Peanut allergy

花生过敏
  • 文章类型: Journal Article
    花生过敏因其发病率高、症状严重而受到全世界的关注,激发了对花生过敏原超灵敏检测方法的需求。在这里,我们成功开发了一种新型的电化学传感器,用于超灵敏检测花生中存在的主要致敏蛋白Arah1。导电镍原子锚定的氢键有机框架(PFC-73-Ni)被用作对氢醌(HQ)氧化的优异电催化剂,以产生可读的电流信号。开发的电化学传感器为Arah1提供宽线性范围(1-120nM)和低检测限(0.26nM)。在非花生食品样品的标准添加检测中,该方法的回收率为95.00%至107.42%。此外,所开发的电化学方法已在实际样品中进行了验证,并与从商业ELISA试剂盒获得的结果具有良好的一致性。这表明所建立的Arah1检测方法是一种有前途的花生过敏预防工具。
    Peanut allergy has garnered worldwide attention due to its high incidence rate and severe symptoms, stimulating the demand for the ultrasensitive detection method of peanut allergen. Herein, we successfully developed a novel electrochemical aptasensor for ultrasensitive detection Ara h1, a major allergenic protein present in peanuts. A conductive nickel atoms Anchored Hydrogen-Bonded Organic Frameworks (PFC-73-Ni) were utilized as excellent electrocatalysts toward hydroquinone (HQ) oxidation to generate a readable current signal. The developed electrochemical aptasensor offers wide linear range (1-120 nM) and low detection limit (0.26 nM) for Ara h1. This method demonstrated a recovery rate ranging from 95.00% to 107.42% in standard addition detection of non-peanut food samples. Additionally, the developed electrochemical method was validated with actual samples and demonstrated good consistency with the results obtained from a commercial ELISA kit. This indicates that the established Ara h1 detection method is a promising tool for peanut allergy prevention.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    背景:很少有研究检查口服免疫治疗(OIT)后的长期结果;没有研究检查与不同临床结果相关的长期风险和益处(脱敏,residence).
    方法:完成益生菌和花生口服免疫疗法(PPOIT)-003随机试验的参与者被纳入一项后续研究,PPOIT-003LT.花生摄入,reactions,并对健康相关生活质量(HRQOL)进行前瞻性监测.治疗后1年和2年的结果按治疗组和OIT后的临床结果(缓解,脱敏无缓解[DWR],过敏)。
    结果:86%(151/176)的合格儿童登记。PPOIT(86.7%)和OIT(78.7%)组治疗后2年的花生摄入相似,两者均高于安慰剂(10.3%)。所有治疗和临床结果组的反应随着时间的推移而减少(PPOIT31.7%至23.3%,OIT37.7%至19.7%,安慰剂13.8%至6.9%;缓解27.5%至15.9%;DWR57.9%至36.8%;过敏11.6%至7%)。治疗后2年,缓解和过敏参与者报告反应的比例相似(RD0.09(95CI-0.03,0.20),p=.127),而更多的DWR参与者报告的反应比缓解(缓解与DWR:RD-0.21(95CI-0.39;-0.03),p=.02)和过敏(DWR与过敏:RD0.30(95CI0.13,0.47),p=.001)参与者。治疗后2年,0%缓解与5.3%DWR和2.3%过敏参与者报告使用肾上腺素注射器。与两个DWR相比,缓解参与者的HRQOL改善(基线校正)明显更大(MD-0.54(95CI-0.99,-0.10),p=.017)和过敏(MD-0.82(95CI-1.25,-0.38),p<.001)。
    结论:治疗后2年,缓解的参与者报告反应较少,与DWR和过敏参与者相比,严重的反应较少,HRQOL改善较大,表明缓解是患者首选的治疗结果,而不是脱敏或保持过敏。
    BACKGROUND: Few studies have examined long-term outcomes following oral immunotherapy (OIT); none have examined long-term risks and benefits associated with distinct clinical outcomes (desensitization, remission).
    METHODS: Participants completing the probiotic and peanut oral immunotherapy (PPOIT) -003 randomized trial were enrolled in a follow-on study, PPOIT-003LT. Peanut ingestion, reactions, and health-related quality of life (HRQOL) were monitored prospectively. Outcomes at 1-year and 2-years post-treatment were examined by treatment group and by post-OIT clinical outcome (remission, desensitization without remission [DWR], allergic).
