RESUMO
BACKGROUND: Birch pollen-related soya allergy is mediated by Gly m 4. Conformational IgE epitopes of Gly m 4 are unknown. OBJECTIVE: To identify the IgE epitope profile of Gly m 4 in subjects with birch pollen-related soya allergy utilizing an epitope library presented by Gly m 4-type model proteins. METHODS: Sera from patients with (n = 26) and without (n = 19) allergy to soya as determined by oral provocation tests were studied. Specific IgE (Bet v 1/Gly m 4) was determined by ImmunoCAP. A library of 59 non-allergenic Gly m 4-type model proteins harbouring individual and multiple putative epitopes for IgE was tested in IgE binding assays. Primary, secondary and tertiary protein structures were assessed by mass spectrometry, circular dichroism and nuclear magnetic resonance spectroscopy. RESULTS: All subjects were sensitized to Gly m 4 and Bet v 1. Allergen-specific serum IgE levels ranged from 0.94 to > 100 kUA /L. The avidities of serum IgE were 5.06 ng (allergic) and 1.8 ng (tolerant) as determined by EC50 for IgE binding to Gly m 4. 96% (46/48) of the protein variants bound IgE. Model proteins had Gly m 4-type conformation and individual IgE binding clustered in six major surface areas. Gly m 4-specific IgE binding could be inhibited to up to 80% by model proteins harbouring individual IgE binding sites in an epitope-wise equimolar fashion. Receiver operating curve analysis revealed an area under fitted curve of up to 0.88 for model proteins and 0.66 for Gly m 4. CONCLUSION AND CLINICAL RELEVANCE: Serum levels and avidity of Gly m 4-specific IgE do not correlate with clinical reactivity to soya. Six IgE-binding areas, represented by 23 amino acids, account for more than 80% of total IgE binding capacity of Gly m 4. Model proteins may be used for epitope-resolved diagnosis to differentiate birch-soya allergy from clinical tolerance.
Assuntos
Antígenos de Plantas/imunologia , Mapeamento de Epitopos , Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Imunoglobulina E/imunologia , Modelos Moleculares , Conformação Proteica , Sequência de Aminoácidos , Especificidade de Anticorpos/imunologia , Antígenos de Plantas/química , Antígenos de Plantas/genética , Betula/imunologia , Reações Cruzadas/imunologia , Mapeamento de Epitopos/métodos , Variação Genética , Humanos , Hipersensibilidade/imunologia , Tolerância Imunológica , Imunoglobulina G/imunologia , Pólen/imunologia , Ligação Proteica/imunologia , Curva ROC , Proteínas RecombinantesRESUMO
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Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Alho/efeitos adversos , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/terapia , Espectrometria de Massas/instrumentação , Espectrometria de Massas/tendências , Espectrometria de Massas , Espectrometria de Massas/métodos , Hipersensibilidade Imediata/diagnóstico , Imunoglobulina E , Imunoglobulina E/imunologia , Anafilaxia/complicações , Anafilaxia/diagnósticoAssuntos
Anafilaxia/imunologia , Liases de Carbono-Enxofre/imunologia , Hipersensibilidade Alimentar/imunologia , Alho/imunologia , Anafilaxia/complicações , Hipersensibilidade Alimentar/complicações , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/imunologia , Omeprazol/uso terapêutico , Inibidores da Bomba de Prótons/imunologia , Inibidores da Bomba de Prótons/uso terapêutico , Rinite Alérgica Sazonal/complicaçõesRESUMO
Long-wavelength UVA (340-400 nm UVA-1) phototherapy has been reported to be effective in atopic dermatitis, localized scleroderma and T-cell-derived skin diseases. We retrospectively investigated 70 patients with acute cutaneous GVHD after allogeneic haematopoietic cell transplantation or donor lymphocyte infusion. Complete and partial responses with a median duration of 10 months were achieved in 49 (70%) and 17 (24.3%) patients, respectively. Overall, 47 (67.1%) patients were not treated with systemic steroids. Furthermore, immunosuppression could be tapered in 24 (34.3%) patients while they were receiving UVA-1 treatment. Responses were seen irrespective of age or type of conditioning. Treatment was very well tolerated. After a median follow-up of 18 (range 10-60) months, three patients developed epithelial skin neoplasia. We conclude that UVA-1 therapy is feasible, well tolerated and can be an effective treatment for acute GVHD of the skin, thereby avoiding the use of systemic steroids and/or allowing a more rapid tapering of systemic immunosuppression in a substantial number of patients. The results of this retrospective analysis warrant larger, prospective studies and the effectiveness of UVA-1 therapy should be compared with other established treatment modalities.