Newkirk M M, LePage K, Niwa T, Rubin L
The Division of Rheumatology, The Montreal General Hospital Research Institute, McGill University, Quebec, Canada.
Cell Mol Biol (Noisy-le-grand). 1998 Nov;44(7):1129-38.
Several tribes of North American Indians are known to have poor glucose control and are at a high risk of developing type 2 diabetes. Similarly some tribes also exhibit RA at a high frequency. We have recently determined that a subset of Caucasian patients with RA mount an immune response to IgG modified with advanced glycation endproducts (AGE). The AGE modifications on IgG in vivo include N(epsilon)-(carboxymethyl) lysine, imidazolone and pentosidine. The presence of IgG-AGE and the antibody response to the IgG-AGE in the Ojibwe tribe of First Nations native Indians where both NIDDM and RA are prevalent was investigated. AGE modified IgG and albumin were determined using a modified nitroblue tetrazolium assay. Rheumatoid factors (RFs) and IgM and IgA anti-IgG-AGE were detected by ELISA. Of the 108 individuals tested, 21 had RA only, 3 had both RA and type 2 diabetes, 30 had type 2 diabetes only and 51 had no diagnosed disease. AGE modified IgG was significantly elevated in the RA group compared to the diabetic group. IgM and IgA RFs were detected in 83% and 50% of the RA patients, compared to 31-37% and 7-10% of the diabetics or normal individuals. IgM anti-IgG-AGE was detected in 54% of the RA patients, in contrast to 7-14% in the diabetics or normal individuals. IgA anti-IgG-AGE was detected in 42% of the RA patients and only 7 to 8% of the NIDDM or normal individuals. The IgM or IgA anti-IgG-AGE antibodies likely contribute to the accumulation of IgG-AGE, possibly through blocked clearance through AGE receptors. A trend towards more severe disease was seen in those Ojibwe RA patients with circulating anti-AGE antibodies. Non-enzymatic glycation may be an important pathogenic link in the RA seen in North American Indians.
已知北美印第安人的几个部落血糖控制不佳，患2型糖尿病的风险很高。同样，一些部落患类风湿性关节炎（RA）的频率也很高。我们最近确定，一部分患有RA的白种人患者会对经晚期糖基化终产物（AGE）修饰的IgG产生免疫反应。体内IgG上的AGE修饰包括N（ε）-（羧甲基）赖氨酸、咪唑啉酮和戊糖苷。我们研究了2型糖尿病（NIDDM）和RA都很普遍的第一民族印第安人奥吉布瓦部落中IgG-AGE的存在情况以及对IgG-AGE的抗体反应。使用改良的硝基蓝四唑试验测定AGE修饰的IgG和白蛋白。通过酶联免疫吸附测定（ELISA）检测类风湿因子（RF）以及IgM和IgA抗IgG-AGE。在接受检测的108人中，21人仅患有RA，3人同时患有RA和2型糖尿病，30人仅患有2型糖尿病，51人未被诊断出患有疾病。与糖尿病组相比，RA组中AGE修饰的IgG显著升高。在83%的RA患者中检测到IgM RF，50%检测到IgA RF，相比之下，糖尿病患者或正常个体中检测到IgM RF的比例为31 - 37%，检测到IgA RF的比例为7 - 10%。在54%的RA患者中检测到IgM抗IgG-AGE，相比之下，糖尿病患者或正常个体中的比例为7 - 14%。在42%的RA患者中检测到IgA抗IgG-AGE，而在NIDDM患者或正常个体中仅为7 - 8%。IgM或IgA抗IgG-AGE抗体可能通过AGE受体阻断清除，从而导致IgG-AGE的积累。在那些有循环抗AGE抗体的奥吉布瓦RA患者中，有疾病更严重的趋势。非酶糖基化可能是北美印第安人所患RA中的一个重要致病环节。
