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Fundamentals of laboratory diagnostics in allergology
Q3 Medicine Pub Date : 2025-02-26 DOI: 10.1007/s40629-025-00323-1
Christos Arsenis, Styliani Taka,  Chrysanthi Skevaki

The diversity of allergic disorders and their associated underlying mechanisms render allergy diagnosis particularly challenging. There is a palette of available in vivo and in vitro tests, while result interpretation must always be made in conjunction with clinical history. The focus of the present article is on laboratory diagnostics, where several diagnostic tests have been developed targeting different parts of the allergic cascade. The results of these tests may indicate the presence of clinical allergy but also provide information on disease severity, treatment options, and therapy responsiveness. First-line testing involves allergen specific IgE (sIgE) antibody measurements, and several considerations are required when choosing the exact test. Among others, the allergens to be tested, the use of allergen extracts versus molecular components, cross-reactivity aspects, cost, and geographical sensitization patterns need to be considered. There are technical distinctions between main commercially available automated platforms, which is often reflected by differences in their test results. Diagnostically challenging cases can be supplemented by tests assessing the key effector cells, i.e., basophils, mast cells, and eosinophils, as well as by tests targeting several of the released mediators, including tryptase, lipids, and histamine. Overall, non-IgE-based laboratory tests need additional standardization and research to support their clinical utility.

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引用次数: 0
Developing novel test for allergy diagnostics: using today’s biochemical techniques
Q3 Medicine Pub Date : 2025-02-14 DOI: 10.1007/s40629-025-00325-z
Eric Whitters, Kelline Rodems, Yinglei Tao, Tom de Poorter

Background

The key to moving beyond “bucket chemistry” in allergy testing is to tightly control the sourcing, analysis, and performance testing of the extracts used. It is imperative that each allergen extract be scrutinized using today’s biochemical techniques as an active part of the qualification process rather than the ones developed almost 30 years ago for the technologies of the 1990s. Characterization of allergens demystifies the source material and provides results in the clinical lab that are less ambiguous and are more closely related with the clinical status of the patient.

Methods and results

This article delivers a technical overview that outlines the requisite steps for diagnostic companies to characterize, analyze, and qualify allergen extracts, mixtures, and components integrated into their platforms. It also evaluates diverse technologies employed in both singleplex and multiplex diagnostics, highlighting the incorporation of more precisely defined biochemical materials in their product offerings.

Conclusion

The primary goal of this review is to provide laboratory professionals and clinicians with a systematic approach to ensure that extracts meet stringent performance requirements crucial for dependable allergen-specific IgE testing.

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引用次数: 0
Allergen immunotherapy based on molecular diagnostics: pediatric aspects
Q3 Medicine Pub Date : 2025-01-15 DOI: 10.1007/s40629-024-00318-4
Paolo Maria Matricardi
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引用次数: 0
Pivotal role of the optimal dose in allergen immunotherapy
Q3 Medicine Pub Date : 2025-01-02 DOI: 10.1007/s40629-024-00322-8
Pascal Werminghaus, Sven Becker, Ludger Klimek, Mandy Cuevas, Martin Rosewich, Frauke Hermanns, Anke Graessel, Pieter-Jan de Kam,  Matthias F. Kramer MD

The transitioning of named patient products (NPPs) of therapy allergens is regulated under the German therapy allergen ordinance (TAO) since 2008. The establishment of a sound dose–response relationship constitutes a pivotal aspect in clinical development programs of drugs in general. Up to now, there are only few comprehensive studies dedicated to the determination of a dose–response relationship in allergen immunotherapy (AIT) because of various challenges. Among these aggravating factors are high placebo effects, variability of trial endpoints and especially for native allergens a narrow therapeutic window and safety profile. The phase II trials of the modified allergen tyrosine associated—monophosphoryl lipid A (MATA MPL) platform for birch and grasses established convincing and significant dose–response relationships decisive for AIT product optimization. The significant dose–response relationship for birch and grass allergoids reached an efficacy plateau and allowed the definition of critical milestones in drug development such as the median effective dose (ED50) for the MATA MPL platform combining modified allergens (allergoids) with microcrystalline tyrosine (MCT) and MPL in an adjuvant system. This marked a pivotal milestone in AIT drug development allowing the definition of the “optimal dose” (optimal risk–benefit ratio) to be taken forward to phase III trial. The MATA MPL platform is characterized by a scientifically sound dose–response relationship across allergens which underlines the pivotal role of a well-defined optimal dose as a success factor for phase III.

