变应性鼻炎免疫治疗的研究进展

变应性鼻炎是一种由变应原激发并通过Ig E介导的鼻黏膜炎性疾病,因其反复发作的鼻部症状和并发症,给临床治疗带来很大挑战。免疫治疗是目前唯一能够改变变应性鼻炎自然病程、针对病因的治疗方法。近来,包括新的给药途径、变应原改造在内的各种新型免疫治疗方法大量涌现,给变应性鼻炎治疗提供更多有效和安全的选择。本文针对变应性鼻炎免疫治疗的最新研究进展进行综述,并对未来的方向进行展望。     

变应性鼻炎伴哮喘患者特异性免疫治疗速发型不良反应的观察

本文回顾性分析了我院2009年1月至2015年7月接受屋尘螨变应原疫苗皮下注射特异性免疫治疗113例过敏性鼻炎伴哮喘患者,观察其不良反应发生情况。结果显示113例患者中,90人(79.65%)发生速发型局部一般不良反应1491次(33.83%);57人(50.44%)发生速发型局部严重反应(local large reactions,LLR)242次(5.49%);13人(11.50%)发生速发型全身不良反应22次(0.50%),其中Ⅰ级16次(0.36%),Ⅱ级5次(0.11%),Ⅲ级1次(0.02%),无Ⅳ级不良反应发生;速发型局部不良反应随注射浓度的升高而增多,以儿童组发生率最高,但男女总体无差异;速发型全身不良反应以剂量快速上升组最高,女性全身性不良反应率高于男性(以针次计算,P0.01),但各个年龄段无差异;部分患者速发型LLR后可能发生速发型全身不良反应。提示屋尘螨特异性免疫治疗严重不良反应发生率较低,大多数不良反应集中在剂量快速上升阶段和维持阶段,部分患者LLR可能提示全身不良反应的发生,对于年龄≤14岁儿童患者应及时调整注射剂量预防速发型LLR的发生。     

脱敏疗法治疗常年性变应性鼻炎的疗效观察

本文对76例常年性变应性鼻炎患者,分二组进行脱敏治疗,甲组用粉尘螨注射液,乙组用吸入物抗原。甲、乙两组在治疗前及治疗半年后记分别测定血清IgG、IgE。结果表明,甲、乙两组治疗前后记分比较均有非常显著性差异(P均<0.01)。两组间有效率无显著性差异(P>0.05)。两组在治疗前后血清IgG均有非常显著差异(P<0.01)。血清IgE也有显著差异(P<0.05)。血清IgG上升与IgE下降与临床症状好转相一致。甲组具有治疗方便,疗程短等优点。     

舌下免疫治疗变应性鼻炎疗效预测生物标志物研究进展

变应性鼻炎（AR）是IgE介导的鼻黏膜的Ⅰ型变态反应。变应原特异性免疫治疗（AIT）不仅可以有效地、长效地控制鼻部症状,并且可以改变疾病自然进程。由于部分患者对免疫治疗反应不佳,且疗程较长,确定可以预测和评估疗效的生物学指标则尤为关键。本文综述了舌下免疫治疗（SLIT）AR的疗效预测和评估的生物学标志物的研究进展。多种免疫细胞、免疫球蛋白、细胞因子的变化与SLIT的疗效相关,被认为是候选生物标志物,但其有效性、相关度还有待进一步验证。     

变应性鼻炎特异性免疫治疗患者的依从性及相关因素分析

目的研究变应性鼻炎特异性免疫治疗患者的依从性及其影响因素。方法对过去3年接受特异性免疫治疗的变应性鼻炎患者进行回顾性调查，对未完成基础疗程的患者采取电话方式了解其不依从的原因，率的比较采用χ^2检验进行分析。结果特异性免疫治疗患者的完全依从率为70．1％；儿童的完全依从率为84．6％，高于成人（64．16％，58．46％），有统计学意义（χ^2值分别为8．712，6．441，P〈0．05）；不依从的原因调查表明，效果不明显或无效占29．49％，工作忙或学业紧张占20．86％，症状消失或好转占12．23％。结论变应性鼻炎特异性免疫治疗患者的依从性不甚理想，其中儿童的依从性高于成人。调查结果提示治疗中应有针对性地采取相应的干预措施，以提高患者免疫治疗的依从率，从而提高疗效。     

