Peanut oral immunotherapy modifies IgE and IgG4 responses to major peanut allergens

• Published in: Journal of allergy and clinical immunology Vol. 131; no. 1; pp. 128 - 134.e3
• Main Authors: Vickery, Brian P., Lin, Jing, Kulis, Michael, Fu, Zhiyan, Steele, Pamela H., Jones, Stacie M., Scurlock, Amy M., Gimenez, Gustavo, Bardina, Ludmilla, Sampson, Hugh A., Burks, A. Wesley
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 2013; Elsevier
• Subjects: Administration, Oral; Adolescent; Allergens; Allergens - administration & dosage; Allergens - immunology; Allergic diseases; Allergy and Immunology; antibodies; antibody affinity; Antibody Affinity - immunology; Ara h 1 antigen; Ara h 2 antigen; Arachis - immunology; Arachis hypogaea; B cell; B-lymphocytes; Biological and medical sciences; blood serum; Child; Child, Preschool; Desensitization, Immunologic; Digestive allergic diseases; epitope; Epitopes; Epitopes - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Hypersensitivity; IgE; IgG4; Immunoglobulin E; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunopathology; Immunotherapy; Infant; Lymphocytes B; Medical sciences; microarray technology; Nuts; oral immunotherapy; patients; Peanut allergy; Peanut Hypersensitivity - immunology; Peanut Hypersensitivity - therapy; peanuts; peptide microarray; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; IgE; IgG4; oral immunotherapy; antibody affinity; peptide microarray; PBS-T; B cell; FDR; Peanut allergy; HSA; psIgG4; OIT; psIgE; epitope; Human serum albumin; PBS containing 0.05% Tween 20; IgG 4; psIgG 4; False discovery rate; Peanut-specific IgE; Peanut-specific IgG 4; Food allergy; Antigenic determinant; Peptides; IgG; Immunology; Immunotherapy; Peanut; Immunopathology; Immunoglobulins; Antibody; Oral administration; B-Lymphocyte; Treatment; Digestive diseases; Affinity; Groundnut; Allergen
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2012.10.048

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. We used a peptide microarray technique to analyze the effect of treatment with peanut oral immunotherapy (OIT) on such repertoires. 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. 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. 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.