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引用次数: 0
Position paper dupilumab and vaccination
Q3 Medicine Pub Date : 2024-12-18 DOI: 10.1007/s40629-024-00319-3
Sebastian M. Schmidt, Tobias Ankermann, Carl-Peter Bauer, Peter Fischer, Monika Gappa, Michael Gerstlauer, Matthias V. Kopp, Susanne Lau, Christiane Lex, Bernd Mischo, Bianca Schaub, Thomas Spindler, Christian Vogelberg

The extension of the approval of dupilumab for the treatment of severe atopic dermatitis in children 6 months of age and older in Germany creates a potential conflict with the administration of live attenuated vaccines. According to the product information, the administration of live attenuated vaccines is contraindicated during ongoing dupilumab therapy. This position paper, written by specialists in pediatric immunology and allergology from Germany and Switzerland, aims to support pediatricians to provide their patients with the best possible treatment with dupilumab and appropriate vaccinations based on the currently available evidence, including statements and advice for clinical situations. The practical implementation of these statements requires a differentiated approach. The position paper covers the situation in Germany, with special attention to the recommendations of the STIKO (Standing Committee on Vaccination) and the Robert Koch Institute for German-speaking countries and the legal situation here.

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引用次数: 0
Sensitizations to pollen differ between Central European and Sub-Saharan African atopic dermatitis patients
Q3 Medicine Pub Date : 2024-10-21 DOI: 10.1007/s40629-024-00313-9
Danielle Fehr, Muriel Rentschler, Fandresena Sendrasoa, Nick Li, Anna White, Meike Distler, Claudia Lang, Gloria Masenga, Nelson Mosha, George Semango, Clara Clemens, Tahinamandranto Rasamoelina, Abel Hermann Soankasina, Fahafahantsoa Rapelanoro Rabenja, Daudi Mavura, John Elisante Masenga, Peter Schmid-Grendelmeier, Marie-Charlotte Brüggen MD PhD

Atopic dermatitis (AD) is often associated with allergic comorbidities, such as allergic asthma or allergic rhinoconjunctivitis (ARC). Sensitizations to pollen can directly impact AD, as patients can experience exacerbation during pollen season. This study aims to gain more insights into the pollen sensitization patterns of AD patients in Central Europe compared with sub-Saharan Africa (SSA).

We performed a case–control study involving a total of 90 participants: 20 AD patients and 10 healthy controls (HC) each from Switzerland (CH), Tanzania (TZ), and Madagascar (MD). We collected clinical data and serum samples and performed a multiplex IgE test (ALEX2 Allergy Explorer, MacroArray Diagnostics, Vienna, Austria).

The prevalence of ARC and asthma in AD patients was similar in all countries (ARC: 60% TZ, 70% CH, 75% MD; asthma: 25% TZ, 30% CH, 20% MD). Total IgE levels were significantly higher in both SSA HC populations compared with the Swiss HC. The analysis of specific IgE levels revealed major differences in sensitization patterns between Africa and Europe, especially regarding grass pollen allergens. Swiss AD patients were sensitized to various grass pollen such as Bahia grass, Bermuda grass, common reed, perennial ryegrass, rye, and timothy grass. However, these allergens were irrelevant in the SSA population: no AD patient or HC subject was sensitized to the tested grass pollen.

The considerably different sensitization patterns between European and SSA AD patients warrant the development of allergy testing and desensitization therapies tailored to the African setting. Therefore, there is a need to characterize local pollen types and counts.

