Rowe Julie, Kusel Merci, Holt Barbara J, Suriyaarachchi Devinda, Serralha Michael, Hollams Elysia, Yerkovich Stephanie T, Subrata Lily S, Ladyman Claire, Sadowska Agata, Gillett Jamie, Fisher Elizabeth, Loh Richard, Soderstrom Lars, Ahlstedt Staffan, Sly Peter D, Holt Patrick G
Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia.
J Allergy Clin Immunol. 2007 May;119(5):1164-73. doi: 10.1016/j.jaci.2007.02.016. Epub 2007 Apr 6.
The timing of allergen sensitization is controversial, with conflicting evidence suggesting transplacental priming versus exclusively postnatal priming. Resolution of this question is important in relation to rational design of allergy prevention strategies, particularly the issue of allergen avoidance during pregnancy.
To elucidate the kinetics of sensitization in high-risk children during their first 2 years of life.
We prospectively studied house dust mite (HDM)-specific IgE and IgG(4) antibody production and associated T-cell immunity in a cohort of 200 high-risk infants. Parallel antibody studies tracked responses against a broader panel of inhalant and dietary allergens including peanut.
HDM-induced T(H)2 responses in PBMC from 6 months onward, particularly IL-4 and IL-5, correlated increasingly strongly with sensitization outcomes at 2 years, and a contrasting negative relationship was observed with IFN-gamma response capacity. HDM-induced T-cell responses in cord blood, although common, were unrelated to subsequent sensitization. Transient HDM-IgE (and IgG(4)) production frequently peaked at 6 or 12 months before returning to baseline, which suggests the onset of protective tolerance. This finding contrasted with progressively increasing HDM-IgE titers in children sensitized by 2 years of age. Comparably contrasting patterns were observed in peanut-specific responses in sensitized versus nonsensitized children.
Priming of T(H)2 responses associated with persistent HDM-IgE production occurs entirely postnatally, as HDM reactivity in cord blood seems nonspecific and is unrelated to subsequent development of allergen-specific T(H)2 memory or IgE.
These findings question the scientific basis for existing recommendations for allergen avoidance by high-risk women during pregnancy.
变应原致敏的时机存在争议，相互矛盾的证据表明存在经胎盘启动与仅产后启动两种情况。解决这个问题对于合理设计过敏预防策略很重要，尤其是孕期避免接触变应原这一问题。
阐明高危儿童出生后头两年的致敏动力学。
我们前瞻性地研究了200名高危婴儿队列中针对屋尘螨（HDM）的特异性IgE和IgG4抗体产生情况以及相关的T细胞免疫。平行抗体研究追踪了针对更广泛的吸入性和食物性变应原（包括花生）的反应。
从6个月起，HDM诱导的外周血单核细胞（PBMC）中的Th2反应，特别是IL-4和IL-5，与2岁时的致敏结果相关性越来越强，并且观察到与IFN-γ反应能力呈相反的负相关。HDM诱导的脐带血T细胞反应虽然常见，但与随后的致敏无关。短暂的HDM-IgE（和IgG4）产生通常在6或12个月时达到峰值，然后恢复到基线，这表明保护性耐受的开始。这一发现与2岁时致敏儿童中HDM-IgE滴度逐渐增加形成对比。在致敏与未致敏儿童的花生特异性反应中也观察到了类似的对比模式。
与持续性HDM-IgE产生相关的Th2反应启动完全发生在出生后，因为脐带血中的HDM反应性似乎是非特异性的，并且与变应原特异性Th2记忆或IgE的后续发展无关。
这些发现质疑了现有关于高危女性孕期避免接触变应原建议的科学依据。
