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 When IT participants were withdrawn from peanut therapy for an additional 3 months (total of 6 months), only 3 participants remained classified as IT participants, and 4 participants regained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.
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。