A BOVINE ALBUMIN PEPTIDE AS A POSSIBLE TRIGGER OF INSULIN-DEPENDENT DIABETES-MELLITUS
A BOVINE ALBUMIN PEPTIDE AS A POSSIBLE TRIGGER OF INSULIN-DEPENDENT DIABETES-MELLITUS
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DOI：
10.1056/nejm199207303270502
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发表时间：
1992-07-30
影响因子：
158.5
通讯作者：
DOSCH, HM
中科院分区：
文献类型：
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作者：
KARJALAINEN, J;MARTIN, JM;DOSCH, HM
背景。牛奶可能引发自身免疫反应，破坏遗传易感宿主的胰腺细胞，从而导致糖尿病。动物实验表明，牛血清白蛋白（BSA）是乳蛋白，含有17个氨基酸的白蛋白肽（ABBOS）可能是反应性表位。这种肽的抗体与p69反应，p69是一种β细胞表面蛋白，可能代表牛奶诱导的β细胞特异性免疫的靶抗原。我们采用免疫分析法和Western blot分析了142例胰岛素依赖型糖尿病儿童、79例健康儿童和300例成人献血者血清中的抗bsa抗体。对44例糖尿病患者在诊断时、3 ~ 4个月后和1 ~ 2年后进行抗abbos抗体检测。所有糖尿病患者血清中抗bsa抗体IgG浓度升高（但其他乳蛋白抗体未见升高），其中大部分为ABBOS特异性抗体。平均（+/-SE）浓度为每微升8.5+/-0.2千荧光单位（kfU），而健康儿童为每微升1.3+/-0.1千荧光单位。IgA抗体也升高，但IgM抗体没有升高。抗体浓度在诊断后下降，大多数患者在一至两年内达到正常水平。最初的下降几乎完全与抗abbos特异性抗体有关。379名对照者血清中抗bsa抗体浓度较低，但只有2.5%的人有少量abbos特异性igg。胰岛素依赖型糖尿病患者对牛奶白蛋白有免疫力，对一种能够与细胞特异性表面蛋白发生反应的白蛋白肽产生抗体。这些抗体可能参与胰岛功能障碍的发展。
Background. Cow's milk has been implicated as a possible trigger of the autoimmune response that destroys pancreatic beta cells in genetically susceptible hosts, thus causing diabetes mellitus. Studies in animals have suggested that bovine serum albumin (BSA) is the milk protein responsible, and an albumin peptide containing 17 amino acids (ABBOS) may be the reactive epitope. Antibodies to this peptide react with p69, a beta-cell surface protein that may represent the target antigen for milk-induced beta-cell-specific immunity.Methods. We used immunoassays and Western blot analysis to analyze anti-BSA antibodies in the serum of 142 children with insulin-dependent diabetes mellitus, 79 healthy children, and 300 adult blood donors. Anti-ABBOS antibodies were measured in 44 diabetic patients at the time of diagnosis, three to four months later, and one to two years later.Results. All the diabetic patients had elevated serum concentrations of IgG anti-BSA antibodies (but not of antibodies to other milk proteins), the bulk of which were specific for ABBOS. The mean (+/-SE) concentration was 8.5+/-0.2 kilofluorescence units (kfU) per microliter, as compared with 1.3+/-0.1 kfU per microliter in the healthy children. IgA antibodies were elevated as well, but not IgM antibodies. The antibody concentrations declined after diagnosis, reaching normal levels in most patients within one to two years. The initial decline involved anti-ABBOS-specific antibodies almost exclusively. Much lower serum concentrations of anti-BSA antibodies were found in all 379 control subjects, but only 2.5 percent of them had small amounts of ABBOS-specific IgG.Conclusions. Patients with insulin-dependent diabetes mellitus have immunity to cow's-milk albumin, with antibodies to an albumin peptide that are capable of reacting with a beta-cell-specific surface protein. Such antibodies could participate in the development of islet dysfunction.