Nagao Mizuho, Hiraguchi Yukiko, Hosoki Koa, Tokuda Reiko, Usui Tomoko, Masuda Sawako, Yamaguchi Masao, Fujisawa Takao
Institute for Clinical Research, Mie National Hospital, Mie, Japan.
Int Arch Allergy Immunol. 2008;146 Suppl 1:47-53. doi: 10.1159/000126061. Epub 2008 May 27.
Rush immunotherapy (RIT) can confer rapid clinical benefit on patients with allergic rhinitis or asthma. However, biomarkers representing mechanisms for the efficacy of RIT are still to be established. CD203c is a basophil activation marker known to be upregulated by cross-linking of the FcepsilonRIalpha receptor and may serve as a useful marker.
We sought to investigate the changes in allergen-induced CD203c expression in patients with Japanese cedar pollen (JCP) pollinosis who received RIT.
Nine patients treated with RIT were enrolled in the study. Whole blood was incubated with various concentrations of JCP extract. CD203c expression on basophils was quantitated by means of flow cytometry. JCP-specific IgG4 levels in sera were measured with ELISA. Basophil histamine release, CAP-RAST to JCP (JCP-IgE) and total IgE were also examined. The biomarkers listed above were evaluated before and sequentially after RIT. Symptom and quality of life scores were obtained during pre- and posttreatment pollen seasons.
All patients showed significant improvement in symptom and quality of life scores after RIT. Serum JCP-specific IgG4 titers were significantly elevated at 1 month and remained at high levels 12 months after the treatment. Stimulation with JCP extract induced enhancement of basophil CD203c expression in a concentration-dependent manner except for 2 subjects in whom no increase in CD203c by an anti-IgE antibody was observed (nonresponders). Significant reductions in the responses were observed in 4 subjects after RIT (reduction in CD203c expression, RCE) whereas no changes were seen in 3 subjects (non-RCE). RCE subjects were older than non-RCE counterparts, with mean ages of 20 and 12 years, respectively. No significant changes in JCP-specific IgE and total IgE levels were seen before and after RIT.
Allergen-induced CD203c expression in basophils may represent, at least in part, the cellular mechanism for the therapeutic responses to RIT for JCP pollinosis. However, further larger-scale studies to confirm the utility of the test are necessary.
速发免疫疗法（RIT）可为过敏性鼻炎或哮喘患者带来快速的临床益处。然而，代表RIT疗效机制的生物标志物仍有待确定。CD203c是一种嗜碱性粒细胞活化标志物，已知通过FcεRIα受体的交联而上调，可能是一种有用的标志物。
我们试图研究接受RIT的日本雪松花粉（JCP）花粉症患者中变应原诱导的CD203c表达的变化。
9例接受RIT治疗的患者纳入研究。全血与不同浓度的JCP提取物孵育。通过流式细胞术定量嗜碱性粒细胞上的CD203c表达。用ELISA法检测血清中JCP特异性IgG4水平。还检测了嗜碱性粒细胞组胺释放、针对JCP的CAP-RAST（JCP-IgE）和总IgE。在RIT之前及之后依次评估上述生物标志物。在治疗前和治疗后的花粉季节获得症状和生活质量评分。
所有患者在RIT后症状和生活质量评分均有显著改善。血清JCP特异性IgG4滴度在治疗后1个月显著升高，并在12个月时维持在高水平。除2名未观察到抗IgE抗体使CD203c增加的受试者（无反应者）外，JCP提取物刺激以浓度依赖方式诱导嗜碱性粒细胞CD203c表达增强。4名受试者在RIT后反应显著降低（CD203c表达降低，RCE），而3名受试者未见变化（非RCE）。RCE受试者比非RCE受试者年龄大，平均年龄分别为20岁和12岁。RIT前后JCP特异性IgE和总IgE水平未见显著变化。
变应原诱导的嗜碱性粒细胞CD203c表达可能至少部分代表了JCP花粉症RIT治疗反应的细胞机制。然而，需要进一步的大规模研究来证实该检测的实用性。