    RESULTS: 86% (151/176) of eligible children enrolled. Post-treatment peanut ingestion at 2-years post-treatment were similar for PPOIT (86.7%) and OIT (78.7%) groups, both higher than placebo (10.3%). Reactions reduced over time for all treatment and clinical outcome groups (PPOIT 31.7% to 23.3%, OIT 37.7% to 19.7%, placebo 13.8% to 6.9%; remission 27.5% to 15.9%; DWR 57.9% to 36.8%; allergic 11.6% to 7%). At 2-years post-treatment, similar proportions of remission and allergic participants reported reactions (RD 0.09 (95%CI -0.03, 0.20), p = .127), whereas more DWR participants reported reactions than remission (remission vs DWR: RD -0.21 (95%CI -0.39; -0.03), p = .02) and allergic (DWR vs allergic: RD 0.30 (95%CI 0.13, 0.47), p = .001) participants. At 2-years post-treatment, 0% remission versus 5.3% DWR versus 2.3% allergic participants reported adrenaline injector usage. Remission participants had significantly greater HRQOL improvement (adjusted for baseline) compared with both DWR (MD -0.54 (95%CI -0.99, -0.10), p = .017) and allergic (MD -0.82 (95%CI -1.25, -0.38), p < .001).
    CONCLUSIONS: By 2-years post-treatment, remission participants reported fewer reactions, less severe reactions and greater HRQOL improvement compared with DWR and allergic participants, indicating that remission is the patient-preferred treatment outcome over desensitization or remaining allergic.
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  • 文章类型: Journal Article
    背景:现有的治疗策略受到长时间的挑战以达到效果,并且通常需要频繁的给药。花生过敏个体将受益于在给药的几天内提供针对意外暴露的快速保护的治疗剂,同时携带很少的不良反应风险。
    目的:以来自过敏个体的人IgE单克隆抗体(mAb)为指导,我们试图开发一种利用已知的过敏原特异性IgG4抗体保护作用的治疗方法.
    方法:我们将我们的单细胞RNA测序SEQSIFTER™平台应用于来自花生过敏个体的全血样品,以发现IgEmAb。然后通过用IgG4替换IgE恒定区同时保留变应原特异性可变区来对这些进行类别转换。体外肥大细胞活化试验(MATs),嗜碱性粒细胞活化试验(BAT),酶联免疫吸附测定(ELISA),并使用体内花生过敏小鼠模型来评估其特异性,亲和力,和这些重组IgG4mAb的活性。
    结果:我们确定人花生特异性IgEmAb主要靶向Arah2和Arah6上的免疫显性表位,重组IgG4mAb有效阻断了这些表位。IGNX001,两种高亲和力IgG4mAb的混合物,在花生过敏小鼠模型中,针对花生介导的肥大细胞活化以及在胃内花生攻击后的过敏反应提供了强大的保护。
    结论:我们开发了一种花生特异性IgG4抗体治疗药物,具有令人信服的临床前疗效,从人口统计学和地理上不同个体的大量人单克隆IgE抗体开始。这些结果值得对IGNX001进行进一步的临床研究,并强调了将这种治疗开发策略应用于其他食物和环境过敏的机会。
    BACKGROUND: Existing therapeutic strategies are challenged by long times to achieve effect and often require frequent administration. Peanut allergic individuals would benefit from a therapeutic that provides rapid protection against accidental exposure within days of administration while carrying little risk of adverse reactions.
    OBJECTIVE: Guided by the repertoire of human IgE monoclonal antibodies (mAbs) from allergic individuals, we sought to develop a treatment approach leveraging the known protective effects of allergen-specific IgG4 antibodies.
    METHODS: We applied our single-cell RNA sequencing SEQ SIFTER™ platform to whole blood samples from peanut allergic individuals to discover IgE mAbs. These were then class-switched by replacing the IgE constant region with IgG4 while retaining the allergen-specific variable regions. In vitro mast cell activation tests (MATs), basophil activation tests (BATs), enzyme-linked immunosorbent assays (ELISAs), and an in vivo peanut allergy mouse model were used to evaluate the specificity, affinity, and activity of these recombinant IgG4 mAbs.
    RESULTS: We determined that human peanut-specific IgE mAbs predominantly target immunodominant epitopes on Ara h 2 and Ara h 6 and that recombinant IgG4 mAbs effectively blocked these epitopes. IGNX001, a mixture of two such high-affinity IgG4 mAbs, provided robust protection against peanut-mediated mast cell activation in vitro as well as against anaphylaxis upon intragastric peanut challenge in a peanut allergy mouse model.
