Atchley D H, Lopes-Virella M F, Zheng D, Kenny D, Virella G
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Diabetologia. 2002 Nov;45(11):1562-71. doi: 10.1007/s00125-002-0962-y. Epub 2002 Oct 12.
AIMS/HYPOTHESIS: Oxidized LDL is immunogenic and immune complexes formed by oxidized LDL and corresponding antibodies are pro-atherogenic and pro-inflammatory. Considering that macroalbuminuria is a risk factor for coronary heart disease and that common pathogenic factors for atherosclerosis and glomerulosclerosis exist, our aim was to determine whether the amount and/or characteristics of oxidized LDL- anti-oxidized LDL complexes correlated with the degree of albuminuria in patients with Type I (insulin-dependent) diabetes mellitus.
We studied 33 macroalbuminuric patients (albumin excretion rate >300 mg/24 h) and 29 microalbuminuric patients (albumin excretion rate >or=30 mg/24 h and <or=300 mg/24 h) who were matched for age, sex and HbA(1C) concentrations with 43 patients with normal albuminuria. In all patients we isolated and characterized oxidized LDL-anti-oxidized LDL complexes. A subgroup of 47 patients (22 with normal albuminuria, 11 with microalbuminuria, and 14 with macroalbuminuria) was randomly selected from the larger group for characterization of the antibody moiety of oxidized LDL immune complexes.
The concentrations of oxidized LDL immune complexes were increased in patients with macroalbuminuria (total cholesterol in immune complexes isolated from patients with macroalbuminuria was 272+/-20 vs 204+/-18 micro g/ml in patients with normoalbuminuria, p<0.03). Also, the Kd of oxLDL antibodies isolated from the immune complexes was lower in patients with abnormal albuminuria than in patients with normoalbuminuria (0.86+/-0.1x10(-8) vs 1.13+/-0.1x10(-8) mol/l, p<0.05).
CONCLUSION/INTERPRETATION: The data indicate that high concentrations of oxidized LDL-anti-oxidized LDL complexes, particularly when formed with antibodies of higher avidity, are associated with abnormal proteinuria.
目的/假设：氧化型低密度脂蛋白具有免疫原性，由氧化型低密度脂蛋白和相应抗体形成的免疫复合物具有促动脉粥样硬化和促炎作用。鉴于大量蛋白尿是冠心病的危险因素，且动脉粥样硬化和肾小球硬化存在共同的致病因素，我们的目的是确定氧化型低密度脂蛋白-抗氧化型低密度脂蛋白复合物的数量和/或特性是否与Ⅰ型（胰岛素依赖型）糖尿病患者的蛋白尿程度相关。
我们研究了33例大量蛋白尿患者（白蛋白排泄率>300mg/24小时）和29例微量蛋白尿患者（白蛋白排泄率≥30mg/24小时且≤300mg/24小时），他们在年龄、性别和糖化血红蛋白（HbA₁C）浓度方面与43例蛋白尿正常的患者相匹配。我们对所有患者分离并鉴定了氧化型低密度脂蛋白-抗氧化型低密度脂蛋白复合物。从较大的组中随机选取47例患者（22例蛋白尿正常、11例微量蛋白尿、14例大量蛋白尿）的亚组，以鉴定氧化型低密度脂蛋白免疫复合物的抗体部分。
大量蛋白尿患者中氧化型低密度脂蛋白免疫复合物的浓度升高（从大量蛋白尿患者分离的免疫复合物中的总胆固醇为272±20μg/ml，而正常蛋白尿患者为204±18μg/ml，p<0.03）。此外，从免疫复合物中分离的氧化型低密度脂蛋白抗体的解离常数在蛋白尿异常的患者中低于蛋白尿正常的患者（0.86±0.1×10⁻⁸ 与1.13±0.1×10⁻⁸ mol/l，p<0.05）。
结论/解读：数据表明，高浓度的氧化型低密度脂蛋白-抗氧化型低密度脂蛋白复合物，特别是当与高亲和力抗体形成时，与蛋白尿异常有关。
