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1.
Ann Allergy Asthma Immunol ; 118(3): 356-364.e3, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28087382

RESUMO

BACKGROUND: Egg oral immunotherapy is effective but time consuming. OBJECTIVE: To assess the efficacy and safety of egg rush oral immunotherapy (ROIT) with a targeted dose equivalent to a raw egg white. METHODS: Thirty-three persistent egg allergic children confirmed by double-blind, placebo-controlled food challenge (DBPCFC) were randomized to receive egg ROIT immediately after randomization (ROIT1 group), or to continue an egg avoidance diet for 5 months after randomization (control group [CG]). A 5-day build-up phase starting with the highest single tolerated dose at baseline DBPCFC was scheduled and several doses administered daily until achieving a dose of approximately 2,808 mg of egg white protein. In the maintenance phase, patients ate an undercooked egg every 48 hours for 5 months. The CG participants who failed the DBPCFC at 5 months began active treatment. Children from the ROIT1 group plus children from the CG who failed a second DBPCFC at 5 months and then received egg ROIT were randomized to the ROIT2 group. Adverse events (AEs) and immune marker evolution were recorded. RESULTS: A total of 17 (89%) of 19 children in the ROIT1 group and no CG patients were desensitized at 5 months (P < .001). A total of 31 (97%) of the 32 children in the ROIT2 group completed the build-up phase in a median of 3 days (range, 1-14 days), and 30 (94%) of 32 maintained desensitization at 5 months. From baseline to 5 months of treatment, skin prick test, specific IgE, and specific IgE/IgG4 ratio to egg fractions significantly decreased, whereas specific IgG4 increased. During the build-up phase, AEs occurred in 69% of patients (50% had ≤2 AEs) and 31% of doses (2% severe, 55% gastrointestinal). Lower threshold dose in the DBPCFC and higher egg white and ovalbumin specific IgE levels at baseline revealed an association with a higher rate of AEs. CONCLUSION: The proposed 5-day egg ROIT desensitized 94% of the allergic patients, with most AEs being mild or moderate.


Assuntos
Alérgenos/administração & dosagem , Alérgenos/imunologia , Dessensibilização Imunológica/métodos , Hipersensibilidade a Ovo/imunologia , Hipersensibilidade a Ovo/terapia , Ovos/efeitos adversos , Administração Oral , Adolescente , Biomarcadores , Criança , Pré-Escolar , Hipersensibilidade a Ovo/diagnóstico , Feminino , Seguimentos , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Fenótipo , Fatores de Risco , Resultado do Tratamento , Fluxo de Trabalho
2.
Int Arch Allergy Immunol ; 165(2): 83-90, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25359082

RESUMO

BACKGROUND: This paper reports the case of an egg-allergic pediatric patient who, once desensitized to egg following a successful rush oral immunotherapy protocol, could also tolerate Lizipaina®, a drug containing lysozyme (LYS) and papain, which had previously caused him a severe allergic reaction. Because the LYS amount that elicited the anaphylactic reaction (5 mg) was much lower than that tolerated during a double-blind placebo-controlled food challenge (corresponding to approximately 60 mg of LYS), the possibility that the presence of papain could increase the allergenic potential of LYS was investigated. METHODS: Lizipaina, LYS and LYS hydrolyzed with papain were analyzed by SDS-PAGE under reducing and nonreducing conditions, and Western blotting of sera from egg-allergic patients was performed in order to detect IgE-binding fragments. Finally, sequence identification of the IgE-reactive bands was carried out by MALDI-TOF/TOF. RESULTS: The SDS-PAGE pattern of LYS treated with papain under nonreducing conditions showed the presence of intact LYS that partially disappeared following reduction with ß-mercaptoethanol, releasing IgE-reactive fragments as determined by Western blotting. MALDI-TOF/TOF revealed that papain degraded LYS, giving rise to three IgE-binding fragments: LYS (22-129), LYS (34-96) and LYS (62-128) that likely remained linked through the disulfide bonds present in the LYS molecule. CONCLUSION: The combined administration of LYS with proteolytic enzymes such as papain may have developed a severe allergic reaction in the patient studied, underlining the importance of considering all the components and their interactions when drugs are to be consumed by allergic persons.


