Department of Pediatrics, Division of Allergy and Immunology, UNC School of Medicine, Chapel Hill, NC; UNC Food Allergy Initiative, Department of Pediatrics, UNC School of Medicine, Chapel Hill, NC.
Immune Tolerance Network, Bethesda, Md.
J Allergy Clin Immunol Pract. 2022 Dec;10(12):3270-3275. doi: 10.1016/j.jaip.2022.07.030. Epub 2022 Aug 6.
Antigen-specific immunoglobulin responses have yet to be studied at the oral mucosal surface during peanut oral immunotherapy (PnOIT).
We aimed to quantify salivary peanut-specific IgG4 (PNsIgG4) and IgA (PNsIgA) and total IgG4 and IgA in participants from the Immune Tolerance Network's IMPACT study, a phase 2 PnOIT trial.
Peanut-allergic children, aged 12 months to younger than 48 months at screening, were enrolled and randomized to PnOIT or placebo oral immunotherapy (OIT) for 134 weeks. Per-protocol analysis included 69 PnOIT and 23 placebo participants. Double-blind, placebo-controlled food challenges were conducted at weeks 134 and 160 to assess desensitization and remission, respectively. Saliva samples were collected at baseline and 30, 82, 134, and 160 weeks to quantify PNsIgG4, PNsIgA, and total IgG4 and IgA.
Participants who received PnOIT experienced significant increases in PNsIgG4 in saliva, whereas participants on placebo did not (P < .01 at all time points). The PNsIgA/total IgA ratio was also significantly increased in participants treated with PnOIT when compared with those receiving placebo at 30 and 82 weeks (P < .05). During PnOIT, desensitized participants had increased PNsIgA that plateaued, whereas the not desensitized/no remission group did not change over time. Interestingly, when the PnOIT group was evaluated by clinical outcome, PNsIgA was higher at baseline in the not desensitized/no remission group than in the desensitized/remission group (P < .05).
PnOIT induces substantial increases in allergen-specific IgG4 and IgA in saliva. These data provide insight into OIT-induced mucosal responses and suggest the utility of these easily obtained samples for biomarker development.
在花生口服免疫治疗(PnOIT)期间,口腔黏膜表面的抗原特异性免疫球蛋白反应尚未得到研究。
我们旨在量化免疫耐受网络 IMPACT 研究中参与者的唾液花生特异性 IgG4(PNsIgG4)和 IgA(PNsIgA)以及总 IgG4 和 IgA,这是一项 2 期 PnOIT 试验。
在筛选时年龄为 12 个月至 48 个月以下的花生过敏儿童被招募并随机分配接受 PnOIT 或安慰剂口服免疫治疗(OIT)134 周。按方案分析包括 69 名 PnOIT 和 23 名安慰剂参与者。在第 134 周和第 160 周进行双盲、安慰剂对照的食物挑战,以分别评估脱敏和缓解。在基线和第 30、82、134 和 160 周采集唾液样本以量化 PNsIgG4、PNsIgA 和总 IgG4 和 IgA。
接受 PnOIT 的参与者的唾液 PNsIgG4 显著增加,而接受安慰剂的参与者则没有(所有时间点均<.01)。与接受安慰剂的参与者相比,接受 PnOIT 治疗的参与者的 PNsIgA/总 IgA 比值在第 30 和 82 周也显著增加(P<.05)。在 PnOIT 期间,脱敏参与者的 PNsIgA 增加并趋于稳定,而未脱敏/无缓解组随时间变化未改变。有趣的是,当根据临床结果评估 PnOIT 组时,未脱敏/无缓解组的 PNsIgA 在基线时高于脱敏/缓解组(P<.05)。
PnOIT 诱导唾液中过敏原特异性 IgG4 和 IgA 的大量增加。这些数据提供了对 OIT 诱导的黏膜反应的深入了解,并表明这些容易获得的样本可用于生物标志物的开发。