Department of Human Genetics, University of Chicago, Chicago, Ill., USA.
J Allergy Clin Immunol. 2013 Jul;132(1):39-44. doi: 10.1016/j.jaci.2012.12.1575. Epub 2013 Feb 21.
Maternal asthma and child's sex are among the most significant and reproducible risk factors for the development of asthma. Although the mechanisms for these effects are unknown, they likely involve nonclassical genetic mechanisms. One such mechanism could involve the transfer and persistence of maternal cells to her offspring, a common occurrence known as maternal microchimerism (MMc). MMc has been associated with many autoimmune diseases but has not been investigated for a role in asthma or allergic disease.
We hypothesized that some of the observed risks for asthma may be due to different rates of transmission or persistence of maternal cells to children of mothers with asthma compared with children of mothers without asthma, or to sons compared with daughters. We further hypothesized that rates of MMc differ between children with and without asthma.
We tested these hypotheses in 317 subjects from 3 independent cohorts by using a real-time quantitative PCR assay to detect a noninherited HLA allele in the child.
MMc was detected in 20.5% of the subjects (range 16.8%-27.1% in the 3 cohorts). We observed lower rates of asthma among MMc-positive subjects than among MMc-negative subjects (odds ratio, 0.38; 95% CI, 0.19-0.79; P = .029). Neither maternal asthma nor sex of the child was a significant predictor of MMc in the child (P = .81 and .15, respectively).
Our results suggest for the first time that MMc may protect against the development of asthma.
母体哮喘和儿童性别是哮喘发展的最重要且可重现的风险因素之一。尽管这些影响的机制尚不清楚，但它们可能涉及非经典的遗传机制。一种这样的机制可能涉及母体细胞向其后代的转移和持续存在，这是一种称为母体微嵌合体（MMc）的常见现象。MMc 与许多自身免疫性疾病有关，但尚未研究其在哮喘或过敏性疾病中的作用。
我们假设，观察到的某些哮喘风险可能是由于哮喘母亲的孩子与非哮喘母亲的孩子相比，或与女儿相比，母体细胞向孩子的传递或持续存在率不同所致。我们进一步假设，患有和不患有哮喘的儿童之间的 MMc 率存在差异。
我们通过使用实时定量 PCR 检测孩子中的非遗传 HLA 等位基因，在来自 3 个独立队列的 317 名受试者中测试了这些假设。
在 20.5%的受试者中检测到 MMc（3 个队列中的范围为 16.8%-27.1%）。与 MMc 阴性受试者相比，MMc 阳性受试者的哮喘发生率较低（比值比，0.38；95%置信区间，0.19-0.79；P=0.029）。母体哮喘或孩子的性别均不是孩子 MMc 的重要预测因素（P=0.81 和 0.15）。
我们的研究结果首次表明，MMc 可能有助于预防哮喘的发生。
