暂无摘要。

Objective: To investigate the effects of subcutaneous immunotherapy (SCIT) on patients\' immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers. Methods: A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results: After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT:Z=-2.298, P<0.05; DM-SCIT:Z=-3.411, P<0.001); total ACT score (SM-SCIT:Z=-2.054, P<0.05; DM-SCIT:Z=-2.014, P<0.05) and total medication scores (SM-SCIT:Z=-3.799, P<0.000 1; DM-SCIT:Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group (t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group (P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated (Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions(Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions (Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment (Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment (Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 (r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 (r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion: Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.
目的： 探讨过敏原皮下特异性免疫治疗（subcutaneous immunotherapy，SCIT）在治疗早期对患者免疫指标和代谢水平的影响，深入了解SCIT治疗在调节免疫反应和代谢水平方面的作用，为进一步发现潜在生物标志物提供参考数据。 方法： 采用纵向研究方法，纳入2017年11月至2022年2月期间于广州医科大学附属第一医院儿科接受尘螨过敏原SCIT的受试者40例，其中单螨制剂治疗（single mite subcutaneous immunotherapy，SM-SCIT）和双螨制剂（double mite subcutaneous immunotherapy，DM-SCIT）治疗受试者各20例。本研究检测了受试者治疗前和治疗12个月后的尘螨过敏原特异性抗体和多元不饱和脂肪酸代谢水平，同时进行了肺功能检查，并通过症状视觉模拟量表（visual analogue scale，VAS）、哮喘控制测试问卷（asthma control test，ACT）和用药总评分（total medication scores，TMS）对患者的疗效进行随访，采用t检验、Mann-Whitney U检验等方法进行结果统计分析。 结果： 经SCIT治疗12个月后，两组的VAS总分（SM-SCIT：Z=-2.298，P<0.05；DM-SCIT：Z=-3.411，P<0.001）显著下降；ACT总分（SM-SCIT：Z=-2.054，P<0.05；DM-SCIT：Z=-2.014，P<0.05）和总用药评分（SM-SCIT：Z=-3.799，P<0.000 1；DM-SCIT：Z=-3.474，P<0.001）显著升高，此外，双螨治疗组MMEF75/25值显著升高（t=-2.253，P<0.05）。单螨治疗组的sIgE无明显变化（P>0.05），Der p、Der f、p 1、p 2、f 2和p 21组分sIgG4水平均显著升高（Z分别为-2.651、-3.771、-2.949、-2.912、-2.725、-2.128、-3.285，P均<0.05）；双螨治疗组的 Der p 2、f 2、p 7和p 23 组分sIgE（Z分别为-1.965、-2.028、-2.406、-2.134，P均<0.05）和Der p、Der f、p 1、p 2、f 1、f 2、p 10、p 21和p 23组分sIgG4水平均显著升高（Z分别为-3.808、-3.845、-3.061、-2.688、-2.464、-3.211、-2.371、-2.091、-2.427，P均<0.05）。代谢组学分析显示，在治疗初期，SM-SCIT治疗后花生四烯酸、二十二碳六烯酸、二十二碳五烯酸、二十碳五烯酸、5，9，12-十八碳三烯酸、5（S）-羟化二十烷四烯酸、二高-γ-亚麻酸显著升高（Z分别为-2.191、-2.497、-1.988、-2.090、-2.19、-2.803、-2.073，P均<0.05）；DM-SCIT组治疗后5（S）-羟化二十烷四烯酸显示升高，α-亚麻酸、二十碳二烯酸、二十碳一烯酸显著下降（Z分别-1.988、-2.090、-2.497、-1.988，P均<0.05）。相关性分析表明，花生四烯酸与尘螨特异性IgG4的变化呈显著负相关（r=-0.499，P<0.05），α-亚麻酸、5，9，12-十八碳三烯酸、二十碳五烯酸与尘螨der p 2的ΔsIgG4（r分别为0.451、0.420、0.474，P均<0.05）呈正相关。 结论： SCIT期间过敏原特异性抗体水平和多不饱和脂肪酸代谢水平发生显著变化，并且两者之间可能相互影响、相互作用。.