变应性鼻炎患者经特异性免疫治疗后体内IL-4、IFN-γ、SIgE的变化

随着对变应性鼻炎(AR)分子生物学和免疫学研究的日益重视，人们对AR有了更深刻的认识。但对AR特异性免疫治疗前、后IL-4、IFN-γ、SIgE的变化情况尚未见报道。我们自2001年1月至2024年3月对只有尘螨过敏的22例AR患者进行了特异性免疫治疗前、后血清和鼻灌洗液中IL-4、IFN-γ、SIgE、TIgE的测定并进行了比较分析及临床意义的探讨。     

变应性鼻炎患者免疫治疗前后IL-5、ECP的动态观察

在变应性鼻炎(AR)的发病过程中嗜酸性粒细胞阳离子蛋白(ECP)、IL 5都起到了很重要的作用,而特异性免疫治疗能否改善患者体内这些细胞因子的状况,尚未见报道。我们对只有尘螨过敏的13例常年性变应性鼻炎(PAR)患者进行了特异性免疫治疗前、后血清和鼻灌洗液中ECP、IL 5和尘螨SIgE、TIgE的检测,并对其进行了相关的分析及临床意义的探讨。检测对象为只有尘螨皮试阳性的PAR患者13例,男5例、女8例;年龄在18～6 2岁;病程2～2 2年。即往从未进行过免疫治疗,尘螨皮试至少 。病史中也否认对其他物质过敏,在接受特异性免疫治疗期间未接受过…     

常年性鼻炎的病理生理进展

本文就鼻腔血管和神经分布及其在常年性鼻炎发病中的意义、有关的化学介质或传统的神经递质、神经肽、细胞活素和细胞、“反射亢进性鼻炎”、变应原与机体相互作用等诸多方面进行了系统的综述。     

白介素13+2044G>A基因多态性与尘螨变应性鼻炎的关系探讨

目的 对尘螨诱导引起变应性鼻炎的患者行白介素13+2044 G>A基因分型,探讨白介素13+2044 G>A基因与尘螨变应性鼻炎遗传易感性的相关性.方法 用PCR-RFLP法为97名无亲缘关系的尘螨变应性鼻炎患者和119名无血缘关系的健康汉族人行白介素13+2044 G>A基因分型.结果 尘螨变应性鼻炎组与对照组相比,...     

佛山乐从地区家具工人变应性鼻炎变应原检测分析

目的 分析佛山乐从地区家具工人变应性鼻炎变应原阳性分布情况.方法 收集2014年1月至2016年6月就诊于本院五官科的变应性鼻炎患者500例为观察组,职业均为家具工人;另选取同期本院就诊的非家具工人变应性鼻炎患者500例为对照组.进行患者血清总IgE水平与血清特异性变应原检测及变应原皮肤点刺试验,探讨两组患者吸入性变应原的阳性分布情况,分析两种变应原检测方法的一致性.结果 观察组和对照组患者血清总IgE阳性率分别为95.6％(478/500)、92.8％ (464/500),组间比较差异无统计学意义(x2=3.59,P＞0.05).血清特异性变应原检测和变应原皮肤点刺试验结果显示,两组患者螨类(粉尘螨、屋尘螨、热带螨)变应原阳性率均最高,且观察组螨类、德国小蠊、交链孢菌属、多主枝孢菌属、树木、杂草、霉菌变应原阳性率均显著高于对照组(均P＜0.05).两种变应原检测方法的一致性较好(均Kappa值＞0.6).结论 相对于非家具工人,家具工人变应性鼻炎的螨类等多种变应原阳性率均升高.     