特应性皮炎(AD)通常伴有过敏性合并症,如过敏性哮喘或过敏性鼻结膜炎(ARC)。对花粉过敏会直接影响特应性皮炎,因为患者会在花粉季节病情加重。我们进行了一项病例对照研究,共有 90 人参与:分别来自瑞士(CH)、坦桑尼亚(TZ)和马达加斯加(MD)的 20 名 AD 患者和 10 名健康对照(HC)。我们收集了临床数据和血清样本,并进行了多重 IgE 检测(ALEX2 Allergy Explorer,MacroArray Diagnostics,奥地利维也纳)。所有国家的 AD 患者的 ARC 和哮喘发病率相似(ARC:60% TZ、70% CH、75% MD;哮喘:25% TZ、30% CH、20% MD)。与瑞士高危人群相比,SSA 和瑞士高危人群的总 IgE 水平明显较高。对特异性 IgE 水平的分析表明,非洲和欧洲的致敏模式存在很大差异,尤其是在草花粉过敏原方面。瑞士 AD 患者对多种草花粉过敏,如巴伊亚草、百慕大草、普通芦苇、多年生黑麦草、黑麦和梯牧草。欧洲和非洲撒哈拉以南地区 AD 患者的致敏模式大相径庭,因此需要开发适合非洲环境的过敏测试和脱敏疗法。因此,有必要确定当地的花粉类型和数量。
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引用次数: 0
Requirements for regulatory acceptance of biomarkers 监管机构接受生物标记物的要求
Q3 Medicine Pub Date : 2024-10-17 DOI: 10.1007/s40629-024-00312-w
Hilke Zander, Jörg Engelbergs

Generally, biomarkers could increase the success rate of medicinal product developments and as a consequence accelerate the availability of new therapeutics with an improved benefit–risk relationship. Therefore, patient identification based on predictive biomarkers is becoming increasingly important in all therapeutic areas [1]. The increasing use of predictive biomarker-guided-personalized (precision) medicine warrants the discovery of novel biomarkers as measurable indicators of physiopathological conditions [2]. Biomarkers can be used for diagnostics and prognostics, monitoring disease progression, but also to select the most effective therapy and to predict the treatment outcome [3, 4]. The current article provides a short focus on the regulatory definition of a biomarker and the biomarker qualification process of the European Medicines Agency (EMA). With the evolving landscape, the new Regulation (EU) 2017/746 on in vitro medical devices (IVDR) [5] introduces important changes in the EU legal framework for IVDs especially by legally defining for the first time “companion diagnostic” devices (CDx). Challenges in the codevelopment of CDx and medicinal products are highlighted to provide scientific–regulatory considerations in this complex regulatory field.

一般来说,生物标志物可以提高医药产品开发的成功率,从而加快新疗法的推出,改善获益与风险之间的关系。因此,基于预测性生物标记物的患者识别在所有治疗领域都变得越来越重要[1]。随着预测性生物标记物引导的个性化(精准)医疗的应用日益广泛,需要发现新型生物标记物作为生理病理状况的可测量指标[2]。生物标志物可用于诊断和预后、监测疾病进展,也可用于选择最有效的疗法和预测治疗结果[3, 4]。本文简要介绍了生物标记物的监管定义以及欧洲药品管理局(EMA)的生物标记物鉴定程序。随着形势的不断发展,关于体外医疗器械(IVDR)的新法规(欧盟)2017/746[5]对欧盟 IVD 法律框架引入了重要变化,特别是首次从法律上定义了 "辅助诊断 "设备(CDx)。本文强调了 CDx 和医药产品的代码开发所面临的挑战,为这一复杂的监管领域提供了科学监管方面的考虑因素。
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引用次数: 0
Impact of obesity on allergic respiratory diseases and on mental and cognitive performance 肥胖对过敏性呼吸道疾病以及智力和认知能力的影响
Q3 Medicine Pub Date : 2024-10-14 DOI: 10.1007/s40629-024-00308-6
Nora Geissler, Erika Garner-Spitzer, Aleksandra Inic-Kanada, Daniela D. Pollak,  Ursula Wiedermann

