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Natural history of egg hypersensitivity.

Twenty-five children with clinical egg hypersensitivity, confirmed by double-blind challenge, were followed for between 2 and 2 1/2 years. Clinical egg hypersensitivity was fund to have resolved in 11 children but was persistent in 14. Skin prick tests reactions to egg were initially of equivalent size in the resolved and persistent groups, but became negative or diminished in size with resolution of clinical egg hypersensitivity, while remaining positive in the group with persisting symptoms. Symptoms after egg ingestion were categorised as cutaneous, gastrointestinal, respiratory, and angioedema. The adverse reactions of the resolved group were either cutaneous or gastrointestinal symptoms. The persisting group had multisystem involvement and most of them developed angioedema and respiratory symptoms. These differences may be useful as prognostic indicators in clinical egg hypersensitivity.

Child↗

Egg white-specific IgE and IgG subclass antibodies and their associations with clinical egg hypersensitivity.

The data obtained so far indicate that 1) presence of high titer of IgE antibodies was related with symptoms of egg hypersensitivity, 2) it seems unlikely that increased IgG4 antibody levels against egg white is a cause of egg hypersensitivity, and one should pay much attention to IgG1 antibodies, instead, 3) it is possible that increased IgG4 may reduce the effect of complement-fixing antibodies like IgG1 and/or interfere the action of IgE antibodies.

Adult↗

Egg hypersensitivity and adverse reactions to measles, mumps, and rubella vaccine.

We evaluated the safety of the measles-mumps-rubella (MMR) combination vaccine in 140 children with egg hypersensitivity. All children, regardless of vaccine skin test results or severity of egg hypersensitivity, were safely immunized with the MMR vaccine. Systemic reactions to MMR vaccine in two nonallergic children were documented, indicating that reactions unrelated to egg protein can occur. With the use of a competitive enzyme-linked immunosorbent assay, the standard MMR injection was found to contain approximately 37 pg of ovalbumin-like material. This study provides 95% confidence that at least 97.5% of egg-allergic children will tolerate MMR vaccine without significant difficulty. Skin testing was not found to be helpful in predicting an adverse reaction. We recommend that the American Academy of Pediatrics consider revising its current policy regarding skin test response to MMR vaccine and administration of MMR vaccine to egg-allergic children.

Anaphylaxis↗

Egg hypersensitivity and measles-mumps-rubella vaccine administration.

Because reports have described egg-sensitive individuals in whom anaphylaxis developed after measles vaccination, current recommendations include delaying administration of egg-derived vaccines until skin testing can be performed. Specifically, the 1988 Red Book recommends skin testing via scratch, prick, or puncture with 1:10 dilution of the vaccine and, if the result is negative, intradermal testing is suggested. The purpose of this study was to evaluate the likelihood of reaction to measles-mumps-rubella (MMR) vaccine in patients with documented egg sensitivity and to delineate the efficacy of skin-prick testing (SPT) to MMR as a predictor of hypersensitivity to the vaccine. Egg sensitivity was documented by initial SPT to egg and then, if possible, double-blind placebo-controlled food challenge (DBPCFC). Patients with a positive DBPCFC to egg or a history of anaphylactic egg sensitivity had a SPT with the MMR vaccine and then were given the MMR vaccine. Additionally, children with atopic dermatitis who had been previously proven egg sensitive via DBPCFCs were evaluated retrospectively for sensitivity to the MMR vaccine. Sixteen children with a history of egg sensitivity underwent SPT to egg, with a positive result 3 mm greater than the negative control found in 12 patients. Eight of these children had a positive DBPCFC to egg. The SPT to MMR vaccine was negative in all 16 children; vaccine administration followed with no resultant systemic problems. Three children had a local reaction at the site of injection. Twelve additional children with atopic dermatitis and egg sensitivity were reviewed. Each child had a positive SPT and DBPCFC to egg.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

EGG hypersensitivity as measured by RAST and a reverse enzyme-immunoassay.

The application of a reverse enzyme-immunoassay (REIA) to measure specific anti-egg IgE is described. The results obtained with the REIA and the RAST are shown. The REIA is economical, easy and fast to perform when the conjugate has been made, non-radioactive and offers a new alternative for the in vitro evaluation of egg white-specific IgE.