    CONCLUSIONS: We developed a peanut-specific IgG4 antibody therapeutic with convincing preclinical efficacy starting from a large repertoire of human monoclonal IgE antibodies from demographically and geographically diverse individuals. These results warrant further clinical investigation of IGNX001 and underscore the opportunity for the application of this therapeutic development strategy in other food and environmental allergies.
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  • 文章类型: Journal Article
    食物过敏(FA)估计会影响多达10%的人口,并且是一个日益严重的健康问题。FA是由粘膜免疫系统无法建立或维持对无害饮食抗原的免疫耐受引起的。IgE生产,以及暴露于食物过敏原后释放组胺和其他介质。在不同的FA中,花生过敏的严重过敏反应发生率最高,包括全身过敏反应.尽管最近FDA批准了花生口服免疫疗法和其他研究性免疫疗法,停止治疗后可能会失去保护,这表明这些疗法不能解决驱动FA的潜在免疫反应。我们的实验室已经表明,肝定向基因治疗与腺相关病毒(AAV)载体诱导转基因产物特异性调节性T细胞(Tregs),根除预先存在的致病性抗体,并在几种模型中防止过敏反应,包括卵清蛋白诱导的FA。在表皮花生过敏小鼠模型中,四种花生抗原Arah1,Arah2,Arah3和Arah6的肝AAV共表达或Arah3的单一表达阻止了花生过敏的发展。由于FA患者显示Treg数量和/或功能减少,我们相信我们的方法可能会解决这个未满足的需求。
    Food allergy (FA) is estimated to impact up to 10% of the population and is a growing health concern. FA results from a failure in the mucosal immune system to establish or maintain immunological tolerance to innocuous dietary antigens, IgE production, and the release of histamine and other mediators upon exposure to a food allergen. Of the different FAs, peanut allergy has the highest incidence of severe allergic responses, including systemic anaphylaxis. Despite the recent FDA approval of peanut oral immunotherapy and other investigational immunotherapies, a loss of protection following cessation of therapy can occur, suggesting that these therapies do not address the underlying immune response driving FA. Our lab has shown that liver-directed gene therapy with an adeno-associated virus (AAV) vector induces transgene product-specific regulatory T cells (Tregs), eradicates pre-existing pathogenic antibodies, and protects against anaphylaxis in several models, including ovalbumin induced FA. In an epicutaneous peanut allergy mouse model, the hepatic AAV co-expression of four peanut antigens Ara h1, Ara h2, Ara h3, and Ara h6 together or the single expression of Ara h3 prevented the development of a peanut allergy. Since FA patients show a reduction in Treg numbers and/or function, we believe our approach may address this unmet need.
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  • 文章类型: Journal Article
    花生过敏(PA)是一种IgE介导的食物过敏,具有可变的临床结果。轻度至重度症状影响各种器官,经常,胃肠道.肠道来源的IgE抗体在胃肠道PA症状中的作用知之甚少。这项研究旨在检查PA中的粪便IgE反应,作为一种新的患者内分型方法。
    方法:从花生过敏和健康儿童(n=26)收集粪便和血清样本,以使用多重检测方法鉴定IgE和细胞因子。Shotgun宏基因组学DNA测序和过敏原数据库比较使鉴定与已知过敏原具有同源性的微生物肽成为可能。
    结果:与对照组相比,粪便IgE特征显示13种过敏原的广泛多样性和水平增加,包括食物,毒液,联系人,和呼吸道过敏原(P<.01-.0001)。总的来说,与PA患者的血清IgE模式相比,粪便IgE模式呈负相关,花生过敏原的差异最大(P<0.0001)。对于粪便IgE识别的83%的过敏原,我们发现了PA患者肠道微生物组的细菌同源物(例如,类似于术蛋白的鲍曼不动杆菌与第2号法案,109/124个氨基酸相同)。与对照组相比,PA患者粪便IgA水平较高,IL-22和自身IgE与它们自身的粪便蛋白结合(P<.001)。最后,粪便IgE水平与腹痛评分相关(P<0.0001),提示局部IgE产生和临床结果之间的联系。
    结论:肠粘膜中的粪便IgE释放可能是严重腹痛的潜在机制,这是通过漏肠上皮细胞与PA中的反共生TH2反应之间的关联。
    UNASSIGNED: Peanut allergy (PA) is an IgE-mediated food allergy with variable clinical outcomes. Mild-to-severe symptoms affect various organs and, often, the gastrointestinal tract. The role of intestine-derived IgE antibodies in astrointestinal PA symptoms is poorly understood. This study aimed to examine fecal IgE responses in PA as a novel approach to patient endotyping.