Obesity and allergies are among the most common diseases of our civilization. Given the simultaneous rise in the prevalence of these diseases in recent years, a potential causal link between the two has been proposed. In particular, obese patients are at an increased risk of developing bronchial asthma, likely due to mechanical restrictions but also to metabolic changes that adversely affect immune function. Neuroscience studies have also shown that obesity can lead to impaired brain function and mental health. In the following review, we will take a closer look at our studies that focus on the influence of obesity on allergic diseases and cognitive performance.

Both human studies and animal models (mice) have shown that obesity leads to increased allergic responses in the airways. Our studies in a mouse model of obesity confirm that an obese phenotype is associated with increased allergic sensitization and manifestation. These changes are associated with significant shifts in the composition of the gut microbial flora. The microbiome changes are further associated with allergic airway inflammation and an increased incidence of T helper 1 (Th1) type pulmonary macrophages. Interestingly, despite the changes in the microbiome, it is possible to effectively prevent allergy development by inducing oral tolerance. Furthermore, it was observed that obese mice show increased signs of anxiety and depression, as well as reduced cognitive performance.

Obesity is a complex metabolic disease that significantly impacts our body’s gut microbiome and immune system, resulting in an increased incidence of allergic asthma and neurological/psychological changes. Attention should be given to both the prophylactic and therapeutic measures to mitigate the impact of obesity, including oral tolerance for managing existing allergic diseases.

肥胖症和过敏症是人类文明中最常见的疾病之一。鉴于近年来这两种疾病的发病率同时上升,有人提出这两者之间可能存在因果关系。特别是,肥胖患者患支气管哮喘的风险增加,这可能是由于机械性限制,也可能是由于新陈代谢的变化对免疫功能产生了不利影响。神经科学研究也表明,肥胖会导致大脑功能和心理健康受损。在下面的综述中,我们将仔细研究肥胖对过敏性疾病和认知能力的影响。人类研究和动物模型(小鼠)都表明,肥胖会导致气道过敏反应增加。我们在肥胖小鼠模型中的研究证实,肥胖表型与过敏敏感性和过敏表现的增加有关。这些变化与肠道微生物菌群组成的显著变化有关。微生物群的变化还与过敏性气道炎症和 T 辅助细胞 1(Th1)型肺巨噬细胞发病率增加有关。有趣的是,尽管微生物群发生了变化,但通过诱导口服耐受性仍可有效预防过敏的发生。此外,研究还发现,肥胖小鼠的焦虑和抑郁症状增加,认知能力下降。肥胖是一种复杂的代谢性疾病,会严重影响人体的肠道微生物组和免疫系统,导致过敏性哮喘发病率增加和神经/心理变化。应关注减轻肥胖影响的预防和治疗措施,包括管理现有过敏性疾病的口服耐受性。
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引用次数: 0
One health: the impact of environment, detergents and hygiene on barrier, microbiome and allergy 同一健康:环境、清洁剂和卫生对屏障、微生物群和过敏的影响
Q3 Medicine Pub Date : 2024-10-09 DOI: 10.1007/s40629-024-00307-7
Hanna Mayerhofer,  Isabella Pali-Schöll PhD

A variety of body surfaces, such as skin and mucosal membranes—from the nasopharyngeal area to the lungs, uterus, vaginal area, and digestive tract—contain complex microbial ecosystems that are tailored to the specifics of the respective niche [1].

The so-called dysbiosis—a disadvantageous change in the composition of the microbiome—is associated with the pathogenesis of a variety of diseases [2]. Gastrointestinal as well as cardiovascular, metabolic, neurodegenerative, psychological, oncological, and also allergic diseases have been linked to microbial dysbiosis. Susceptibility to allergies can be due to genetic predisposition; in addition, extrinsic factors from today’s lifestyle increasingly contribute to microbiome changes, but also to the disruption of the skin and mucosal barrier and thus to the development of allergies [3].

