음식물 알러지 치료를 위한 새로운 IgE 차단제와 Bifidobacterium longum 병용 치료에 대한 연구

Abstract

Food allergy (FA) is a hypersensitive immune reaction to non-pathogenic food with rapidly growing global occurrence. Although oral immunotherapy (OIT) is the most effective treatment for FA to date, adverse responses are common and can be severe during OIT. Immunoglobulin E (IgE)-mediated FA is the most common and anti-IgE treatment omalizumab can be used for FA. However, omalizumab is an IgG1 antibody and may cause IgG-mediated severe anaphylaxis by forming an allergen-IgE-omalizumab immune complex. In addition, the efficacy of omalizumab depends on the patient’s serum IgE level and body weight. Therefore, more effective and safer anti-IgE therapy alternatives are needed. Additionally, probiotics have been suggested as a promising approach to treat FAs. However, the probiotic therapy is limited in the therapeutic efficacy alone and needed add-on therapy. I sought to examine whether IgETRAP could enhance the therapeutic efficacy of probiotics, Bifidobacterium longum (B. longum), in ovalbumin (OVA)- and peanut-induced mouse FA model. I designed IgETRAP by linking the FcεRIα extracellular domain to a human IgD/IgG4 hybrid Fc domain. In vitro binding affinity, receptor dissociation, and blocking effect of IgETRAP for human IgE were examined using a surface plasmon resonance assay, biolayer interferometry assay, and inhibiting mast cell degranulation, respectively. Blocking efficacy of free IgE was also analyzed using IgETRAP compared with omalizumab in cynomolgus monkeys. Then, the combination therapy of B. longum with IgETRAP was assessed in an OVA- and peanut-induced mouse FA models. IgETRAP was superior to the omalizumab in terms of IgE binding affinity, receptor dissociation function, and the suppression of mast cell degranulation. Additionally, administration of IgETRAP significantly reduced the level of free IgE in monkey serum even compared with omalizumab. Most importantly, IgETRAP, in combination with B. longum, substantially decreased intestinal mast cells, as well as the serum levels of free IgE and MCPT-1, to a greater degree than either alone, leading to alleviation of allergy symptoms. Collectively, these findings indicate that IgETRAP is an effective IgE blocker and the combination of B. longum with IgETRAP could present a clinically applicable novel therapeutic regimen for FAs.