Objective: To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and compliance. Method: Use a retrospective real-world study, clinical data from 156 children aged 5-16 years who received subcutaneous immunotherapy (SCIT) with double mite allergen preparation in the pediatrics department of the Third Affiliated Hospital of Sun Yat sen University from June 2019 to September 2020 were selected for allergic rhinitis (AR) and/or allergic asthma (bronchial asthma, BA), including gender, age, total VAS(visual analogue scale) score and CSMS(combined symptom and medication scores) score at different time points (before treatment, 4-6 months, 1 year, and 2 years after initiation of desensitization), peripheral blood eosinophil counts (EOS), serum total IgE (tIgE), specific IgE (tIgE), and serum IgE (tIgE), specific IgE (sIgE), tIgG4, and incidence of local and systemic adverse reactions. All patients had a consistent regimen during the initial treatment phase (dose-escalation phase), which was performed as directed. Among them, 81 cases (observation group) continued to continue subcutaneous injection of 1 ml of vial No. 3 every 4-6 weeks during the dose maintenance phase, while 75 cases (control group) followed the old traditional regimen during the maintenance phase (i.e., change to a new vial to halve the amount of vial No. 3 by 0.5 ml, and then 0.75 ml after 1-2 weeks, and 1 ml in a further interval of 1-2 weeks). The clinical efficacy, safety and adherence to the treatment were compared between the two groups. Results: A total of 81 cases of 156 children were included in the observation group, of which 58 children with AR, 15 children with BA, and 8 children with AR combined with BA; 75 cases were included in the conventional control group, of which 52 children with AR, 16 children with BA, and 7 children with AR combined with BA. In terms of safety, the difference in the incidence of local and systemic adverse reactions between the two groups was not statistically significant (χ2=1.541 for local adverse reactions in the control group, χ2=0.718 for the observation group; χ2=0.483 for systemic adverse reactions in the control group, χ2=0.179 for the observation group, P value >0.05 for all of these), and there were no grade Ⅱ or higher systemic adverse reactions in any of them. In the control group, there were 15 cases of dropout at 2 years of follow-up, with a dropout rate of 20.0%; in the observation group, there were 7 cases of dropout at 2 years of follow-up, with a dropout rate of 8.6%, and there was a statistically significant difference in the dropout rates of the patients in the two groups (χ2=4.147, P<0.05). Comparison of serological indexes and efficacy (compared with baseline at 3 different time points after treatment, i.e., 4-6 months, 1 year and 2 years after treatment), CSMS scores of the observation group and the conventional control group at 4-6 months, 1 year and 2 years after treatment were significantly decreased compared with the baseline status (t-values of the conventional group were 13.783, 20.086 and 20.384, respectively, all P-values <0.001, and t-values of the observation group were 15.480, 27.087, 28.938, all P-values <0.001), and VAS scores also decreased significantly from baseline status in both groups at 4-6 months, 1 year, and 2 years of treatment (t-values of 14.008, 17.963, and 27.512 in the conventional control group, respectively, with all P-values <0.001, and t-values of 9.436, 13.184, and 22.377 in the observation group, respectively; all P-values <0.001). Intergroup comparisons showed no statistically significant differences in CSMS at baseline status, 4-6 months, 1 year and 2 years (t-values 0.621, 0.473, 1.825, and 0.342, respectively, and P-values 0.536, 0.637, 0.070, and 0.733, respectively), and VAS was no statistically significant difference in comparison between groups at different time points (t-values of 1.663, 0.095, 0.305, 0.951, P-values of 0.099, 0.925, 0.761, 0.343, respectively); suggesting that the treatment regimens of the observation group and the conventional control group were clinically effective, and that the two regimens were comparable in terms of efficacy. The peripheral blood eosinophil counts of the observation group and the conventional control group decreased significantly from the baseline status at 4-6 months, 1 year and 2 years of treatment (t-values of the conventional group were 3.453, 5.469, 6.273, P-values <0.05, and the t-values of the observation group were 2.900, 4.575, 5.988, P-values <0.05, respectively). 4-6 months, 1 year and 2 years compared with the baseline status tIgE showed a trend of increasing and then decreasing (t-value in the conventional group was -5.328, -4.254, -0.690, P-value was 0.000, 0.000, 0.492, respectively, and t-value in the observation group was -6.087, -5.087, -0.324, P-value was 0.000, 0.000, 0.745, respectively). However, the results of intergroup comparisons showed no statistically significant differences in serological indices and efficacy between the two groups in terms of peripheral blood eosinophil counts at baseline status, 4-6 months, 1 year and 2 years (t-values of 0.723, 1.553, 0.766, and 0.234, respectively; P-values of 0.471, 0.122, 0.445, and 0.815, respectively), tIgE (t-values of 0.170, -0.166, -0.449, 0.839, P-values 0.865, 0.868, 0.654, 0.403, respectively), tIgG4 (t-values 1.507, 1.467, -0.337, 0.804, P-values 0.134, 0.145, 0.737, 0.422, respectively). Conclusion: Both immunotherapy regimens for airway allergic diseases with double mite allergen subcutaneous immunotherapy have significant clinical efficacy, low incidence of adverse reactions, and the observation group has better patient compliance than the control group.