Antibody Specificity↗

[Allergenic activity of non-calcinated egg shell calcium].

BACKGROUND: There is few data to prove the safety of egg shell calcium as allergen. Especially, non-calcinated egg shell calcium is not allowed to use without the description of origin of egg on food labels in Japan. METHOD: We evaluated the possibly contaminated egg allergens in commercial non-calcinated egg shell calcium made from egg by in vitro methodologies (SDS-PAGE, western blotting, inhibition ELISA and sandwich ELISA) and by single-blind oral non-calcinated egg shell calcium challenge on 6 egg hypersensitivity patients. RESULTS: The allergenic activity of non-calcinated egg shell calcium was almost negligible compared to egg white by all in vitro methods. Furthermore, six patients with egg hypersensitivity were unresponsive to oral non-calcinated egg shell calcium challenge test. CONCLUSION: These results indicate that there is little contamination of egg white in non-calcinated egg shell calcium, and that the allergenic activity of non-calcinated egg shell calcium is equivalent to that of calcinated egg shell calcium.

Allergens↗

[The new criteria for skin prick test of atopic early infants--diagnosis for hypersensitivity of egg white].

To investigate the new criteria for skin prick test (SPT) of seventy-four atopic infants (2-5 months of age at the first visit, Mean 3.8 months, M:F = 54:20) to diagnose for hypersensitivity to egg white. It was classified into three groups by reaction type of SPT in the first visit. Group A were the infants who seemed only late (6 hours) or delayed (48 hours) reaction (n = 26). Group B were seemed immediate (15 minutes) and late or delayed reactions (n = 26), Group C were seemed only immediate reaction (n = 23). Atopic infants and controlled infants without no symptom but have any atopic disease a relative in the third degree, agreed to undergo SPT in the first visit, the prior were undergo 9-12 months of age, too. Serum total IgE (RIST), serum specific IgE antibody of egg white (EWRAST) and peripheral eosinophil counts in the blood (Eo. counts) were determined at the same time of SPT in atopic infants. The best criterion for SPT was the longest diameter of a erythema were greater than 3 mm at late and/or delayed reaction (Sensitivity: 100%, Specificity: 60%) in group A. Two third of infants in group. A were seemed immediate reaction and EWRAST levels were increased to larger than gread two at 9-12 months (p < 0.001). RIST levels and Eo. counts at the first visit were increased compared with the normal levels in the all groups, the prior and EWRAST levels in group B were higher than group A or C (p < 0.05, p < 0.05). RIST and EWRAST levels in group A at 9-12 months were higher than the first visit (p < 0.05, p < 0.01). In conclusion, SPT in atopic early infants were seemed several reactions at the first visit, but all reactions were useful for diagnose for hypersensitivity to egg white.

Dermatitis, Atopic↗

Recombinant IL-10 and IL-10/Fc treatment down-regulate egg antigen-specific delayed hypersensitivity reactions and egg granuloma formation in schistosomiasis.

In infection with the helminth Schistosoma mansoni, parasite eggs elicit a Th cell-mediated hepatic granulomatous inflammation that leads to scarring, portal hypertension, hemorrhage, and death. On the other hand, the cytokine IL-10 has been shown to decrease egg Ag-specific Th cell responses by down-regulating MHC class II as well as B7 costimulatory molecule expression on accessory cells. We now test the effect of IL-10 in vivo on models of egg Ag-specific hypersensitivity as well as on the natural disease. Systemic administration of IL-10 significantly inhibited delayed-type hypersensitivity reactions to egg Ag as well as primary and secondary granuloma formation to eggs embolized in the lung. However, significant inhibition of hepatic granuloma formation associated with the natural infection required the use of an IL-10/Fc fusion protein with a prolonged in vivo half-life. Lymph node cells from IL-10/Fc-treated mice produced less IL-2 and IFN-gamma, and more IL-4 and IL-10 than control cells, suggesting that reduced egg granuloma formation resulted primarily from down-regulation of Th1 responses. These results indicate that suitable administration of exogenous IL-10 can be effective in ameliorating immunopathologic damage associated with schistosomiasis.

