Peanut oral immunotherapy modifies IgE and IgG4 responses to major peanut allergens - 27/12/12
, Jing Lin, PhD b, Michael Kulis, PhD a, , Zhiyan Fu, PhD b, Pamela H. Steele, MSN, CPNP a, , Stacie M. Jones, MD c, Amy M. Scurlock, MD c, Gustavo Gimenez, BSc b, Ludmilla Bardina, MSc b, Hugh A. Sampson, MD b, A. Wesley Burks, MD a, Corresponding author: Brian P. Vickery, MD, UNC Department of Pediatrics, CB#7231, Chapel Hill, NC 27599.Abstract |
Background |
Patients with peanut allergy have highly stable pathologic antibody repertoires to the immunodominant B-cell epitopes of the major peanut allergens Ara h 1 to 3.
Objective |
We used a peptide microarray technique to analyze the effect of treatment with peanut oral immunotherapy (OIT) on such repertoires.
Methods |
Measurements of total peanut-specific IgE (psIgE) and peanut-specific IgG4 (psIgG4) were made with CAP-FEIA. We analyzed sera from 22 patients with OIT and 6 control subjects and measured serum specific IgE and IgG4 binding to epitopes of Ara h 1 to 3 using a high-throughput peptide microarray technique. Antibody affinity was measured by using a competitive peptide microarray, as previously described.
Results |
At baseline, psIgE and psIgG4 diversity was similar between patients and control subjects, and there was broad variation in epitope recognition. After a median of 41 months of OIT, polyclonal psIgG4 levels increased from a median of 0.3 μg/mL (interquartile range [25% to 75%], 0.1-0.43 μg/mL) at baseline to 10.5 μg/mL (interquartile range [25% to 75%], 3.95-45.48 μg/mL; P < .0001) and included de novo specificities. psIgE levels were reduced from a median baseline of 85.45 kUA/L (23.05-101.0 kUA/L) to 7.75 kUA/L (2.58-30.55 kUA/L, P < .0001). Affinity was unaffected. Although the psIgE repertoire contracted in most OIT-treated patients, several subjects generated new IgE specificities, even as the total psIgE level decreased. Global epitope-specific shifts from IgE to IgG4 binding occurred, including at an informative epitope of Ara h 2.
Conclusion |
OIT differentially alters Ara h 1 to 3 binding patterns. These changes are variable between patients, are not observed in control subjects, and include a progressive polyclonal increase in IgG4 levels, with concurrent reduction in IgE amount and diversity.
Le texte complet de cet article est disponible en PDF.Key words : Peanut allergy, oral immunotherapy, IgE, IgG4, peptide microarray, epitope, B cell, antibody affinity
Abbreviations used : FDR, HSA, OIT, PBS-T, psIgE, psIgG4
Plan
| Supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases. |
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| Disclosure of potential conflict of interest: B. P. Vickery has received research support from the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID); the American Lung Association; Cephalon; the Foundation of the American College of Allergy, Asthma & Immunology (ACAAI); and the Thrasher Research Fund and has received consultancy fees from Mead Johnson. M. Kulis has received research support from the NIH/NIAID. S. M. Jones has received research support from the National Peanut Board, the NIH, and the Food Allergy & Anaphylaxis Network; is on the Food Allergy & Anaphylaxis Network medical advisory board; has received lecture fees from Abbott Nutrition International, the Kentucky Society for Allergy, Asthma & Immunology, the New England Allergy Society, the ACAAI, Indiana University Medical School and Riley Children’s Hospital, the Spanish Society of Allergy & Clinical Immunology (Madrid, Spain), and the Oregon Allergy Asthma & Immunology Society; is on the NIAID Safety Monitoring Committee and the Arkansas Medicaid Drug Review Committee; and participated in ad hoc review for the NIAID Study Section. H. A. Sampson has received research support and travel support from the NIAID; is on the Danone Scientific advisory board; has received consultancy fees from Allertein Therapeutics and Food Allergy Initiative; is employed by Mount Sinai Medical School; receives royalties from Elsevier-Wiley; and is a 42.5% owner of Herbs Springs, LLC. A. W. Burks has received research support and travel support from the NIH/NIAID; is on the board for the American Academy of Allergy, Asthma & Immunology (AAAAI), the Food Allergy & Anaphylaxis Network, the US Food and Drug Administration, the Journal of Allergy and Clinical Immunology, and the NIH/HAI; has received consultancy fees from Dannon Co Probiotics, Exploramed Development, Intelliject, McNeil Nutritionals, Merck & Co, Novartis, Nutricia, Pfizer, Portola Pharmaceuticals, and Schering-Plough; is employed by Duke University Medical Center and UNC North Carolina Children’s Hospital; has received research support from the Food Allergy & Anaphylaxis Network, the Food Allergy Initiative, the NIH, the National Peanut Board, Scientific Hospital Supplies (Nutricia North America), and the Wallace Research Foundation; has received royalties from UpToDate; has received payment for developing educational presentations from Current Views; has stock/stock options in Allertein and MastCell; and has received travel support from the AAAAI, the European Academy of Allergy & Clinical Immunology, and the ACAAI. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 1
P. 128 - janvier 2013 Retour au numéro
Article précédent
- Sublingual immunotherapy for peanut allergy: A randomized, double-blind, placebo-controlled multicenter trial
- David M. Fleischer, A. Wesley Burks, Brian P. Vickery, Amy M. Scurlock, Robert A. Wood, Stacie M. Jones, Scott H. Sicherer, Andrew H. Liu, Donald Stablein, Alice K. Henning, Lloyd Mayer, Robert Lindblad, Marshall Plaut, Hugh A. Sampson, Consortium of Food Allergy Research (CoFAR)
- Identifying infants at high risk of peanut allergy: The Learning Early About Peanut Allergy (LEAP) screening study
- George Du Toit, Graham Roberts, Peter H. Sayre, Marshall Plaut, Henry T. Bahnson, Herman Mitchell, Suzana Radulovic, Susan Chan, Adam Fox, Victor Turcanu, Gideon Lack, Learning Early About Peanut Allergy (LEAP) Study Team
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