Clinical efficacy and immune regulation with peanut oral immunotherapy

• Published in: Journal of allergy and clinical immunology Vol. 124; no. 2; pp. 292 - 300.e97
• Main Authors: Jones, Stacie M., Pons, Laurent, Roberts, Joseph L., Scurlock, Amy M., Perry, Tamara T., Kulis, Mike, Shreffler, Wayne G., Steele, Pamela, Henry, Karen A., Adair, Margaret, Francis, James M., Durham, Stephen, Vickery, Brian P., Zhong, Xiaoping, Burks, A. Wesley
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.08.2009; Elsevier; Elsevier Limited
• Subjects: Administration, Oral; Adolescent; Allergens - administration & dosage; Allergies; Allergy and Immunology; Apoptosis; Arachis - immunology; Basophils - immunology; Biological and medical sciences; Breastfeeding & lactation; Child; Child, Preschool; Cytokines - biosynthesis; Cytokines - immunology; Deoxyribonucleic acid; Desensitization, Immunologic - methods; DNA; Down-Regulation; Female; Food; Food allergies; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; IgE; IgG; IL-10; IL-5; immune tolerance; Immunoglobulin E - blood; Immunoglobulin G - blood; Immunopathology; immunotherapy; Infant; Male; Medical sciences; Microarray Analysis; Peanut hypersensitivity; Peanut Hypersensitivity - immunology; Peanut Hypersensitivity - therapy; Peanuts; Proteins; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Signal transduction; Skin Tests; T-Lymphocytes, Regulatory - immunology; Transcription factors; Treatment Outcome; IgE; FAB; Treg; IgG; apoptosis; IL-5; OFC; PBMC; IL-10; immune tolerance; Peanut hypersensitivity; MIP; SPT; immunotherapy; OIT; FoxP3; Oral food challenge; Facilitated allergen binding; Skin prick test; Oral immunotherapy; Forkhead box protein 3; Peripheral blood mononuclear cell; Regulatory T cell; Macrophage inflammatory protein; Peanut; Immunopathology; Immunoglobulins; Treatment efficiency; Hypersensitivity; Cytokine; Oral administration; Immune regulation; Immunology; Interleukin 5; Treatment; Cell death; Immunotherapy; Immune tolerance; Interleukin 10; Groundnut; Apoptosis
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2009.05.022

Oral immunotherapy (OIT) has been thought to induce clinical desensitization to allergenic foods, but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported. The study objective was to investigate the clinical efficacy and immunologic changes associated with OIT. Children with peanut allergy underwent an OIT protocol including initial day escalation, buildup, and maintenance phases, and then oral food challenge. Clinical response and immunologic changes were evaluated. Of 29 subjects who completed the protocol, 27 ingested 3.9 g peanut protein during food challenge. Most symptoms noted during OIT resolved spontaneously or with antihistamines. By 6 months, titrated skin prick tests and activation of basophils significantly declined. Peanut-specific IgE decreased by 12 to 18 months, whereas IgG 4 increased significantly. Serum factors inhibited IgE–peanut complex formation in an IgE-facilitated allergen binding assay. Secretion of IL-10, IL-5, IFN-γ, and TNF-α from PBMCs increased over a period of 6 to 12 months. Peanut-specific forkhead box protein 3 T cells increased until 12 months and decreased thereafter. In addition, T-cell microarrays showed downregulation of genes in apoptotic pathways. Oral immunotherapy induces clinical desensitization to peanut, with significant longer-term humoral and cellular changes. Microarray data suggest a novel role for apoptosis in OIT.