Animals↗

Detection of four distinct groups of hen egg allergens binding IgE in the sera of children with egg allergy.

BACKGROUND: There appears to be a lack of agreement in the literature on the allergenicity of hen egg proteins. This may be partly due to the use of impure proteins in some cases. Egg yolk proteins have also been largely ignored in such studies. We therefore set out to determine, using especially purified proteins, their relative allergenicity, and to observe whether there were any relationships between their potency and the sensitivity of patients to them. METHODS AND RESULTS: The sera of 40 patients with clinically observed hen egg hypersensitivity were tested for specific IgE binding to purified egg white and egg yolk proteins using the radioallergosorbent test (RAST). Statistical treatment by correspondence analysis of the percent radioactive uptakes in the RAST to the 8 proteins demonstrated that there were four distinct groups of patients reacting in a similar way to four discrete sets of proteins. CONCLUSIONS: The first three sets of allergens consisted of egg white proteins as follows: firstly, lysozyme and ovalbumin; secondly, ovomucoid; and thirdly, ovomucin. The fourth set contained the egg white protein ovotransferrin and the egg yolk proteins apovitellenins I and VI and phosvitin. The existence of patient groups may explain why various workers have reported different allergens to be important in egg hypersensitivity. A sufficiently large number of patients must be examined so as to give a representative distribution across each group, otherwise the results may be biased towards one allergen.

Allergens↗

National Advisory Committee on Immunization (NACI). Supplementary statement MMR vaccine and anaphylactic hypersensitivity to egg or egg-related antigens.

The fourth edition of the Canadian Immunization Guide (1993) recommends that "persons who have a history of anaphylactic hypersensitivity to hens' eggs (urticaria, swelling of the mouth and throat, difficulty in breathing or hypotension) should not be given measles vaccine except under special precautions." The precautions outlined include skin testing with diluted vaccine and graded challenge vaccination if the skin test is positive. Results of several recent studies have questioned such a cautious approach. NACI has reviewed all available data and revised its guidelines accordingly. The following revised guidelines are a major departure from the previously published recommendations. They will appear in the next edition of the Canadian Immunization Guide. A measles-rubella combination vaccine (Mo-Ru Viraten Berna TM) recently licensed in Canada contains no avian proteins and therefore can be used without regard to egg allergy.

Anaphylaxis↗

Allergic reactions to measles (rubeola) vaccine in patients hypersensitive to egg protein.

We evaluated two children with allergy to egg-white protein (ovalbumin) who had generalized urticaria, angioedema, and respiratory difficulty after immunization with live rubeola vaccine. In both patients, serum IgE reactive with ovalbumin-related antigens in the vaccine was demonstrated. Subsequent evaluation of 24 children with ovalbumin allergy revealed that those who had positive ovalbumin skin tests, but no clinical reaction to egg white, were skin test negative on prick and intradermal testing with measles vaccine and were safely immunized. They had no detectable IgE directed against the rubeola vaccine, although IgE directed at ovalbumin was present. Six patients who had severe allergic hypersensitivity reactions on exposure to ovalbumin had IgE antimeasles vaccine antibody and had positive reactions after intracutaneous or intradermal testing with the vaccine. These patients were safely immunized with increasing volumes (0.05 ml increments every 20 minutes) of measles vaccine to receive the full dose. These studies suggest that children with severe allergic hypersensitivity to egg white should be screened with an intracutaneous test prior to immunization with measles vaccine; however, children who have positive skin tests but no clinical reaction to ovalbumin exposure are at minimal risk for hypersensitivity reactions to measles immunization, as previously reported.

Anaphylaxis↗

Allergenicity and antigenicity of chicken egg ovomucoid (Gal d III) compared with ovalbumin (Gal d I) in children with egg allergy and in mice.