Assuntos
Anafilaxia/imunologia , Hipersensibilidade a Drogas/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Muramidase/imunologia , Papaína/imunologia , Adolescente , Sequência de Aminoácidos , Hipersensibilidade a Ovo/imunologia , Hipersensibilidade a Ovo/terapia , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Dados de Sequência Molecular , Muramidase/química , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia
3.
Pediatr Allergy Immunol ; 24(3): 263-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23551792

RESUMO

BACKGROUND: Raw and cooked eggs are used as allergens in oral food challenge (OFC). Raw egg is the best option, as it keeps proteins intact and retains their allergenicity, albeit microbiologically safe manipulation is difficult. Therefore, the use of dehydrated egg white (DEW) could improve the efficacy and safety profile of OFC. The aim of the study was to compare the allergenicity of DEW, a product that undergoes a double heat treatment (pasteurization and drying), with that of raw egg white (REW) and determine the efficacy of DEW in the diagnosis of egg allergy. METHODS: We conducted a prospective study of 40 egg-allergic patients who visited our outpatient clinic. Each patient underwent OFC with DEW and REW to determine the correlation between the tests. DEW and REW extracts were analyzed using SDS-PAGE. We compared the allergenicity of both extracts using IgE immunoblotting with a serum pool from patients with positive OFC results. RESULTS: Ten patients (25%) had positive OFC results with both DEW and REW, and the doses that triggered an allergic reaction in each patient were similar (p > 0.05). All 30 patients (75%) with a negative OFC result with DEW also had negative OFC results with REW. SDS-PAGE and IgE immunoblotting revealed that the protein composition and IgE-binding capacity of both extracts were virtually identical. CONCLUSIONS: This is the first time that it is shown that the allergenicity of commercially available DEW is equivalent to raw egg whites. In vivo and in vitro tests showed that processing of DEW does not affect the allergenicity of egg proteins. DEW is an effective and microbiologically safer source of allergen for the diagnosis of egg allergy. Furthermore, DEW can be used in egg oral immunotherapy.


Assuntos
Alérgenos , Dessensibilização Imunológica/métodos , Hipersensibilidade a Ovo/diagnóstico , Clara de Ovo , Adolescente , Alérgenos/uso terapêutico , Criança , Pré-Escolar , Dessensibilização Imunológica/normas , Dessecação , Hipersensibilidade a Ovo/imunologia , Hipersensibilidade a Ovo/terapia , Feminino , Humanos , Imunoglobulina E/metabolismo , Masculino , Estudos Prospectivos , Ligação Proteica , Reprodutibilidade dos Testes
4.
Pediatr Allergy Immunol ; 23(2): 128-32, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22432882

RESUMO

BACKGROUND: Cow's milk oral immunotherapy (CMOIT) is a recognized treatment for persistent cow's milk (CM) allergy. However, further data are necessary on tolerance to milk from other mammals. OBJECTIVE: To describe the clinical and immunologic features of goat's and sheep's milk (GSM) allergy in patients who tolerated CM after CMOIT. METHODS: Fifty-eight CM-allergic patients who successfully underwent CMOIT in our department were evaluated using skin prick test (SPT), specific immunoglobulin (Ig) E determination, enzyme-linked immunoassay (ELISA), and controlled oral challenge to assess allergy to GSM. Statistical analysis was carried out to identify markers of allergy to GSM. RESULTS: Fifteen of 58 (25.9%) patients were allergic to either goat's or sheep's milk or to both, as confirmed by a controlled positive oral challenge. Forty-seven percent of all positive oral challenges were classified as anaphylactic reactions. Specific IgE to CM casein, goat's whole milk, and sheep's whole milk was 13.2, 18.0, and 21.4 kU(A)/l in the group of GSM-allergic patients and 6.6, 6.5, and 6.5 kU(A) /l in the GSM-non-allergic patients (p < 0.05). Decision-making cut-off points based on sIgE for diagnosing symptomatic GSM allergy could not be determined. ELISA inhibition assays showed limited cross-reactivity (up to 77.2%) between CM casein and GSM casein in the group of GSM-allergic patients in contrast with almost 100% in GSM-not-allergic patients. CONCLUSION: We found a high prevalence (26%) of allergy to GSM in our population of CM-allergic children treated with oral immunotherapy. Therefore, tolerance to GSM should be assessed in order to provide accurate nutritional advice and minimize life-threatening accidental intake. Specific IgE to CM casein, goat's and sheep's whole milk is a good marker of this allergy. Although CM oral immunotherapy is a specific treatment for CM allergy, it may not be effective against allergy to the milk of other mammals.


Assuntos
Dessensibilização Imunológica , Hipersensibilidade a Leite/epidemiologia , Hipersensibilidade a Leite/etiologia , Hipersensibilidade a Leite/prevenção & controle , Administração Oral , Animais , Bovinos , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Cabras , Humanos , Masculino , Proteínas do Leite/efeitos adversos , Proteínas do Leite/imunologia , Prevalência , Ovinos , Testes Cutâneos
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