Min Sook Ryu, Eun-Mi Yang, Young-Min Ye, Jae-Hyuk Jang, Junhwan Kim, Sae Young Lee, Hae-Sim Park
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引用次数: 0
Abstract
Purpose: Immunoglobulin E (IgE) induces mast cell/basophil activation by binding with FcεRIα and contributes to the development of allergic disease, in which targeting IgE has been considered an effective therapeutic strategy. YH35324 (YH) is a new hybrid protein with an extracellular domain consisting of FcεRIα, and its pharmacodynamic effect and safety were validated. This study aimed to evaluate the therapeutic potential of YH as an anti-IgE immunomodulator compared with omalizumab (Oma).
Methods: To evaluate the in vitro efficacy of YH in human mast cells, YH was treated with various methods, and the changes were confirmed through flow cytometry, immunoblot analysis, and immunocytochemistry. To evaluate the ex vivo efficacy of YH, the expression of FcεRIα on the surface of blood basophils was measured in 64 subjects with allergic diseases by flow cytometry. Serum soluble FcεRIα, CD23, and Mas-Related G-Protein Coupled Receptor Member X2 levels were measured by enzyme-linked immunosorbent assay.
Results: The YH-administered group exhibited significantly lower expression of FcεRIα on peripheral basophils compared to the Oma-administered group up to 14 days post-administration. YH directly suppressed FcεRIα expression on the surface of LAD2 cells, as it was bound to IgE-unbound FcεRIα and migrated into the cells by actin-dependent endocytosis, then was recycled by FcRn binding in the lysosome in vitro. Serum soluble FcεRIα levels were increased in the YH-administered group compared to the other groups and showed a positive correlation with serum-free IgE.
Conclusions: YH represents a new therapeutic agent for IgE-mediated allergic disease. Further studies are needed to evaluate its additional effects on the FcεRIα-mediated autoimmune mechanism.
期刊介绍：
The journal features cutting-edge original research, brief communications, and state-of-the-art reviews in the specialties of allergy, asthma, and immunology, including clinical and experimental studies and instructive case reports. Contemporary reviews summarize information on topics for researchers and physicians in the fields of allergy and immunology. As of January 2017, AAIR do not accept case reports. However, if it is a clinically important case, authors can submit it in the form of letter to the Editor. Editorials and letters to the Editor explore controversial issues and encourage further discussion among physicians dealing with allergy, immunology, pediatric respirology, and related medical fields. AAIR also features topics in practice and management and recent advances in equipment and techniques for clinicians concerned with clinical manifestations of allergies and pediatric respiratory diseases.
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