When attempting to generate mouse monoclonal antibodies to hen's egg ovalbumin, injection of commercially purified ovalbumin resulted in monoclonal antibodies, which when assayed against commercially purified ovalbumin (Gal d I) or ovomucoid (Gal d III), appeared to be specific to both. With the use of high-performance liquid chromatography (HPLC)-repurified ovalbumin and ovomucoid in assay procedures, monoclonal antibodies generated by commercially purified ovalbumin were found to be specific for ovomucoid only. To clarify this phenomenon, mice were serially injected with commercially purified ovalbumin or HPLC-repurified ovalbumin. It was found that most of the antibody response to commercially purified ovalbumin was directed against the minor (< 1%) ovomucoid contaminant and that HPLC-repurified ovalbumin failed to produce antibodies to ovomucoid. Commercially purified ovomucoid resulted in only minimal amounts of antibodies to ovalbumin. Thus when commercially purified ovalbumin is used both for immunization and immunoassay, most of the antibodies produced are actually against the small amount of ovomucoid contaminant, and not ovalbumin. To determine whether ovomucoid is the major antigenic and allergenic egg white protein in human beings, one group of 18 children with egg allergy were skin prick tested with half-log dilutions of egg white extract and diethylaminoethyl cellulose (DEAE)-repurified ovomucoid, ovalbumin, and lysozyme. Ovomucoid mean wheal diameters were significantly greater than wheal diameters in response to ovalbumin, lysozyme, and egg white extract at the three most concentrated of five dilutions tested: 0.01, 0.03, and 0.1 mg/ml (p < 0.01). Serum ovomucoid-specific IgE and IgG antibody concentrations to DEAE-repurified ovomucoid were significantly greater than that to DEAE-repurified ovalbumin (p < 0.05). In a second study, 10 patients with egg allergy and persistent egg hypersensitivity were compared with 11 patients with egg allergy in whom clinical tolerance to egg developed. IgE antibodies to repurified ovomucoid were significantly greater in patients with persistent egg hypersensitivity compared with patients in whom clinical tolerance developed at the time of both initial and follow-up food challenges. In contrast, there were no significant differences in IgE antibody concentrations to repurified ovalbumin in either group at any time. These results suggest that ovomucoid is the immunodominant protein fraction in egg white and that the use of commercially purified ovalbumin has led to an overestimation of the dominance of ovalbumin as a major egg allergen and antigen in human beings.

Adolescent↗

Lung granulomatous hypersensitivity to eggs of Schistosoma japonicum in mice analysed by a radioisotopic assay and effects of hybridoma (idiotype) sensitization.

The radioisotopic assay for acute granulomatous hypersensitivity (AGH) to eggs of Schistosoma japonicum in mice sensitized with eggs in adjuvant has been examined in the high responder strain. C57BL/6. Responsiveness is expressed as the lung-kidney ratio of radioactivity in mice challenged intravenously with eggs and injected with 125I-iododeoxyuridine. Eggs vary in their AGH sensitizing and eliciting potency; eggs proven to be superior in the circumoval precipitation (COP) test for detection of human serum anti-S. japonicum antibodies are superior in the C57BL/6 AGH assay. CBA/H are non responders and BALB/c are low to intermediate responders and are thus different from C57BL/6 mice. Short-term infected CBA/H mice are low COP antibody responders relative to infected C57BL/6 and titres of IgM anti-egg antibodies are low in the CBA/H strain as determined in a solid-phase radioimmunoassay (RIA). Following egg sensitization, CBA/H mice are also lower responders than C57BL/6 mice in terms of antibodies with the specificity of a COP-positive IgM hybridoma-derived antibody, P.41, measured in a competitive RIA. No evidence has been obtained that alteration of the response to the target epitope of P.41 alters the responsiveness of C57BL/6 mice to S. japonicum eggs. Thus, large amounts of injected P.41 antibody do not alter lung AGH and induced anti-idiotype responses to the P.41 protein do not influence AGH in egg-sensitized C57BL/6 mice. However, immunization of C57BL/6 mice with another IgM anti-schistosome hybridoma antibody, 1.39, results in partial inhibition of lung AGH responsiveness. The nature of the effect of 1.39 immunization on AGH to eggs remains unknown, but further analysis of the phenomenon may lead to novel approaches to the control of granulomatous inflammatory disease in high responders.

Animals↗

Clinical significance of IgE-binding activity to enzymatic digests of ovomucoid in the diagnosis and the prediction of the outgrowing of egg white hypersensitivity.

