Peanut epitopes for IgE and IgG4 in peanut-sensitized children in relation to severity of peanut allergy

Peanut epitopes for IgE and IgG4 in peanut-sensitized children in relation to severity of peanut allergy
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DOI:
10.1016/j.jaci.2007.11.039
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发表时间:
2008-03-01
影响因子:
14.2
通讯作者:
Shreffler, Wayne G.
Shreffler, Wayne G.
中科院分区:
医学1区
文献类型:
--
作者:
Flinterman, Annebeth E.;Knol, Edward F.;Shreffler, Wayne G.

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背景:更好地了解花生抗体反应与临床敏感性之间的关系可能会带来更准确的预测。目的:我们试图调查花生特异性IgE和IgG4表位多样性与花生过敏儿童挑战定义的临床敏感性的关系。方法:采用双盲、安慰剂对照花生挑战的方法测定24名花生过敏儿童的临床敏感性。包括6名特应性对照受试者。用芯片免疫分析方法分析了花生致敏患者血清与代表重组Ara h1、Ara h2和Ara h3序列的419个重叠的15个氨基酸多肽结合的特异性IgE和IgG4。该患者组与先前报道的相同的arah1、arah2和arah3表位发生反应。IgE表位多样性(即识别的表位数目)与临床敏感性呈正相关(r=0.6),表位多样性最大的患者比表位多样性最低的患者更敏感(P=0.021)。没有特定的表位与花生的严重反应有关。观察到与IgG4结合的表位很相似,但不如IgE结合明显,而且与临床对花生的敏感性无关。在20个月的时间里,IgE和IgG4表位识别模式基本稳定。结论:通过双盲、安慰剂对照花生挑战确定的临床敏感性与更多克隆的IgE应答呈正相关,随着时间的推移保持稳定。
Background: Better understanding of the relationship between antibody response to peanut and clinical sensitivity might lead to more accurate prognostication.Objective: We sought to investigate peanut-specific IgE and IgG4 epitope diversity in relation to challenge-defined clinical sensitivity to peanut in a group of peanut-sensitized children.Methods: Clinical sensitivity was determined by means of double-blind, placebo-controlled peanut challenges in 24 sensitized children. Six atopic control subjects were included. Specific IgE and IgG4 binding to 419 overlapping 15-amino-acid peptides representing the sequence of recombinant Ara h 1, Ara h 2, and Ara h3 was analyzed by means of microarray immunoassay.Results: Peanut-sensitized patient sera bound significantly more IgE and IgG4 epitopes than control sera. This patient group reacted to the same Ara h 1, Ara h 2, and Ara h 3 epitopes as reported previously. There was a positive correlation between IgE epitope diversity (ie, number of epitopes recognized) and clinical sensitivity (r = 0.6), such that patients with the greatest epitope diversity were significantly more sensitive than those with the lowest diversity (P = .021). No specific epitopes were associated with severe reactions to peanut. IgG4 binding was observed to largely similar epitopes but was less pronounced than IgE binding and did not relate to the clinical sensitivity to peanut. IgE and IgG4 epitope-recognition patterns were largely stable over a 20-month period.Conclusion: Clinical sensitivity, as determined by means of double-blind, placebo-controlled peanut challenge, is positively related to a more polyclonal IgE response, which remains stable over time.