Otonkoski T, Roivainen M, Vaarala O, Dinesen B, Leipälä J A, Hovi T, Knip M
Hospital for Children and Adolescents and Haartman Institute, Transplantation Laboratory, University of Helsinki, Finland.
Diabetologia. 2000 Oct;43(10):1235-8. doi: 10.1007/s001250051518.
AIMS/HYPOTHESIS: Neonatal diabetes mellitus is rare, and it has not been associated with beta-cell autoimmunity. Enteroviral infections during pregnancy have been implicated as a risk factor for the later development of Type I (insulin-dependent) diabetes mellitus. We now report of a baby girl who was born severely growth-retarded with neonatal insulin-deficient diabetes, and look for evidence of intrauterine enteroviral infections and beta-cell targeted autoimmunity.
Diabetes-associated autoimmunity was studied by measurement of several types of islet cell reactive autoantibodies. The infant's T-cell responses to insulin and enterovirus antigens were recorded and enterovirus antibodies were measured both from the mother and the child.
Several types of diabetes-associated autoantibodies were detected postnatally, including insulin autoantibodies, conventional islet cell autoantibodies and glutamic acid decarboxylase antibodies, whereas no autoantibodies were observed in the mother. The infant's T-cells showed reactivity to insulin and purified enterovirus particles. Based on serological studies, the pathogenetic process could have been triggered by an echovirus 6 infection during pregnancy. The patient's diabetes has been permanent, although there were signs of endogenous insulin production for several months. Exocrine pancreatic insufficiency was diagnosed at the age of 1 year.
CONCLUSION/INTERPRETATION: These observations suggests that enteroviral infections may induce beta-cell autoimmunity even in utero.
目的/假设:新生儿糖尿病较为罕见,且与β细胞自身免疫无关。孕期肠道病毒感染被认为是I型(胰岛素依赖型)糖尿病后期发病的一个危险因素。我们现报告一名出生时严重生长发育迟缓且患有新生儿胰岛素缺乏性糖尿病的女婴,并寻找宫内肠道病毒感染及β细胞靶向自身免疫的证据。
通过检测几种胰岛细胞反应性自身抗体来研究与糖尿病相关的自身免疫。记录婴儿对胰岛素和肠道病毒抗原的T细胞反应,并检测母亲和婴儿的肠道病毒抗体。
出生后检测到几种与糖尿病相关的自身抗体,包括胰岛素自身抗体、传统胰岛细胞自身抗体和谷氨酸脱羧酶抗体,而母亲体内未观察到自身抗体。婴儿的T细胞对胰岛素和纯化的肠道病毒颗粒有反应。基于血清学研究,致病过程可能是由孕期感染埃可病毒6型引发的。尽管有几个月存在内源性胰岛素分泌迹象,但该患者的糖尿病已呈永久性。1岁时诊断出外分泌性胰腺功能不全。
结论/解读:这些观察结果表明,肠道病毒感染甚至在子宫内就可能诱发β细胞自身免疫。