Yang Na, Wang Linlin, Finnell Richard H, Li Zhiwen, Jin Lei, Zhang Le, Cabrera Robert M, Ye Rongwei, Ren Aiguo
Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, Peking University, Beijing, China.
Dell Pediatric Research Institute, The University of Texas at Austin, Austin, Texas, USA.
Birth Defects Res A Clin Mol Teratol. 2016 Aug;106(8):685-95. doi: 10.1002/bdra.23517. Epub 2016 May 11.
After years of periconceptional folic acid supplementation, the prevalence of neural tube defects (NTDs) remains stable following the remarkable reduction observed immediately after the fortification practice. There is accumulating evidence that folate receptor (FR) autoimmunity may play a role in the etiology of folate-sensitive NTDs.
From 2011 to 2013, 118 NTD cases and 242 healthy controls were recruited from a population-based birth defects surveillance system in Northern China. Enzyme-linked immunosorbent assay was used to measure FR autoantibodies in maternal and cord blood. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI).
Plasma FR autoantibodies levels were significantly elevated in mothers of infants with NTDs compared with mothers of healthy controls. Using the lowest tertile as the referent group, 2.20-fold (95% CI, 0.71-6.80) and 5.53-fold increased odds (95% CI, 1.90-16.08) of NTDs were observed for the second and third tertile of immunoglobulin G (IgG), respectively, and the odds of NTDs for each successive tertile of IgM was 0.98 (95% CI, 0.35-2.75) and 3.49 (95% CI, 1.45-8.39), respectively. A dose-response relationship was found between FR autoantibodies levels and risk of NTDs (P < 0.001 for IgG, P = 0.002 for IgM). The same pattern was observed in both subtypes of spina bifida and anencephaly. No significant difference in levels of cord blood FR autoantibodies was observed.
Higher levels of FR autoimmunity in maternal plasma are associated with elevated risk of NTDs in a dose-response manner. Birth Defects Research (Part A) 106:685-695, 2016. © 2016 Wiley Periodicals, Inc.
经过多年围孕期补充叶酸，神经管缺陷（NTDs）的患病率在强化措施实施后立即显著下降，但之后仍保持稳定。越来越多的证据表明，叶酸受体（FR）自身免疫可能在叶酸敏感型NTDs的病因中起作用。
2011年至2013年，从中国北方一个基于人群的出生缺陷监测系统中招募了118例NTD病例和242例健康对照。采用酶联免疫吸附测定法检测母血和脐血中的FR自身抗体。使用逻辑回归模型估计比值比（OR）和95%置信区间（95%CI）。
与健康对照的母亲相比，NTD患儿母亲血浆中FR自身抗体水平显著升高。以最低三分位数作为参照组，免疫球蛋白G（IgG）第二和第三三分位数的NTDs患病几率分别增加2.20倍（95%CI，0.71 - 6.80）和5.53倍（95%CI，1.90 - 16.08），IgM每连续三分位数的NTDs患病几率分别为0.98（95%CI，0.35 - 2.75）和3.49（95%CI，1.45 - 8.39）。发现FR自身抗体水平与NTDs风险之间存在剂量反应关系（IgG的P < 0.001，IgM的P = 0.002）。脊柱裂和无脑儿的两个亚型均观察到相同模式。脐血FR自身抗体水平未观察到显著差异。
母血中较高水平的FR自身免疫以剂量反应方式与NTDs风险升高相关。《出生缺陷研究（A部分）》106:685 - 695，2016年。©2016威利期刊公司。
