Alexandra F Santos1,2,3,4, Nuno L Barbosa-Morais5, Barry K Hurlburt6, Sneha Ramaswamy4,7, Oliver Hemmings1,2,4, Matthew Kwok1,2,4, Colin O'Rourke8, Henry T Bahnson8, Hsiaopo Cheng6, Louisa James9, Hannah J Gould4,7, Brian J Sutton4,7, Soheila J Maleki6, Gideon Lack1,2,3,4. 1. Department of Women and Children's Health (Paediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK. 2. Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK. 3. Children's Allergy Service, Evelina London Children's Hospital, Guy's and St Thomas' Hospital, London, UK. 4. Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK. 5. Faculdade de Medicina, Instituto de Medicina Molecular João Lobo Antunes, Universidade de Lisboa, Lisbon, Portugal. 6. US Department of Agriculture, Southern Regional Research Center, New Orleans, LA, USA. 7. Randall Centre for Cell & Molecular Biophysics, King's College London, London, UK. 8. Benaroya Research Institute, Seattle, WA, USA. 9. Blizard Institute, Queen Mary University of London, London, UK.
Abstract
BACKGROUND: Understanding the discrepancy between IgE sensitization and allergic reactions to peanut could facilitate diagnosis and lead to novel means of treating peanut allergy. OBJECTIVE: To identify differences in IgE and IgG4 binding to peanut peptides between peanut-allergic (PA) and peanut-sensitized but tolerant (PS) children. METHODS: PA (n = 56), PS (n = 42) and nonsensitized nonallergic (NA, n = 10) patients were studied. Synthetic overlapping 15-mer peptides of peanut allergens (Ara h 1-11) were spotted onto microarray slides, and patients' samples were tested for IgE and IgG4 binding using immunofluorescence. IgE and IgG4 levels to selected peptides were quantified using ImmunoCAP. Diagnostic model comparisons were performed using likelihood-ratio tests between each specified nominal logistic regression models. RESULTS: Seven peptides on Ara h 1, Ara h 2, and Ara h 3 were bound more by IgE of PA compared to PS patients on the microarray. IgE binding to one peptide on Ara h 5 and IgG4 binding to one Ara h 9 peptide were greater in PS than in PA patients. Using ImmunoCAP, IgE to the Ara h 2 peptides enhanced the diagnostic accuracy of Ara h 2-specific IgE. Ratios of IgG4/IgE to 4 out of the 7 peptides were higher in PS than in PA subjects. CONCLUSIONS: Ara h 2 peptide-specific IgE added diagnostic value to Ara h 2-specific IgE. Ability of peptide-specific IgG4 to surmount their IgE counterpart seems to be important in established peanut tolerance.
BACKGROUND: Understanding the discrepancy between IgE sensitization and allergic reactions to peanut could facilitate diagnosis and lead to novel means of treating peanutallergy. OBJECTIVE: To identify differences in IgE and IgG4 binding to peanut peptides between peanut-allergic (PA) and peanut-sensitized but tolerant (PS) children. METHODS:PA (n = 56), PS (n = 42) and nonsensitized nonallergic (NA, n = 10) patients were studied. Synthetic overlapping 15-mer peptides of peanut allergens (Ara h 1-11) were spotted onto microarray slides, and patients' samples were tested for IgE and IgG4 binding using immunofluorescence. IgE and IgG4 levels to selected peptides were quantified using ImmunoCAP. Diagnostic model comparisons were performed using likelihood-ratio tests between each specified nominal logistic regression models. RESULTS: Seven peptides on Ara h 1, Ara h 2, and Ara h 3 were bound more by IgE of PA compared to PS patients on the microarray. IgE binding to one peptide on Ara h 5 and IgG4 binding to one Ara h 9 peptide were greater in PS than in PApatients. Using ImmunoCAP, IgE to the Ara h 2 peptides enhanced the diagnostic accuracy of Ara h 2-specific IgE. Ratios of IgG4/IgE to 4 out of the 7 peptides were higher in PS than in PA subjects. CONCLUSIONS: Ara h 2 peptide-specific IgE added diagnostic value to Ara h 2-specific IgE. Ability of peptide-specific IgG4 to surmount their IgE counterpart seems to be important in established peanut tolerance.
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