Vähäsalo P, Petäys T, Knip M, Miettinen A, Saukkonen T, Karjalainen J, Savilahti E, Akerblom H K
Department of Pediatrics, University of Oulu, Finland.
Autoimmunity. 1996;23(3):165-74. doi: 10.3109/08916939608995340.
The relation between islet cell specific antibodies, other autoantibodies and antibodies to cow's milk proteins was studied in IDDM and pre-IDDM by analysing islet cell antibodies (ICA), insulin autoantibodies (IAA), anti-nuclear (ANA), anti-reticulin class IgA [ARA(IgA)], smooth muscle, anti-mitochondria, parietal cell (PCA), adrenal and thyroid antibodies and antibodies to cow's milk formula (CMF), beta-lactoglobulin (BLG) and bovine serum albumin (BSA) in a population based study with more than 650 children with newly diagnosed IDDM and more than 550 initially non-diabetic siblings. After adjustment for age a weak association was seen in the diabetic children between IAA and ANA but none between ICA and autoantibodies directed against the other organ-specific or non-organ-specific antigens. There was no significant difference in cow's milk antibodies between diabetic children with and without ICA or IAA. The siblings with ICA had higher CMF (IgA and IgM) antibody levels and BLG (IgA) antibody levels than the remaining siblings, but no such differences were found when comparing IAA-positive and negative siblings. Siblings positive for ICA had PCA more often than did the ICA-negative siblings, whereas siblings positive for both ICA and PCA had increased levels of antibodies against CMF, BLG and BSA. These findings indicate that the humoral islet cell-associated autoimmunity characteristic of recent-onset childhood IDDM is clearly restricted to the islet cells and not directly related to signs of other organ-specific or non-organ-specific autoimmunity. The observation of increased levels of antibodies to cow's milk proteins in siblings positive for ICA suggests that the immune response to cow's milk proteins may be related to the progressive autoimmune process resulting in beta-cell destruction and ultimately in the clinical manifestation of IDDM. Gastrointestinal autoimmune mechanisms may play a role in the pathogenesis of IDDM, and the association observed between combined ICA and PCA positivity and increased levels of antibodies to cow's milk proteins in the siblings implies that there may be an enhanced transfer of nutritional antigens across the gut barrier in these subjects.
通过分析胰岛细胞抗体（ICA）、胰岛素自身抗体（IAA）、抗核抗体（ANA）、抗网硬蛋白IgA类抗体[ARA（IgA）]、平滑肌抗体、抗线粒体抗体、壁细胞抗体（PCA）、肾上腺抗体、甲状腺抗体以及针对牛奶配方（CMF）、β-乳球蛋白（BLG）和牛血清白蛋白（BSA）的抗体，在一项基于人群的研究中，对650多名新诊断为1型糖尿病（IDDM）的儿童和550多名最初非糖尿病的兄弟姐妹进行了研究，以探讨胰岛细胞特异性抗体、其他自身抗体与牛奶蛋白抗体之间的关系。在对年龄进行校正后，糖尿病儿童中IAA与ANA之间存在微弱关联，但ICA与针对其他器官特异性或非器官特异性抗原的自身抗体之间无关联。有或无ICA或IAA的糖尿病儿童之间，牛奶抗体无显著差异。有ICA的兄弟姐妹的CMF（IgA和IgM）抗体水平和BLG（IgA）抗体水平高于其余兄弟姐妹，但比较IAA阳性和阴性的兄弟姐妹时未发现此类差异。ICA阳性的兄弟姐妹比ICA阴性的兄弟姐妹更常出现PCA，而ICA和PCA均阳性的兄弟姐妹针对CMF、BLG和BSA的抗体水平升高。这些发现表明，近期发病的儿童IDDM的体液胰岛细胞相关自身免疫特征明显局限于胰岛细胞，与其他器官特异性或非器官特异性自身免疫迹象无直接关系。ICA阳性的兄弟姐妹中牛奶蛋白抗体水平升高的观察结果表明，对牛奶蛋白的免疫反应可能与导致β细胞破坏并最终导致IDDM临床表现的进行性自身免疫过程有关。胃肠道自身免疫机制可能在IDDM的发病机制中起作用，在兄弟姐妹中观察到的ICA和PCA联合阳性与牛奶蛋白抗体水平升高之间的关联意味着这些受试者中营养抗原可能通过肠道屏障的转运增强。