Trends in Specific Immunotherapy for Allergic Rhinitis: A Survey of Chinese ENT Specialists

Purpose

Specific immunotherapy (SIT) is a suitable but uncommon treatment option for allergic rhinitis (AR) in China. The current understanding and attitude of Chinese ENT (ear, nose, and throat) specialists in regards to SIT is unclear. This study investigates current trends in the awareness and application status of SIT among Chinese ENT specialists.

Methods

We performed a nationwide, cross-sectional survey with a specially designed questionnaire given to 800 ENT specialists in China. A member of the trained research group conducted face-to-face interviews with each respondent.

Results

Most of the respondents considered AR (96.0%) and allergic asthma (96.0%) the most suitable indications for SIT. Of all respondents, 77.0% recommended the application of SIT as early as possible; in addition, SIT was considered ''relatively controllable and safe'' by most respondents (80.6%). The highest allergen-positive rate in AR was associated with house dust mite (47.7%) and obvious differences existed among geographical regions. Conventional subcutaneous immunotherapy was the most highly recommended treatment option (96.2%). ''The high cost of SIT'' (86.6%) and ''lack of patient knowledge of SIT'' (85.2%) were probably the main reasons for the lower clinical use of SIT in China.

Conclusions

Most cases showed that the opinions of Chinese ENT specialists appeared to be in agreement with recent SIT progress and international guidelines; however, many areas still need to enhance the standardization and use of SIT in China. Clinical guidelines for SIT require improvement; in addition, Chinese ENT specialists need continuing medical education on SIT.     

Chinese Guideline on Allergen Immunotherapy for Allergic Rhinitis: The 2022 Update

In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.     

Specific Immunotherapy Normalizes Tryptophan Concentrations in Patients with Allergic Rhinitis

Background/Aims: An immune shift towards Th2-type immunity seems to be critical in the pathogenesis of allergic asthma and rhinitis. In a previous study, we found higher serum tryptophan concentrations in patients with seasonal tree or grass pollen rhinoconjunctivitis who underwent specific immunotherapy (SCIT) than in controls, and those with the highest levels at baseline responded less well to SCIT. In the present study, we examined whether 'booster immunotherapy' after cessation of SCIT had any influence on tryptophan metabolism during follow-up. Methods: Serum concentrations of tryptophan, kynurenine and neopterin were assayed in 19 patients (mean age: 26.2 years; 6 females) allergic to grass and/or tree pollen before and after they had received a booster immunotherapy with 4 injections of an allergoid vaccine (Pollinex Quattro; Bencard Vienna, Austria) over 8 ± 3 months outside the pollen season. Results: Serum tryptophan and kynurenine concentrations decreased after booster immunotherapy (mean ± SD, before immunotherapy: 81.1 ± 14.2 μmol/l, after immunotherapy: 61.4 ± 20.9 μmol/l and before immunotherapy: 2.25 ± 0.44, after immunotherapy: 1.69 ± 0.70 μmol/l, respectively; both p < 0.01); this was especially true in those responders who also tended to have lower baseline kynurenine concentrations as compared with nonresponders (p = 0.05). Finally, a correlation between changes in tryptophan metabolism and neopterin concentrations was observed after immunotherapy. Conclusions: The decrease in tryptophan and kynurenine concentrations following booster immunotherapy in hay fever patients strengthens the hypothesis that tryptophan metabolism might be involved in the course of allergic responses. However, it is still unclear whether the abnormal tryptophan metabolism in pollinosis patients is related to indoleamine 2,3-dioxygenase and/or to a specific cytokine background.     

