Norwegian Institute of Public Health, Oslo, Norway.
Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, UK.
Pediatr Diabetes. 2019 Sep;20(6):728-735. doi: 10.1111/pedi.12875. Epub 2019 Jun 19.
Maternal microchimerism (MMc), the transmission of small quantities of maternal cells to the fetus, is relatively common and persistent. MMc has been detected with increased frequency in the circulation and pancreas of type 1 diabetes (T1D) patients. We investigated for the first time whether MMc levels at birth predict future T1D risk. We also tested whether cord blood MMc predicted MMc in samples taken at T1D diagnosis.
Participants in the Norwegian Mother and Child Cohort study were human leukocyte antigen (HLA) class II typed to determine non-inherited, non-shared maternal alleles (NIMA). Droplet digital (dd) polymerase chain reaction (PCR) assays specific for common HLA class II NIMA (HLADQB1*03:01, *04:02, and *06:02/03) were developed and validated. MMc was estimated as maternal DNA quantity in the fetal circulation, by NIMA specific ddPCR, measured in cord blood DNA from 71 children who later developed T1D and 126 controls within the cohort.
We found detectable quantities of MMc in 34/71 future T1D cases (48%) and 53/126 controls (42%) (adjusted odds ratio [aOR] 1.27, 95% confidence interval (CI) 0.68-2.36), and no significant difference in ranks of MMc quantities between cases and controls (Mann-Whitney P = .46). There was a possible association in the NIMA HLA-DQB1*03:01 subgroup with later T1D (aOR 3.89, 95%CI 1.05-14.4). MMc in cord blood was not significantly associated with MMc at T1D diagnosis.
Our findings did not support the hypothesis that the degree of MMc in cord blood predict T1D risk. The potential subgroup association with T1D risk should be replicated in a larger cohort.
母体微嵌合体（MMc），即少量母体细胞传递给胎儿，相对较为常见且持续存在。在 1 型糖尿病（T1D）患者的循环和胰腺中，已经检测到 MMc 出现频率增加。我们首次研究了出生时的 MMc 水平是否可以预测未来 T1D 风险。我们还测试了脐带血 MMc 是否可以预测 T1D 诊断时的 MMc。
挪威母婴队列研究的参与者进行人类白细胞抗原（HLA）Ⅱ类分型，以确定非遗传、非共享的母体等位基因（NIMA）。开发并验证了针对常见 HLA Ⅱ类 NIMA（HLADQB1*03:01、04:02 和06:02/03）的液滴数字（dd）聚合酶链反应（PCR）检测。通过脐带血 DNA 中的 NIMA 特异性 ddPCR 来估计胎儿循环中的 MMc，该方法测量了 71 名后来发展为 T1D 的儿童和队列中的 126 名对照者的脐带血 DNA 中的 MMc。
我们在 71 例未来 T1D 病例（48%）和 126 例对照者（42%）中发现了可检测到的 MMc 量（校正比值比[aOR]1.27，95%置信区间[CI]0.68-2.36），病例和对照者之间的 MMc 量等级没有显著差异（Mann-Whitney P=0.46）。在 NIMA HLA-DQB1*03:01 亚组中，与后来的 T1D 可能存在关联（aOR 3.89，95%CI 1.05-14.4）。脐带血中的 MMc 与 T1D 诊断时的 MMc 无显著相关性。
我们的研究结果不支持脐带血中 MMc 程度预测 T1D 风险的假说。该潜在的亚组与 T1D 风险的关联应在更大的队列中进行复制。