    METHODS: Feces and serum samples were collected from peanut-allergic and healthy children (n=26) to identify IgE and cytokines using multiplex assays. Shotgun metagenomics DNA sequencing and allergen database comparisons made it possible to identify microbial peptides with homology to known allergens.
    RESULTS: Compared to controls, fecal IgE signatures showed broad diversity and increased levels for 13 allergens, including food, venom, contact, and respiratory allergens (P<.01-.0001). Overall, fecal IgE patterns were negatively correlated compared to sera IgE patterns in PA patients, with the greatest differences recorded for peanut allergens (P<.0001). For 83% of the allergens recognized by fecal IgE, we found bacterial homologs from PA patients\' gut microbiome (eg, thaumatin-like protein Acinetobacter baumannii vs Act d 2, 109/124 aa identical). Compared to controls, PA patients had higher levels of fecal IgA, IL-22, and auto-IgE binding to their own fecal proteins (P<.001). Finally, levels of fecal IgE correlated with abdominal pain scores (P<.0001), suggesting a link between local IgE production and clinical outcomes.
    CONCLUSIONS: Fecal IgE release from the intestinal mucosa could be an underlying mechanism of severe abdominal pain through the association between leaky gut epithelia and anticommensal TH2 responses in PA.
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  • 文章类型: Journal Article
    哮喘是影响儿童和成人的最常见的慢性健康状况之一。它与许多合并症有关,尤其是那些沿着过敏光谱的人,如特应性皮炎,过敏性鼻炎,和食物过敏。哮喘和食物过敏之间的关系涉及预后,管理,并了解严重反应的风险。这两种情况都是异质的,并且可以随着时间的推移而变化,这就需要一种个性化的咨询和管理方法。长期以来,哮喘患者食物过敏死亡风险增加的关联并不像以前认为的那样简单或具体。对于临床医生来说,重要的是要了解哮喘与食物过敏之间关系的证据,以参与与患者的共同决策和咨询。这篇综述将提供围绕哮喘和食物过敏的细微差别关系的背景和新观点。
    Asthma is one of the most common chronic health conditions that affect children and adults. It is associated with many comorbid conditions, particularly those along the allergic spectrum, such as atopic dermatitis, allergic rhinitis, and food allergy. The relationship between asthma and food allergies involves prognosis, management, and understanding of risk for severe reactions. Both conditions are heterogeneous and can change over time, which necessitates an individualized approach toward counseling and management. Long-standing associations of an increased risk for food allergy fatality in individuals who have asthma is not as straightforward or concrete as previously believed. It is important for clinicians to have a current understanding of the evidence about the relationship between asthma and food allergy to participate in shared decision-making and counseling with patients. This review will offer background and new perspective surrounding the nuanced relationship of asthma and food allergy.
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  • 文章类型: Journal Article
    由于厌恶食物,患者和家庭的长期每日给药可能具有挑战性。给药方案,以及病人的年龄。少数长期研究表明,每日剂量低与长期通过高剂量挑战有关。而高剂量维持可以保护更长的回避间隔。我们回顾了花生的数据,并为您的患者提出了几种策略。
    Long term daily dosing for patients and families may be challenging due to food aversions, dosing protocols, and age of the patient. The few long term studies suggest that low quantity daily dosing is associated with passing higher dose challenges over the long term, whereas high dose maintenance may protect for longer avoidance intervals. We review the data for peanut and suggest several strategies for your patients.
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  • 文章类型: Journal Article
    背景:食物过敏动物模型是理解过敏机制和评估潜在脱敏方法功效的重要工具。通过灌胃致敏在小鼠中诱导过敏的有效性各不相同。腹膜内方法可以引发全身过敏反应,然而,它缺乏解剖学相关性。因此,在小鼠中需要统一和可靠的过敏诱导方法。胶带剥离可以模拟特应性皮炎(AD),人类终生花生过敏的前兆。此外,皮肤损伤会引发皮肤警报的上调和小肠肥大细胞的扩张,两者都与过敏发展有关。
    方法:我们在花生过敏的小鼠模型中标准化了基于皮肤的致敏方法,使用皮肤胶带剥离,然后应用过敏原。我们将这种方法与胃内致敏进行了比较。
    结果:皮肤致敏导致肥大细胞增多,杯状细胞,和小肠中的嗜酸性粒细胞,全身IgE水平升高,鼠肥大细胞蛋白酶-1(mMCP-1),组胺,和外周血中的嗜酸性粒细胞活性。此外,它导致了明显的低温反应,致敏后1个月进行口头攻击后死亡率接近30%。
    结论:我们的研究为诱导小鼠花生过敏提供了一种标准化且易于重复的方法,也可以适用于其他食物过敏原。
    BACKGROUND: Animal models for food allergies serve as crucial tools in understanding allergy mechanisms and assessing the efficacy of potential desensitization methods. The effectiveness of inducing allergies in mice through intragastric lavage sensitization varies. The intraperitoneal method can trigger systemic anaphylaxis, however it lacks anatomical relevance. Hence, a uniform and reliable allergy induction method in mice is required. Tape -stripping can mimic atopic dermatitis (AD), a precursor to lifelong peanut allergies in humans. Furthermore, skin damage triggers the upregulation of skin alarmins and the expansion of small-intestinal mast cells, both implicated in allergy development.
