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1型糖尿病家庭中出生的婴儿经胎盘获得的疾病相关抗体的产后清除。芬兰TRIGR研究小组。降低遗传易患糖尿病风险的试验。

Postnatal elimination of transplacentally acquired disease-associated antibodies in infants born to families with type 1 diabetes. The Finnish TRIGR Study Group. Trial to Reduce IDDM in the Genetically at Risk.

作者信息

Hämäläinen A M, Ronkainen M S, Akerblom H K, Knip M

机构信息

Department of Pediatrics, University of Oulu, Finland.

出版信息

J Clin Endocrinol Metab. 2000 Nov;85(11):4249-53. doi: 10.1210/jcem.85.11.6987.

Abstract

The elimination of maternally acquired, diabetes-associated antibodies from the peripheral circulation of infants was studied in a population of 47 mothers and their newborn infants from families in which at least 1 first degree relative had type 1 diabetes. Blood samples were taken from the placental cord; from the infant at follow-up visits at the ages of 3, 6, 9, 12, 18, and 24 months; and from the mother at the time of delivery. The samples were analyzed for cytoplasmic islet cell antibodies (ICA), insulin antibodies (IA), autoantibodies to the 65-kDa isoform of glutamic acid decarboxylase (GADA), and autoantibodies to the protein tyrosine phosphatase-related IA-2 antigen (IA-2A). The mean elimination times for ICA, IA, GADA, and IA-2A were 3.1, 3.1, 4.5, and 4.3 months (P = NS), respectively. The initial levels of IA, GADA, and IA-2A in the cord blood correlated closely with the elimination time (r(s) = 0:84-0.91; P < 0.001). The mean proportions of ICA, IA, GADA, and IA-2A still detectable were 18%, 21%, 30%, and 20%, respectively, at 3 months; 2.2%, 14%, 10%, and 6% at 6 months; and 0.3%, 15%, 2.3%, and 5.1% at 9 months. One infant still tested positive for GADA at the age of 12 months, whereas all of the other antibodies had been eliminated by that age. When observing the natural history of beta-cell autoimmunity or when screening for secondary prevention in young children, cross-sectional autoantibody analyses do not provide sufficient information. Repeated testing is to be recommended in young children. In infancy, increasing antibody levels most likely reflect de novo synthesis of diabetes-associated autoantibodies.

摘要

在一个由47位母亲及其新生儿组成的群体中,研究了从婴儿外周循环中清除母体获得的糖尿病相关抗体的情况。这些家庭中至少有1名一级亲属患有1型糖尿病。在胎盘脐带处采集血样;在婴儿3、6、9、12、18和24个月大进行随访时采集血样;并在分娩时采集母亲的血样。对样本进行细胞质胰岛细胞抗体(ICA)、胰岛素抗体(IA)、针对65 kDa谷氨酸脱羧酶同工型的自身抗体(GADA)以及针对蛋白酪氨酸磷酸酶相关IA-2抗原的自身抗体(IA-2A)的分析。ICA、IA、GADA和IA-2A的平均清除时间分别为3.1、3.1、4.5和4.3个月(P = 无显著差异)。脐带血中IA、GADA和IA-2A的初始水平与清除时间密切相关(r(s) = 0.84 - 0.91;P < 0.001)。在3个月时,仍可检测到的ICA、IA、GADA和IA-2A的平均比例分别为18%、21%、30%和20%;在6个月时分别为2.2%、14%、10%和6%;在9个月时分别为0.3%、15%、2.3%和5.1%。1名婴儿在12个月大时GADA检测仍为阳性,而其他所有抗体在该年龄时均已清除。在观察β细胞自身免疫的自然病程或对幼儿进行二级预防筛查时,横断面自身抗体分析无法提供足够的信息。建议对幼儿进行重复检测。在婴儿期,抗体水平升高最有可能反映糖尿病相关自身抗体的重新合成。

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