Differential response in allergen‐specific IgE, IgGs, and IgA levels for predicting outcome of oral immunotherapy

Abstract

Background: Oral immunotherapy (OIT) induces desensitization and/or tolerance in patients with persistent food allergy, but the biomarkers of clinical outcomes remain obscure. Although OIT-induced changes in serum allergen-specific IgE and IgG4 levels have been investigated, the response of other allergen-specific IgG subclasses and IgA during OIT remains obscure. Methods: A pilot study was conducted to investigate egg OIT-induced changes in allergen-specific IgE, IgG subclasses, and IgA levels and search for possible prediction biomarkers of desensitization. We measured serum levels of egg white-, ovomucoid-, and ovalbumin-specific IgE, IgA, and IgG subclasses by high-sensitivity allergen microarray in 26 children with egg allergy who received rush OIT. Results: Allergen-specific IgE gradually decreased while IgG4 increased during 12-month OIT. Serum levels of IgG1, IgG3, and IgA increased significantly after the rush phase, then decreased during the maintenance phase. IgG2 levels changed in a manner similar to that of IgG4. In particular, significantly high fold increases in egg whitespecific IgG1, relative to baseline, after the rush phase and high IgA levels before OIT were observed in responders, compared with low-responders to OIT. Patients who could not keep desensitization showed relatively small changes in all immunoglobulin levels during OIT. Conclusion: The response to OIT was associated with significant increases in serum allergen-specific IgG1 levels after rush phase and high baseline IgA levels, compared with small changes in immunoglobulin response in low-responders. The characteristic IgG1 changes and IgA levels in the responders could be potentially useful biomarkers for the prediction of positive clinical response to OIT.

Food allergy: immune mechanisms, diagnosis and immunotherapy

“…Other changes observed over the course of OIT include those in allergen-specific IgE levels, which decrease, whereas allergen-specific IgG4 levels increase 86 . Although levels of all IgG subclasses rise during OIT and may contribute differentially to the suppression of IgE-mediated responses through binding FcγRIIb, the increase in the ratio of IgG4 to IgE is particularly notable, and IgG4 has become an important research focus 87 .…”

“…Initially during desensitization, mast cell and basophil activation are decreased through an unclear mechanism, and a shift occurs from the predominance of T helper 2 (T H 2) cells 177 to that of allergen-specific T reg cells 77 , which in turn may lead to the observed shift in allergen-specific antibodies from the IgE to the IgG4 isotype 86,178 . As has been proposed in immunotherapy for venom allergies, IgG4 antibodies may compete with IgE antibodies for food allergens, further dampening the T H 2 cell-mediated immune response 179,180 .…”

Deciphering the black box of food allergy mechanisms

“…Current data support an initial increase in IgE followed by an eventual decrease in IgE with OIT. 36,47,48 The mechanism behind a shift from IgE to IgG4 is unclear and may likely involve anergy or deletion of IgE-producing B cells or increases in IgG4-producing B cells.…”

Oral immunotherapy for food allergy

“…In healthy individuals, Ag-specific CD4 + Treg and type 1 regulatory T cells (Tr1) secrete IL-10, which suppresses IgE production while inducing that of IgG 4 [56]; in OIT, Ag-specific IgE decreases while IgG 4 increases [57]. Studies of Ag-specific immunotherapy for the major bee venom Ag, phospholipase A 2 , suggest that Ag-specific type 1 B regulatory cells (Breg) increasingly produce IL-10 over the course of immunotherapy, contributing to IgG 4 production [58,59] and inhibiting IgE-dependent mast cell activation [60].…”