Abstract：
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.
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.
摘要：
■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。
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。