The Role of Anti-IgE Therapy in Combination with Allergen Specific Immunotherapy for Seasonal Allergic Rhinitis

Novel therapies that interfere specifically with immunologic mechanisms underlying allergen-induced pathology are currently in clinical evaluation. Among these is anti-IgE, which directly targets IgE serum antibodies, thus inhibiting the central mechanism of immediate-type hypersensitivity reactions. Application of anti-IgE antibodies effectively reduces IgE serum levels regardless of allergen specificity. Anti-IgE therapy has been successfully tested in patients with allergic rhinitis, asthma, and food allergy, showing significant efficacy in reducing symptom scores and the use of rescue medications. However, such therapy is limited by high costs and the requirements for permanent or every-season treatment. The advantage of specific immunotherapy (SIT) is the potential to alter the course of the disease, which has been demonstrated in patients with allergic rhinitis, insect venom allergy and, to a lesser degree, asthma. The broader application of SIT is restricted by sometimes life-threatening adverse effects. The combination of anti-IgE with SIT was suggested to be superior to each single treatment protocol in children and adolescents with allergic rhinitis. In a randomized, double-blind trial to assess the efficacy and safety of anti-IgE (omalizumab) or placebo in combination with SIT (birch pollen or grass pollen), the combination therapy reduced symptom load, the sum of daily symptom severity score plus rescue medication use, over the birch and grass pollen seasons by nearly 50% over SIT alone. These data show that the combination of anti-IgE plus SIT may be beneficial for the treatment of allergic diseases, offering improved efficacy, limited adverse effects, and potential immune-modifying effects.     

Role of miR-146a in Enforcing Effect of Specific Immunotherapy on Allergic Rhinitis

Allergic rhinitis (AR) is one of the common disorders in airway allergic inflammation. The pathogenesis of AR is unclear. It is accepted that immune deregulation is associated with the pathogenesis of AR. Recent reports suggest that a large number of micro RNAs (miR) can regulate immune functions. This study aims to investigate the role of miR-146a in an enforcing immunotherapy of AR. In this study, a mouse AR model was created. The levels of miR-146a in the mouse nasal mucosa were assessed by real time RT-PCR. A specific immunotherapy was performed in AR mice. The results showed that the AR mice had an AR-like inflammation in the nasal mucosa. Compared with naïve mice, markedly lower levels of miR-146a were detected in AR mice. The co-administration with miR-146a significantly enforced the effect of ovalbumin (OVA)-specific immunotherapy on inhibition of AR inflammation in the nasal mucosa. Further analysis showed that miR-146a induced transforming growth factor-β in dendritic cells; the latter induced naïve CD4⁺ T cells to differentiate into regulatory T cells. In conclusion, miR-146a can enforce OVA-specific immunotherapy via inducing antigen-specific regulatory T cells. miR-146a may have therapeutic potential to be used in the immunotherapy of allergic diseases.     

Serum Level of Interleukin-4 in Patients with Perennial Allergic Rhinitis During Allergen-Specific Immunotherapy

Interleukin-4 (IL-4) may play a central role in the IgE synthesis system, the development of Th-2-like cells, and co-ordination as well as the persistence of airway inflammatory process in allergic disorders. Therefore, IL-4 plays a key role in airway allergic disorders. This study aimed at investigating the serum concentrations of IL-4 in patients with perennial allergic rhinitis, with special reference to the possible changes and the clinical relevance following long-term immunotherapy. The study has demonstrated that the serum level of IL-4 in allergic rhinitis patients before immunotherapy is significantly higher than that in non-atopic individuals. However, the serum IL-4 level in allergic rhinitis patients did not decrease following anti-allergic medications but significantly decreased following immunotherapy. The percentage decrease in IL-4 was correlated significantly with the percentage decrease in specific IgE antibodies following long-term immunotherapy. Immunotherapy also significantly decreased specific IgE antibodies, but this reduction in specific IgE antibodies was not significantly correlated with the clinical improvement. In contrast, the percentage decrease in serum IL-4 was significantly correlated with the percentage decrease in symptomatic scores. The authors interpret these data to mean that immunotherapy alters T-cell cytokine profiles in the long-term, and a decline of IL-4 following immunotherapy could modulate not only production of specific IgE antibodies but also inflammatory cellular events, leading to symptomatic relief in allergic rhinitis.