Role of Der p 1-specific B cells in immune tolerance during 2 years of house dust mite-specific immunotherapy
Role of Der p 1-specific B cells in immune tolerance during 2 years of house dust mite-specific immunotherapy
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DOI：
10.1016/j.jaci.2018.10.061
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发表时间：
2019-03-01
影响因子：
14.2
通讯作者：
Akdis, Mubeccel
中科院分区：
文献类型：
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作者：
Boonpiyathad, Tadech;van de Veen, Willem;Akdis, Mubeccel
背景：在过敏原特异性免疫治疗 (AIT) 过程中，对过敏原特异性 B 细胞在免疫球蛋白同种型表达、浆母细胞分化和调节性 B (Breg) 细胞发育方面的长期随访尚未见报道。目的：比较应答者和无应答患者在屋尘螨 AIT 2 年期间的过敏原特异性 B 细胞反应。方法：使用荧光染料标记的 Der p 1 特异性 B 细胞进行检测过敏原法。研究了产生 IgA、IgG(1) 和 IgG(4) 转换的 Der p 1 特异性 B 细胞、浆母细胞以及产生 IL-10 和 IL-1 受体拮抗剂 (IL-1RA) 的 Breg 细胞的频率，并将其与 AIT 的临床反应相关联。结果：25 名患者中有 16 名完成了为期 2 年的研究。 11 名有反应的患者对 AIT 表现出成功的反应，症状药物评分从 13.23 +/- 0.28 下降到 2.45 +/- 0.24 (P = 0.001)，皮肤点刺测试对屋尘螨的反应性从 7.0 +/- 1.3 下降到 2.7 +/- 0.5 mm (P < 5.001)。 AIT 后，IgG(4) 1 和 IgA 1 Der p 1 特异性 B 细胞显着增加，与 IgG(4) 1 部分无反应者相比，反应者中的频率显着更高，但 IgA 1 部分则不然。 2年后，与无反应者相比，反应者中浆母细胞和产生IL-10和/或IL-1RA的Breg细胞的频率更高。 Der p 1 特异性 IgG4 1 B 细胞、浆母细胞和 IL-10(+) 以及双阳性 IL-10 1 IL-1RA 1 Breg 细胞频率的增加与 AIT 过程中临床症状的改善显着相关。 IL-10(+) 和/或 IL-1RA 1 Breg 细胞。
Background: Long-term follow-up of allergen-specific B cells in terms of immunoglobulin isotype expression, plasmablast differentiation, and regulatory B (Breg) cell development during allergen-specific immunotherapy (AIT) has not been reported.Objective: Allergen-specific B-cell responses during 2 years of house dust mite AIT were compared between responder and nonresponder patients.Methods: B cells specific for Der p 1 were detected by using the fluorochrome-labeled allergen method. The frequencyof IgA-, IgG(1)-and IgG(4)-switchedDer p 1-specificBcells, plasmablasts, and IL-10- and IL-1 receptor antagonist (IL-1RA)-producing Breg cells were investigated and correlated to clinical response to AIT.Results: Sixteen of 25 patients completed the 2-year study. Eleven responder patients showed a successful response to AIT, as measured by a decrease in symptom-medication scores from 13.23 +/- 0.28 to 2.45 +/- 0.24 (P = .001) and a decrease in skin prick test reactivity to house dust mite from 7.0 +/- 1.3 to 2.7 +/- 0.5 mm (P 5.001). IgG(4) 1 and IgA 1 Der p 1-specific B cells showed a significant increase after AIT, with a significantly greater frequency in responders compared with nonresponders in the IgG(4) 1 but not the IgA 1 fraction. The frequency of plasmablasts and IL-10- and/or IL-1RA-producing Breg cells was greater among responders compared with nonresponders after 2 years. The increased frequency of Der p 1-specific IgG4 1 B cells, plasmablasts, and IL-10(+) and dual-positive IL-10 1 IL-1RA 1 Breg cells significantly correlated with improved clinical symptoms over the course of AIT.Conclusion: Allergen-specific B cells in patients responding to AIT are characterized by increased numbers of IgA- and IgG(4)-expressing Der p 1-specific B cells, plasmablasts, and IL-10(+) and/or IL-1RA 1 Breg cells.