Hsiao Kuang-Chih, Ponsonby Anne-Louise, Ashley Sarah, Lee Cassandra Yuen Yan, Jindal Lalita, Tang Mimi L K
Department of Immunology, Starship Children's Hospital, Auckland, New Zealand.
Department of Paediatrics, University of Auckland, Auckland, New Zealand.
Clin Exp Allergy. 2022 Apr 11. doi: 10.1111/cea.14146.
Probiotic and Peanut Oral Immunotherapy (PPOIT) is effective at inducing sustained unresponsiveness (SU) at end-of-treatment and this effect persists up to four years post-treatment, referred to as persistent SU. We sought to evaluate (i) how PPOIT altered peanut-specific humoral immune indices, and (ii) how such longitudinal indices relate to persistent SU.
Longitudinal serum/plasma levels of whole peanut- and peanut component- (Ara-h1, -h2, -h3, -h8, -h9) specific-IgE (sIgE) and specific-IgG4 (sIgG4) antibodies were measured by ImmunoCAP and salivary peanut-specific-IgA (sIgA) by ELISA in children (n=62) enrolled in the PPOIT-001 randomised trial from baseline (T0) to 4-years post-treatment (T5). Multivariate regression analyses of log-transformed values were used for point-in-time between group comparisons. Generalised estimating equations (GEE) were used for longitudinal comparisons between groups.
PPOIT was associated with changes in sIgE and sIgG4 over time. sIgE levels were significantly reduced post-treatment [T5, PPOIT v.s. Placebo ratio of geometric mean (GM): Ara-h1 0.07, p=0.008; Ara-h2 0.08, p=0.007; Ara-h3 0.15, p=0.021]. sIgG4 levels were significantly increased by end-of-treatment (T1, PPOIT v.s. Placebo ratio of GM: Ara-h1 3.77, p=0.011; Ara-h2 17.97, p<0.001; Ara-h3 10.42, p<0.001) but levels in PPOIT group decreased once treatment was stopped and returned to levels comparable with Placebo group by T5. Similarly, salivary peanut sIgA increased during treatment, as early as 4 months of treatment (PPOIT v.s. Placebo, ratio of GM: 2.04, p=0.014), then reduced post-treatment.
PPOIT was associated with broad reduction in peanut specific humoral responses which may mediate the clinical effects of SU that persists to 4-years post-treatment.
益生菌与花生口服免疫疗法（PPOIT）在治疗结束时能有效诱导持续无反应性（SU），且这种效果在治疗后持续长达四年，称为持续性SU。我们试图评估（i）PPOIT如何改变花生特异性体液免疫指标，以及（ii）这些纵向指标与持续性SU的关系。
在PPOIT - 001随机试验中纳入的62名儿童中，通过免疫化学发光法测量从基线（T0）到治疗后4年（T5）期间纵向血清/血浆中全花生和花生成分（Ara - h1、- h2、- h3、- h8、- h9）特异性IgE（sIgE）和特异性IgG4（sIgG4）抗体水平，通过酶联免疫吸附测定法测量唾液中花生特异性IgA（sIgA）水平。对对数转换值进行多变量回归分析用于组间时间点比较。广义估计方程（GEE）用于组间纵向比较。
PPOIT与sIgE和sIgG4随时间的变化相关。治疗后sIgE水平显著降低 [T5，PPOIT与安慰剂几何均值（GM）比值：Ara - h1为0.07，p = 0.008；Ara - h2为0.08，p = 0.007；Ara - h3为0.15，p = 0.021]。治疗结束时（T1）sIgG4水平显著升高（PPOIT与安慰剂GM比值：Ara - h1为3.77，p = 0.011；Ara - h2为17.97，p < 0.001；Ara - h3为10.42，p < 0.001），但PPOIT组水平在治疗停止后下降，到T5时恢复到与安慰剂组相当的水平。同样，唾液花生sIgA在治疗期间增加，早在治疗4个月时（PPOIT与安慰剂，GM比值：2.04，p = 0.014），然后在治疗后降低。
PPOIT与花生特异性体液反应广泛降低相关，这可能介导了持续至治疗后4年的SU的临床效果。