目的： 探讨儿童气道过敏性疾病标准化螨变应原免疫治疗的优化方案，观察其临床疗效、安全性和依从性。 方法： 采用回顾性真实世界研究，选取2019年6月至2020年9月在中山大学附属第三医院儿科接受双螨变应原制剂皮下免疫治疗（Subcutaneous immunotherapy，SCIT）的变应性鼻炎（allergic rhinitis，AR）和（或）过敏性哮喘（支气管哮喘，bronchial asthma，BA）的5~16岁共156例患儿的临床资料，包括性别、年龄、不同时间节点（治疗前，启动脱敏治疗后4~6个月、1年、2年时）总VAS（视觉模拟量表）评分和CSMS（综合症状和用药评分）评分、外周血中嗜酸性粒细胞计数（EOS）、血清总IgE（tIgE）、特异性IgE（sIgE）、tIgG4、局部及全身不良反应发生率。所有患者在初始治疗阶段（剂量递增阶段）的方案一致，均按说明书进行。其中，81例（观察组）在剂量维持阶段持续继续每4~6周皮下注射1次，每次注射3号瓶1 ml；75例（对照组）维持阶段按照旧的传统方案进行（即换新瓶减半量3号瓶0.5 ml，1~2周后0.75 ml，再间隔1~2周1 ml）。比较两组患者治疗的临床疗效、安全性及依从性。 结果： 156例患儿中观察组共纳入81例，其中AR患儿有58例，BA患儿15例，AR合并BA患儿有8例；常规对照组共纳入75例，AR患儿有52例，BA患儿16例，AR合并BA患儿有7例。在安全性方面，两组患者的局部和全身不良反应发生率差异均无统计学意义（局部不良反应对照组χ2=1.541，观察组χ2=0.718；全身不良反应对照组χ2=0.483，观察组χ2=0.179，P值均>0.05），且均无Ⅱ级以上全身不良反应发生。对照组随访2年脱漏15例，脱落率20.0%；观察组随访2年脱漏7例，脱落率8.6%，两组患者脱落率差异有统计学意义（χ2=4.147，P<0.05）。血清学指标及疗效对比（在治疗后3个不同的时间节点即治疗4~6个月、1年及2年时与基线进行比较），观察组和常规对照组治疗4~6个月、1年及2年时CSMS评分较基线状态明显下降（常规组t值分别为13.783，20.086，20.384，P值均<0.001；观察组t值分别为15.480，27.087，28.938，P值均<0.001）；两组患者治疗4~6个月、1年及2年时VAS评分也均较基线状态明显下降（常规组t值分别为14.008，17.963，27.512，P值均<0.001；观察组t值分别为9.436，13.184，22.377，P值均<0.001）；组间比较结果显示，基线状态、4~6个月、1年及2年时CSMS差异无统计学意义（t值分别为0.621，0.473，1.825，0.342；P值分别为0.536，0.637，0.070，0.733），VAS在不同时间点的组间比较差异也无统计学意义（t值分别为1.663，0.095，0.305，0.951；P值分别为0.099，0.925，0.761，0.343）；提示观察组和常规对照组的治疗方案均临床显效，且两种方案疗效相当。观察组和常规对照组治疗4~6个月、1年及2年时外周血嗜酸性粒细胞计数均较基线状态明显下降（常规组t值分别为3.453，5.469，6.273，P值均<0.05；观察组t值分别为2.900，4.575，5.988，P值均<0.05），两组患者在治疗4~6个月、1年及2年时较基线状态tIgE呈现先升高后降低的趋势（常规组t值分别为-5.328，-4.254，-0.690，P值分别为0.000，0.000，0.492；观察组t值分别为-6.087，-5.087，-0.324，P值分别为0.000，0.000，0.745）。但组间比较结果显示血清学指标及疗效在基线状态、4~6个月、1年及2年时外周血嗜酸性粒细胞计数在两组之间无明显统计学差异（t值分别为0.723，1.553，0.766，0.234；P值分别为0.471，0.122，0.445，0.815），tIgE（t值分别为0.170，-0.166，-0.449，0.839；P值分别为0.865，0.868，0.654，0.403），tIgG4（t值分别为1.507，1.467，-0.337，0.804；P值分别为0.134，0.145，0.737，0.422）。 结论： 针对气道过敏性疾病双螨变应原皮下免疫治疗的两种免疫治疗方案均有显著的临床疗效，不良反应发生率低，观察组较对照组患者依从性更好。.

