Calorimetric analysis of the plasma proteome: identification of type 1 diabetes patients with early renal function decline.

Calorimetric analysis of the plasma proteome: identification of type 1 diabetes patients with early renal function decline.
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DOI:
10.1016/j.bbagen.2013.05.007
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发表时间:
2013-10
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Klein JB
Klein JB
中科院分区:
其他
文献类型:
--
作者:
Garbett NC;Merchant ML;Chaires JB;Klein JB

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微量白蛋白尿 (MA) 作为 1 型糖尿病 (T1D) 患者进行性肾功能障碍的预测因素受到质疑。因此,需要新的临床终点来识别或预测有早期肾功能衰退(ERFD)风险的患者。最近报道了血浆和其他生物液体的差示扫描量热法 (DSC) 分析的潜在临床实用性。该方法为研究大量血浆蛋白质组中与疾病相关的变化提供了替代的物理基础。应用血浆 DSC 分析来识别参加第 1 型糖尿病微量白蛋白尿自然史乔斯林研究的受试者的独特 ERFD 特征,该研究是一项针对 T1D 患者的前瞻性队列研究。最近的数据表明这些患者血浆肽组的差异与肾功能的纵向测量相关。对表现出 ERFD 的 T1DMA 个体 (n=15) 和匹配的对照受试者 (n=14) 之间 DSC 概况(热像图)特征的差异进行了评估。平均对照组热分析图类似于先前定义的健康热分析图。 ERFD 和对照个体之间存在明显差异。发现主要两个转变的热容量值是患者状态的显着区分因素。这项初步研究的结果表明 DSC 蛋白质组分析对于 T1D 肾脏疾病预后指标的潜在用途。 DSC 显示出对与 T1D 临床状态相关的大量血浆蛋白质组变化的敏感性,为 DSC 分析在临床诊断中的实用性提供了额外的支持。
Microalbuminuria (MA) has been questioned as a predictor of progressive renal dysfunction in patients with type 1 diabetes (T1D). Consequently, new clinical end points are needed that identify or predict patients that are at risk for early renal function decline (ERFD). The potential clinical utility of differential scanning calorimetry (DSC) analysis of blood plasma and other biofluids has recently been reported. This method provides an alternate physical basis with which to study disease-associated changes in the bulk plasma proteome. DSC analysis of blood plasma was applied to identify unique signatures of ERFD in subjects enrolled in the 1st Joslin Study of the Natural History of Microalbuminuria in Type 1 Diabetes, a prospective cohort study of T1D patients. Recent data suggests differences in the plasma peptidome of these patients correlate with longitudinal measures of renal function. Differences in DSC profile (thermogram) features were evaluated between T1D MA individuals exhibiting ERFD (n=15) and matched control subjects (n=14). The average control group thermogram resembled a previously defined healthy thermogram. Differences were evident between ERFD and control individuals. Heat capacity values of the main two transitions were found to be significant discriminators of patient status. Results from this pilot study suggests the potential utility of DSC proteome analysis to prognostic indicators of renal disease in T1D. DSC shows sensitivity to changes in the bulk plasma proteome that correlate with clinical status in T1D providing additional support for the utility of DSC profiling in clinical diagnostics.