Suprun Maria, Getts Robert, Grishina Galina, Tsuang Angela, Suárez-Fariñas Mayte, Sampson Hugh A
Icahn School of Medicine at Mount Sinai, New Yok, NY, USA.
AllerGenis LLC, Hatfield, PA, USA.
Allergy. 2020 Oct;75(10):2633-2643. doi: 10.1111/all.14357. Epub 2020 Jun 1.
Egg-white ovomucoid, that is, Gal d 1, is associated with IgE-mediated allergic reactions in most egg-allergic children. Epitope-specific IgE levels have been correlated with the severity of egg allergy, while emerging evidence suggests that other antibody isotypes (IgG , IgG , IgA, and IgD) may have a protective function; yet, their epitope-specific repertoires and associations with atopic comorbidities have not been studied.
Bead-based epitope assay (BBEA) was used to quantitate the levels of epitope-specific (es)IgA, esIgE, esIgD, esIgG , and esIgG antibodies directed at 58 (15-mer) overlapping peptides, covering the entire sequence of ovomucoid, in plasma of 38 egg-allergic and 6 atopic children. Intraclass correlation (ICC) and coefficient of variation (CV) were used for the reliability assessment. The relationships across esIgs were evaluated using network analysis; linear and logistic regressions were used to compare groups based on egg allergy status and comorbidities.
BBEA had high reliability (ICC >0.75) and low variability (CV <20%) and could detect known IgE-binding epitopes. Egg-allergic children had lower esIgA (P = .010) and esIgG (P = .016) and higher esIgE (P < .001) and esIgD (P = .015) levels compared to the atopic controls. Interestingly, within the allergic group, children with higher esIgD had decreased odds of anaphylactic reactions (OR =0.48, P = .038). Network analysis identified most associations between esIgE with either esIgG or esIgD; indicating that IgE-secreting plasma cells could originate from either sequential isotype switch from antigen-experienced intermediate isotypes or directly from the IgD B cells.
Collectively, these data point toward a contribution of epitope-specific antibody repertoires to the pathogenesis of egg allergy.
蛋清类卵黏蛋白,即Gal d 1,与大多数鸡蛋过敏儿童的IgE介导的过敏反应相关。表位特异性IgE水平与鸡蛋过敏的严重程度相关,而新出现的证据表明,其他抗体同种型(IgG、IgG、IgA和IgD)可能具有保护作用;然而,它们的表位特异性库以及与特应性合并症的关联尚未得到研究。
采用基于微珠的表位分析(BBEA)定量检测38名鸡蛋过敏儿童和6名特应性儿童血浆中针对58个(15肽段)重叠肽段(覆盖类卵黏蛋白的整个序列)的表位特异性(es)IgA、esIgE、esIgD、esIgG和esIgG抗体水平。组内相关系数(ICC)和变异系数(CV)用于可靠性评估。使用网络分析评估esIgs之间的关系;使用线性回归和逻辑回归根据鸡蛋过敏状态和合并症比较各组。
BBEA具有高可靠性(ICC>0.75)和低变异性(CV<20%),并且能够检测已知的IgE结合表位。与特应性对照相比,鸡蛋过敏儿童的esIgA(P = 0.010)和esIgG(P = 0.016)水平较低,而esIgE(P < 0.001)和esIgD(P = 0.015)水平较高。有趣的是,在过敏组中,esIgD水平较高的儿童发生过敏反应的几率降低(OR = 0.48,P = 0.038)。网络分析确定了esIgE与esIgG或esIgD之间的大多数关联;表明分泌IgE的浆细胞可能源自抗原经历的中间同种型的顺序同种型转换,或直接源自IgD B细胞。
总体而言,这些数据表明表位特异性抗体库对鸡蛋过敏的发病机制有影响。