The prevalence of food allergy is increasing worldwide and seriously affects the living quality of patients and their families. Egg allergy is one of the commonest forms of food allergy. The traditional regimen is to delay the introduction of eggs to infant complementary foods, which is not able to reduce the prevalence of egg allergies and causes negative effects on infants\' physical and psychological conditions. Oral tolerance therapy is an approach to establish immune tolerance by the active suppression of specific immune responses to antigens in the gastrointestinal tract. The development of oral tolerance through early introduction of eggs to infant complementary has proven effective in randomized controlled trials, which has been incorporated into infant feeding guidelines in many countries. This article focuses on the mechanism, efficacy and safety of oral tolerance induction in the prevention of egg allergy.
食物过敏的患病率逐年升高，严重影响了患者及其家庭的生活质量。其中鸡蛋是主要过敏原的一种，传统的预防鸡蛋过敏的方法是延迟在婴儿辅食中添加鸡蛋，但这种方法并不能降低鸡蛋过敏的患病率，反而可能会影响婴儿的身心健康。口服耐受疗法是通过主动抑制胃肠道对于抗原的特异性反应而建立免疫耐受的过程。目前多项研究表明通过早期引入鸡蛋诱导口服耐受可以预防鸡蛋过敏，并已被纳入许多国家的婴儿喂养指南。本文在此主要阐述口服耐受诱导疗法在预防鸡蛋过敏中的机制、疗效及安全性。.

Allergies play a pivotal role in the daily practice of ENT specialists. Allergic symptoms induced by inhalant allergens are widespread in the population and can manifest through a wide range of symptoms, including rhinorrhea, sneezing, conjunctival redness, cough and dyspnea. Inconsistent diagnosis and treatment of allergic conditions can lead to reduced quality of life, decreased work performance, and socioeconomically significant secondary diseases. In addition to the medical history, the skin prick test and serological IgE diagnostics are the most important diagnostic procedure for detecting type-I allergies. To clarify clinical relevance, molecular diagnostics and nasal provocation testing may be employed. The key to effective treatment lies in a comprehensive allergological diagnosis coupled with a detailed patient history. General treatment recommendations such as allergen avoidance and nasal irrigation should complement pharmacological therapy. In the treatment of allergic rhinitis topical steroids are first line treatment options. The primary goal of treatment is symptom control, and if control is insufficient, causal therapy through specific allergen immunotherapy is recommended. Challenges in the ENT clinic involve selecting the necessary diagnostics and appropriate, effective treatments. Hence, using diagnostic and treatment algorithms, as well as standardized patient history questionnaires, can serve as invaluable tools in daily patient interactions, especially considering limited time availability.

