Naserke H E, Bonifacio E, Ziegler A G
Institute of Diabetes Research, Academic Hospital Schwabing, Kölner Platz 1, D-80804 Munich, Germany.
J Clin Endocrinol Metab. 2001 Oct;86(10):4826-33. doi: 10.1210/jcem.86.10.7931.
Accurate assessment of type 1 diabetes risk in young children requires discrimination between antibodies that are produced by the child and antibodies acquired through the placenta from an islet antibody-positive mother. We studied 682 offspring from mothers with type 1 diabetes and 329 offspring from fathers with type 1 diabetes and nondiabetic mothers for insulin (auto)antibodies, glutamic acid decarboxylase antibodies, and tyrosine phosphatase IA-2 antibodies before age 1 yr and again at age 2 yr to ascertain transience or persistence. Antibodies were detected at age 9 months in 5 (1.5%) offspring from fathers with type 1 diabetes; all were insulin (auto)antibodies only, all persisted and developed multiple antibodies, and 1 developed type 1 diabetes. In contrast, 31 (4.5%) offspring from mothers with type 1 diabetes had antibodies at 9 months; 12 (1.8%) persisted at age 2 yr, and 19 (2.8%) did not persist, suggestive of transient residual maternal antibodies. Multiple antibodies at 9 months were usually persistent (3 of 4 offspring), as were single insulin (auto)antibodies in offspring from mothers with type 1 diabetes (8 of 13 offspring), whereas persistent glutamic acid decarboxylase antibodies (1 of 12) and tyrosine phosphatase IA-2 antibodies (0 of 2) were rare. Offspring with persistent antibodies at age 9 months had a high type 1 diabetes risk (100% by age 5 yr for those with multiple antibodies and 27% for single antibodies at 9 months), whereas offspring with transient antibodies had 0% type 1 diabetes risk (P < 0.01). Transience was associated with very high antibody levels at birth. For insulin (auto)antibodies, the measurement of subclass was also informative. Residual maternal antibody was indicated by similar insulin (auto)antibodies subclasses at 9 months and at birth, whereas different subclasses were indicative of nonmaternal antibody. Moreover, the presence of IgG1-insulin (auto)antibodies was associated with antibody persistence and type 1 diabetes risk. These strategies are helpful in discriminating high and low risk antibodies before age 1 yr and should be important for prognosis and reducing unnecessary parent anxiety.
准确评估幼儿1型糖尿病风险需要区分儿童自身产生的抗体和通过胎盘从胰岛抗体阳性母亲那里获得的抗体。我们研究了682名1型糖尿病母亲的后代以及329名1型糖尿病父亲且母亲无糖尿病的后代，检测他们在1岁前及2岁时的胰岛素（自身）抗体、谷氨酸脱羧酶抗体和酪氨酸磷酸酶IA - 2抗体，以确定这些抗体是短暂存在还是持续存在。在1型糖尿病父亲的后代中，5名（1.5%）在9个月时检测到抗体；所有这些抗体均仅为胰岛素（自身）抗体，全部持续存在并发展为多种抗体，其中1名患1型糖尿病。相比之下，1型糖尿病母亲的后代中有3名（4.5%）在9个月时检测到抗体；12名（1.8%）在2岁时仍有抗体，19名（2.8%）未持续存在，提示为短暂的残留母体抗体。9个月时出现多种抗体通常会持续存在（4名后代中有3名），1型糖尿病母亲后代中的单一胰岛素（自身）抗体也如此（13名后代中有8名），而持续存在的谷氨酸脱羧酶抗体（12名中有1名）和酪氨酸磷酸酶IA - 抗体（2名中有0名）很少见。9个月时抗体持续存在的后代患1型糖尿病风险很高（多种抗体者到5岁时为100%，9个月时单一抗体者为27%）, 而抗体短暂存在的后代患1型糖尿病风险为0%（P<0.01）。抗体短暂存在与出生时抗体水平非常高有关。对于胰岛素（自身）抗体，亚类的检测也具有参考价值。9个月时与出生时胰岛素（自身）抗体亚类相似表明存在残留母体抗体，而不同亚类则表明为非母体抗体。此外，IgG1 - 胰岛素（自身）抗体的存在与抗体持续存在及1型糖尿病风险相关。这些策略有助于在1岁前区分高风险和低风险抗体，对预后及减轻家长不必要的焦虑很重要。