    METHODS: We standardized a skin-based sensitization method in a mouse model of peanut allergy using skin tape-stripping followed by allergen application. We compared this method with intragastric sensitization.
    RESULTS: Skin-based sensitization led to increased mast cells, goblet cells, and eosinophils in the small intestine, elevated systemic IgE levels, murine mast cell protease-1 (mMCP-1), histamine, and eosinophilic activity in peripheral blood. Moreover, it resulted in a significant hypothermic response, with nearly 30% mortality following an oral challenge one-month post-sensitization.
    CONCLUSIONS: Our research offers a standardized and readily reproducible method for inducing peanut allergy in mice, which could also be adapted for other food allergens.
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  • 文章类型: Journal Article
    背景:对花生和树坚果的过敏是西班牙食物过敏的常见原因,脂质转移蛋白(LTP)是最常见的全变应原。LTP致敏通常导致多种食物组敏感性,导致过度限制饮食,阻碍患者的生活质量。这项研究旨在评估对LTP敏感的儿童对花生和坚果(榛子和核桃)的耐受性,有可能减轻对这种饮食的需求。
    方法:这项前瞻性研究招募了被诊断为对花生过敏的个体,榛子,或者核桃.数据是从医疗记录中收集的,包括人口统计学和临床病史。过敏评估包括使用商业提取物和相关坚果的皮肤点刺测试,以及对坚果及其主要分子成分的总IgE和特异性IgE的测量。表现出积极的LTP致敏而没有对种子储存蛋白致敏的参与者接受了开放的口服坚果挑战。
    结果:共有75人被标记为对花生过敏,44到榛子,包括51个核桃。他们都接受了与有罪的坚果的公开口头挑衅测试,表现出较高的容忍率。98.6%的患者对花生耐受,97.72%耐受榛子,84.3%耐受核桃。
    结论:研究结果表明,大多数对花生过敏的患者,榛子,或者核桃,由于LTP致敏和缺乏对种子储存蛋白的IgE反应性,可以忍受这些坚果。这支持需要个性化的坚果耐受性评估,以避免不必要的饮食限制。
    BACKGROUND: Allergy to peanuts and tree nuts is a common cause of food allergy in Spain, with lipid transfer proteins (LTP) being the most frequently recognized panallergen. LTP sensitization often leads to multiple food group sensitivities, resulting in overly restrictive diets that hinder patient\'s quality of life. This study aimed to assess the tolerance of peanuts and tree nuts (hazelnuts and walnuts) in children sensitized to LTP, potentially mitigating the need for such diets.
    METHODS: This prospective study enrolled individuals diagnosed with allergy to peanuts, hazelnuts, or walnuts. Data were collected from medical records, including demographics and clinical history. Allergological assessment comprised skin prick tests using commercial extracts and the nuts in question, alongside measurements of total and specific IgE to nuts and their primary molecular components. Participants showing positive LTP sensitization without sensitization to seed storage proteins underwent open oral nut challenges.
    RESULTS: A total of 75 individuals labeled as allergic to peanuts, 44 to hazelnuts, and 51 to walnuts were included. All of them underwent an open oral provocation test with the incriminated nut, showing a high tolerance rate. Peanut was tolerated by 98.6% of patients, 97.72% tolerated hazelnut, and 84.3% tolerated walnut.
    CONCLUSIONS: The findings suggest that the majority of patients allergic to peanuts, hazelnuts, or walnuts, due to LTP sensitization and lacking IgE reactivity to seed storage proteins, can tolerate these nuts. This supports the need for personalized nut tolerance assessments to avoid unnecessary dietary restrictions.
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