Art v4.01 is a well-known profilin protein belonging to the pan-allergens group and is commonly involved in triggering allergic asthma, polyallergy, and cross-sensitization. It is also referred to as Wormwood due to its origin. Crude wormwood extracts are applied for allergen-specific immunotherapy (AIT). Whether the recombinant Art v4.01 (rArt v4.01) can produce in vivo immunological tolerance by subcutaneous immunotherapy (SCIT) remains elusive. In this study, to investigate the in vivo immunological response of rArt v4.01, Th2, Th1, Treg, Th17 type-related cytokines and phenotypes of immune cells were tested, facilitating the exploration of the underlying mechanisms. The expression and purification of Art v4.01 were carried out using recombinant techniques. Allergic asthma female BALB/c mice were induced by subcutaneous sensitization of wormwood pollen extract and intranasal challenges. SCIT without adjuvant was performed using the rArt v4.01 and wormwood pollen extract for 2 weeks. Following exposure to challenges, the levels of immunoglobulin E (IgE), cytokines, and inflammatory cells were assessed through enzyme-linked immunosorbent assay (ELISA) and histological examination of sera, bronchoalveolar lavage fluid (BALF), and lung tissue. These parameters were subsequently compared between treatment groups receiving rArt v4.01 and wormwood pollen extract. The rArt v4.01 protein was expressed, which had a high purity (>90%) and an allergenic potency. Compared with the pollen extract, rArt v4.01 was superior in terms of reducing the number of white blood cells (WBCs), total nucleated cells (TNCs), and monocytes (MNs) in BALF and the degree of lung inflammation (1.77±0.99 vs. 2.31±0.80, P > 0.05). Compared with the model group, only rArt v4.01 reduced serum IgE level (1.19±0.25 vs. 1.61±0.17 μg/ml, P = 0.062), as well as the levels of Th2 type-related cytokines (interleukin-4 (IL-4) (107.18±16.17 vs. 132.47±20.85 pg/ml, P < 0.05) and IL-2 (19.52±1.19 vs. 24.02±2.14 pg/ml, P < 0.05)). The study suggested that rArt v4.01 was superior to pollen extract in reducing the number of inflammatory cells in BALF, pneumonitis, levels of pro-inflammatory cytokines, and serum IgE level. These findings confirmed that Art v4.01 could be a potential candidate protein for allergen-specific immunotherapy.

Autoantigen-specific immunotherapy using peptides offers a more targeted approach to treat autoimmune diseases, but clinical implementation has been challenging. We previously showed that multivalent delivery of peptides as soluble antigen arrays (SAgAs) efficiently protects against spontaneous autoimmune diabetes in the non-obese diabetic (NOD) mouse model. Here, we compared the efficacy, safety, and mechanisms of action of SAgAs versus free peptides. SAgAs, but not their corresponding free peptides at equivalent doses, efficiently prevented the development of diabetes. SAgAs increased the frequency of regulatory T cells among peptide-specific T cells or induce their anergy/exhaustion or deletion, depending on the type of SAgA used (hydrolysable (hSAgA) and non-hydrolysable \'click\' SAgA (cSAgA)) and duration of treatment, whereas their corresponding free peptides induced a more effector phenotype following delayed clonal expansion. Over time, the peptides induced an IgE-independent anaphylactic reaction, the incidence of which was significantly delayed when peptides were in SAgA form rather than in free form. Moreover, the N-terminal modification of peptides with aminooxy or alkyne linkers, which was needed for grafting onto hyaluronic acid to make hSAgA or cSAgA variants, respectively, influenced their stimulatory potency and safety, with alkyne-functionalized peptides being more potent and less anaphylactogenic than aminooxy-functionalized peptides. Immunologic anaphylaxis occurred in NOD mice in a dose-dependent manner but not in C57BL/6 or BALB/c mice; however, its incidence did not correlate with the level of anti-peptide antibodies. We provide evidence that SAgAs significantly improve the efficacy of peptides to induce tolerance and prevent autoimmune diabetes while at the same time reducing their anaphylactogenic potential.

OBJECTIVE: To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma.
METHODS: In a prospective randomized controlled study, 98 children with dust mite-induced allergic asthma were randomly divided into a control group (n=49) and an SCIT group (n=49). The control group received inhaled corticosteroid treatment, while the SCIT group additionally received a standardized three-year SCIT regimen. The two groups were compared based on peripheral blood eosinophil percentage, visual analogue score (VAS), total medication score, Asthma Control Test/Childhood Asthma Control Test scores, fractional exhaled nitric oxide (FeNO), and lung function before treatment, and at 6 months, 1 year, 2 years, and 3 years after treatment. Adverse reactions were recorded post-injection to evaluate the safety of SCIT.
RESULTS: Compared with pre-treatment levels, the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils, VAS, total medication score, and FeNO, while lung function significantly improved, and asthma control levels were better 3 years after treatment (P<0.05). Compared with the control group, the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment (P<0.05). A total of 2 744 injections were administered, resulting in 157 cases (5.72%) of local adverse reactions and 4 cases (0.15%) of systemic adverse reactions, with no severe systemic adverse events.
CONCLUSIONS: SCIT is an effective and safe treatment for allergic asthma in children.
