IgG4 antibodies in response to natural exposure to both dust mites and pollen.

Notes: Twelve egg-allergic patients were selected on the basis of a clinical history of egg allergy and a positive skin-prick test (SPT) to whole egg. A study was then carried out on the ability of the patients’ washed leucocytes to release histamine in the presence of whole egg, ovomucoid, ovalbumin and ovotransferrin. Histamine release (HR) from washed leucocytes was demonstrated in ten out of twelve patients, but only four out of ten released over 40% of their total histamine. Spontaneous HR ranged from 2·1–14·5% with a mean of 7·5%. There was good agreement between positive and negative HR, skin test and radioallergosorbent test (RAST) results. Concordance between the HR and skin test was found in 83%, HR and RAST in 71% and skin test and RAST in 78% of patients. However there was poor quantitative agreement between these three tests. When skin-prick tests and HR thresholds were compared, ovomucoid elicited the greatest skin test sensitivity in five out of six patients, whereas five of the same six were more sensitive to ovalbumin when judged by HR.