Gisela, a fictional farmer, guides us through this review. She is representative of adults and children of all genders in industrialized countries. During her daily routine, the skin and mucosal microbiome is influenced by a variety of exogenous factors. These include everyday personal hygiene products, detergents for laundry and dishes, food, medication, animal contact, and exposure to various outdoor environments. Gisela’s daily routine will illustrate how the human microbiome and the skin barrier are modified in positive or negative ways, and how this could influence the development of allergies. Furthermore, potential measures for the prevention and management of dysbiosis will be discussed in terms of examples of alternative products and behaviors.

从鼻咽部到肺部、子宫、阴道和消化道等各种体表,如皮肤和粘膜,都包含着复杂的微生物生态系统,这些生态系统是根据各自生态位的具体情况量身定制的[1]。所谓的菌群失调--微生物组成的不利变化--与多种疾病的发病机制有关[2]。胃肠道疾病、心血管疾病、新陈代谢疾病、神经退行性疾病、心理疾病、肿瘤疾病以及过敏性疾病都与微生物菌群失调有关。过敏症的易感性可能是遗传所致;此外,当今生活方式中的外在因素也越来越多地导致微生物群发生变化,同时也破坏了皮肤和粘膜屏障,从而导致过敏症的发生[3]。她是工业化国家所有性别的成人和儿童的代表。在她的日常生活中,皮肤和粘膜微生物群受到各种外源因素的影响。这些因素包括日常个人卫生用品、洗衣和洗碗用的洗涤剂、食物、药物、动物接触以及暴露于各种户外环境。吉塞拉的日常生活将说明人体微生物群和皮肤屏障是如何以积极或消极的方式发生改变的,以及这可能如何影响过敏症的发生。此外,还将通过替代产品和行为举例,讨论预防和管理菌群失调的潜在措施。
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引用次数: 0
Discharge management after anaphylaxis 过敏性休克后的出院管理
Q3 Medicine Pub Date : 2024-10-02 DOI: 10.1007/s40629-024-00306-8
Valentina Faihs,  Johannes Ring, Knut Brockow, Kirsten Beyer, Ernst Rietschel, Sabine Schnadt, Britta Stöcker, Regina Treudler, Margitta Worm, Ludger Klimek

People who have suffered from anaphylaxis often experience far-reaching consequences in everyday life. Unfortunately, discharge management after successful acute treatment is often still inadequate. In order to prevent further reactions in the future and improve the patient’s quality of life, there are several points that should be addressed or followed upon discharge from acute treatment. These include taking a detailed medical history to identify potential triggers, documenting the acute therapy, recommending further allergological assessment and prescribing an emergency kit for self-help including an adrenaline auto-injector—with education and practice on how to use it, including a written emergency plan. In addition, recommendations for avoiding potential triggers and information on patient organizations are helpful. This article aims to provide an up-to-date overview of discharge management after successful acute treatment of anaphylaxis. Remember: “After anaphylaxis also means potentially before the next anaphylaxis.”

过敏性休克患者通常会在日常生活中遭受深远的影响。遗憾的是,急性期治疗成功后的出院管理往往仍然不足。为了防止今后再次发生过敏反应并改善患者的生活质量,急性期治疗后出院时应注意或遵循以下几点。这些要点包括:详细询问病史以确定潜在的诱发因素;记录急性治疗过程;建议进一步进行过敏评估;开具包括肾上腺素自动注射器在内的自救应急包,并就如何使用该应急包进行教育和练习,包括书面应急计划。此外,避免潜在诱因的建议和患者组织信息也很有帮助。本文旨在提供过敏性休克急性期治疗成功后出院管理的最新概述。请记住:"过敏性休克发生后也意味着有可能在下一次过敏性休克发生之前"。
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引用次数: 0
期刊
Allergo Journal International
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