目的: 探讨尘螨皮下免疫治疗（subcutaneous immunotherapy, SCIT）应用于儿童过敏性哮喘的疗效和安全性。方法: 采用前瞻性随机对照研究，将98例尘螨过敏哮喘患儿按随机数字表法分为对照组和SCIT组，每组49例。对照组吸入激素治疗；SCIT组除吸入激素治疗外，加用3年标准化SCIT。比较两组治疗前、治疗后6个月、治疗后1年、治疗后2年、治疗后3年外周血嗜酸性粒细胞百分比、视觉模拟评分、总用药评分、哮喘控制测试评分/儿童哮喘控制测试评分、呼出气一氧化氮和肺功能的差异。记录注射后不良反应，评估SCIT的安全性。结果: 与治疗前相比，SCIT组3年后外周血嗜酸性粒细胞百分比、视觉模拟评分、总用药评分和呼出气一氧化氮显著下降，肺功能显著改善，哮喘控制水平更佳（P<0.05）；与对照组相比，SCIT组3年后各评估指标改善较对照组更明显（P<0.05）。共完成2 744次注射，发生局部不良反应157次（5.72%），全身不良反应4次（0.15%），无严重全身不良反应发生。结论: SCIT是一种有效、安全的儿童过敏性哮喘治疗方法。.

UNASSIGNED: Allergen-specific immunotherapy (AIT) is able to restore immune tolerance to allergens in allergic patients. However, some patients do not or only poorly respond to current treatment protocols. Therefore, there is a need for deeper mechanistic insights and further improvement of treatment strategies. The relevance of the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, has been investigated in several inflammatory diseases, including allergic asthma. However, its potential role in AIT still needs to be addressed.
UNASSIGNED: A murine model of AIT in ovalbumin-induced allergic airway inflammation was performed in AhR-deficient (AhR-/-) and wild-type mice. Furthermore, AIT was combined with the application of the high-affinity AhR agonist 10-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (10-Cl-BBQ) as an adjuvant to investigate the effects of AhR activation on therapeutic outcome.
UNASSIGNED: Although AhR-/- mice suffer stronger allergic responses than wild-type mice, experimental AIT is comparably effective in both. Nevertheless, combining AIT with the administration of 10-Cl-BBQ improved therapeutic effects by an AhR-dependent mechanism, resulting in decreased cell counts in the bronchoalveolar fluid, decreased pulmonary Th2 and Th17 cell levels, and lower sIgE levels.
UNASSIGNED: This study demonstrates that the success of AIT is not dependent on the AhR. However, targeting the AhR during AIT can help to dampen inflammation and improve tolerogenic vaccination. Therefore, AhR ligands might represent promising candidates as immunomodulators to enhance the efficacy of AIT.

BACKGROUND: Milk oral immunotherapy is the riskiest and most unpredictable form of oral immunotherapy. We aimed to produce a low allergenic product than conventional once baked-cake/muffin, to develop indirect in-house ELISA to check the tolerance status with milk products and evaluate IgE reactivity of patients\' sera via western blotting (WB) and indirect in-house ELISA.
METHODS: A low allergenic product named biscotti-twice baked-cake was developed, and the total protein concentration was determined. The protein content was studied by SDS-PAGE and proteomics. Milk-specific IgE (sIgE) binding assays were performed by WB and indirect in-house ELISA by using patients\' sera.
RESULTS: Casein band intensity was observed to be lower in the biscotti-twice baked-cake than in the once baked-cake (p = .014). Proteomics analysis and αS1-casein measurement showed that the lowest intensity of casein was found in biscotti. The low binding capacity of milk sIgE to biscotti compared with once baked-cake was shown by WB (p = .0012) and by indirect in-house ELISA (p = .0001). In the ROC analysis, the area under the curve (AUC) of the in-house ELISA IgE was comparable with Uni-CAP milk and casein sIgE. The AUC of the in-house ELISA IgE for cake (0.96) and biscotti (1) was slightly better than Uni-CAP milk sIgE (0.94; 0.97) and casein sIgE (0.96; 0.97), respectively.
CONCLUSIONS: The low allergenicity of the newly developed low allergenic product \"biscotti-twice baked-cake\" has been demonstrated by in vitro experiments. Biscotti could be a safe treatment option than once baked-cake/muffin in patients who are reactive to once baked-milk products.