BACKGROUND: We frequently encounter subjects without overt symptoms despite high IgE antibodies to egg white and its components. The measurements of these antibodies are not necessarily efficient for the diagnosis or the prediction of the outcome of egg allergy in children. METHODS: Specific IgE antibodies to egg white and its components, including ovomucoid, ovalbumin, ovotransferrin and lysozyme, were measured by direct RAST assays. IgE-binding activity to ovomucoid degraded by pepsin, trypsin and chymotrypsin was examined by RAST inhibition. Thirty subjects were divided into two groups with positive (n=18; mean age +/- SD = 42 +/-25 months) and negative (n=12; mean age +/- SD = 48 +/-31 months) oral challenge tests with egg white antigens. The individuals with positive results to the first challenge tests were given the second provocation tests at mean intervals of 32 months. IgE-binding activity of the sera collected on the first challenge to these ovomucoid fragments was compared between subjects with positive and negative reactions to the follow-up challenge tests. RESULTS: There were no significant differences in IgE antibody titers to egg white and its components between the positive and negative groups at the first and the second challenge tests. IgE-binding activity to ovomucoid digests after treatments with pepsin (p = 0.000008) and trypsin (p=0.037), except chymotrypsin (p=0.062), were significantly higher in subjects with positive challenge tests than in those with negative results. The difference was most remarkable in the IgE-binding to pepsin digests; the average concentrations (mean - SD and mean + SD) needed for 50% RAST inhibition in the positive group and in the negative group were 2.6 microg/ml (0.3 and 25) and 94.2 microg/ml (24.7 and 358.7), respectively. A significant difference was still observed in the inhibition tests using filtrates of pepsin digests with a membrane with MW 10,000 (p=0.014) and 3,000 (p=0.042) of cutoff. The concentration (mean= 0.8, mean - SD=0.2, mean + SD=3.4; microg/ml) of pepsin-treated ovomucoid required for 50% RAST inhibition in the subjects with positive second challenge results was significantly (p=0.033) lower than that (mean=6.8, mean-SD=0.6, mean + SD=73.9) of the negative group. CONCLUSION: IgE-binding activity to pepsin-digested ovomucoid was of diagnostic value to distinguish the challenge-positive subjects from the negative subjects. Subjects with high IgE-binding activity to pepsin-treated ovomucoid are unlikely to outgrow egg white allergy.

Adult↗

Role of IL-4 and IFN-gamma in Schistosoma mansoni egg-induced hypersensitivity granuloma formation. Orchestration, relative contribution, and relationship to macrophage function.

A well defined model of T cell-mediated hypersensitivity-type granulomatous inflammation induced by Schistosoma mansoni eggs was used to assess the role of IL-4 and IFN-gamma in granuloma development. Synchronized pulmonary granulomas were induced and isolated from S. mansoni-infected mice during vigorous (8 wk) and modulated (20 wk) stages of the disease. The sequential production of IL-4 and IFN was determined and related to temporal changes in granuloma macrophage production of IL-1, TNF, and superoxide anion (O2-). During the vigorous stage, IL-4 was produced on days 1 and 2 of granuloma formation, whereas IFN was released in greatest amounts on days 4 to 8. The peak of IL-4 occurred in a window between the peak of IL-1 (1 day) and maximal TNF production (8 to 16 days). Maximal O2- release tended to parallel IFN production. During the modulated stage when the inflammatory response is attenuated, IL-4 production was dramatically reduced as were levels of IL-1 and TNF, but IFN production persisted and maximum O2(-)-producing capacity was only delayed in onset. mAb specific for IL-4 and IFN were used to examine the effect of in vivo depletion of these cytokines on granuloma development. Administration of a single 1.0-mg dose of anti-IL-4 antibodies to mice with synchronously developing granulomas dramatically reduced granuloma size (40 to 50% suppression of area) during an 8-day study period, whereas antibodies to IFN had no effect on size. However, the latter treatment reduced giant cell formation. Our results indicate that granuloma development involves an orchestrated production of cytokines possibly resulting from sequential participation of different Th cell populations. Moreover, IL-4 is a pivotal cytokine in anamnestic cellular recruitment and subject to endogenous regulation.

Animals↗