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Abstract：
BACKGROUND: The mechanisms contributing to clinical immune tolerance remain incompletely understood. This study provides evidence for specific immune mechanisms that are associated with a model of operationally defined clinical tolerance.
OBJECTIVE: Our overall objective was to study laboratory changes associated with clinical immune tolerance in antigen-induced T cells, basophils, and antibodies in subjects undergoing oral immunotherapy (OIT) for peanut allergy.
METHODS: In a phase 1 single-site study, we studied participants (n = 23) undergoing peanut OIT and compared them with age-matched allergic control subjects (n = 20) undergoing standard of care (abstaining from peanut) for 24 months. Participants were operationally defined as clinically immune tolerant (IT) if they had no detectable allergic reactions to a peanut oral food challenge after 3 months of therapy withdrawal (IT, n = 7), whereas those who had an allergic reaction were categorized as nontolerant (NT; n = 13).
RESULTS: Antibody and basophil activation measurements did not statistically differentiate between NT versus IT participants. However, T-cell function and demethylation of forkhead box protein 3 (FOXP3) CpG sites in antigen-induced regulatory T cells were significantly different between IT versus NT participants. When IT participants were withdrawn from peanut therapy for an additional 3 months (total of 6 months), only 3 participants remained classified as IT participants, and 4 participants regained sensitivity along with increased methylation of FOXP3 CpG sites in antigen-induced regulatory T cells.
CONCLUSIONS: In summary, modifications at the DNA level of antigen-induced T-cell subsets might be predictive of a state of operationally defined clinical immune tolerance during peanut OIT.
OBJECTIVE: Our overall objective was to study laboratory changes associated with clinical immune tolerance in antigen-induced T cells, basophils, and antibodies in subjects undergoing oral immunotherapy (OIT) for peanut allergy.
METHODS: In a phase 1 single-site study, we studied participants (n = 23) undergoing peanut OIT and compared them with age-matched allergic control subjects (n = 20) undergoing standard of care (abstaining from peanut) for 24 months. Participants were operationally defined as clinically immune tolerant (IT) if they had no detectable allergic reactions to a peanut oral food challenge after 3 months of therapy withdrawal (IT, n = 7), whereas those who had an allergic reaction were categorized as nontolerant (NT; n = 13).
RESULTS: Antibody and basophil activation measurements did not statistically differentiate between NT versus IT participants. However, T-cell function and demethylation of forkhead box protein 3 (FOXP3) CpG sites in antigen-induced regulatory T cells were significantly different between IT versus NT participants. When IT participants were withdrawn from peanut therapy for an additional 3 months (total of 6 months), only 3 participants remained classified as IT participants, and 4 participants regained sensitivity along with increased methylation of FOXP3 CpG sites in antigen-induced regulatory T cells.
CONCLUSIONS: In summary, modifications at the DNA level of antigen-induced T-cell subsets might be predictive of a state of operationally defined clinical immune tolerance during peanut OIT.
摘要：
背景：临床免疫耐受的机制仍未完全了解。这项研究提供了与操作定义的临床耐受性模型相关的特定免疫机制的证据。
目的：我们的总体目标是研究与抗原诱导的T细胞的临床免疫耐受相关的实验室变化，嗜碱性粒细胞,和接受口服免疫疗法（OIT）治疗花生过敏的受试者的抗体。
方法：在第一阶段单中心研究中，我们研究了接受花生OIT的参与者(n=23),并将他们与接受24个月标准治疗(放弃花生治疗)的年龄匹配的过敏对照组(n=20)进行了比较.如果参与者在停药3个月后对花生口服食物挑战没有可检测到的过敏反应，则在操作上将其定义为临床免疫耐受（IT）（IT，n=7),而那些有过敏反应的人被归类为非耐受（NT;n=13）。
结果：抗体和嗜碱性粒细胞活化测量没有统计学区分NT和IT参与者。然而,T细胞功能和叉头框蛋白3（FOXP3）CpG位点在抗原诱导的调节性T细胞中的去甲基化在IT和NT参与者之间显着不同。当IT参与者退出花生治疗再持续3个月（总共6个月）时，只有3名参与者仍然被归类为IT参与者，4名参与者恢复了敏感性，同时抗原诱导的调节性T细胞中FOXP3CpG位点甲基化增加。
结论：总之，在抗原诱导的T细胞亚群的DNA水平上的修饰可能预示着花生OIT期间可操作地定义的临床免疫耐受状态。
目的：我们的总体目标是研究与抗原诱导的T细胞的临床免疫耐受相关的实验室变化，嗜碱性粒细胞,和接受口服免疫疗法（OIT）治疗花生过敏的受试者的抗体。
方法：在第一阶段单中心研究中，我们研究了接受花生OIT的参与者(n=23),并将他们与接受24个月标准治疗(放弃花生治疗)的年龄匹配的过敏对照组(n=20)进行了比较.如果参与者在停药3个月后对花生口服食物挑战没有可检测到的过敏反应，则在操作上将其定义为临床免疫耐受（IT）（IT，n=7),而那些有过敏反应的人被归类为非耐受（NT;n=13）。
结果：抗体和嗜碱性粒细胞活化测量没有统计学区分NT和IT参与者。然而,T细胞功能和叉头框蛋白3（FOXP3）CpG位点在抗原诱导的调节性T细胞中的去甲基化在IT和NT参与者之间显着不同。当IT参与者退出花生治疗再持续3个月（总共6个月）时，只有3名参与者仍然被归类为IT参与者，4名参与者恢复了敏感性，同时抗原诱导的调节性T细胞中FOXP3CpG位点甲基化增加。
结论：总之，在抗原诱导的T细胞亚群的DNA水平上的修饰可能预示着花生OIT期间可操作地定义的临床免疫耐受状态。
