Koppelman Gerard H, Postma Dirkje S
Beatrix Children's Hospital, University Hospital Groningen, The Netherlands.
Curr Opin Allergy Clin Immunol. 2003 Oct;3(5):347-52. doi: 10.1097/00130832-200310000-00005.
The 'hygiene hypothesis' implies that infections in early childhood prevent the development of atopy. Atopy is caused by the interaction of the environment with genetic factors. Therefore, both contacts with microbial products such as endotoxin as well as CD14, a gene involved in the immunological response to endotoxin, are discussed in this review.
CD14 is a multifunctional receptor for endotoxin and other bacterial wall components. Membrane-bound CD14 is expressed on monocytes and macrophages. It forms a complex with Toll-like receptor 4. Genetic studies have shown an association of variants in the CD14 gene with the prevention of (and severity of) atopy. However, phenotype definitions and the allele that showed association differed between studies. In addition, the presence of endotoxin in house dust appears to be inversely related to atopy in different studies.
It can be hypothesized that different levels of endotoxin exposure could interact with specific CD14 variants in the prevention of atopy. If confirmed in prospective cohort studies, this might represent an important gene by environmental interaction in the development of atopy. This could possibly open ways for the primary prevention of atopy.
“卫生假说”表明儿童早期感染可预防特应性疾病的发生。特应性疾病是由环境与遗传因素相互作用引起的。因此，本综述将讨论与微生物产物如内毒素的接触以及CD14（一种参与对内毒素免疫反应的基因）。
CD14是内毒素和其他细菌细胞壁成分的多功能受体。膜结合型CD14在单核细胞和巨噬细胞上表达。它与Toll样受体4形成复合物。基因研究表明，CD14基因变异与特应性疾病的预防（及严重程度）相关。然而，不同研究中的表型定义和显示相关性的等位基因有所不同。此外，在不同研究中，室内灰尘中内毒素的存在似乎与特应性疾病呈负相关。
可以推测，不同水平的内毒素暴露可能与特定的CD14变异相互作用，从而预防特应性疾病。如果在前瞻性队列研究中得到证实，这可能代表了特应性疾病发生过程中一个重要的基因与环境的相互作用。这可能为特应性疾病的一级预防开辟道路。
