Enhanced diagnostic assessment in lupus using differential scanning calorimetry

使用差示扫描量热法增强狼疮诊断评估

• 批准号: 9924439
• 负责人: Nichola C. Garbett
• 金额: $ 34.76万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-05 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9924439
• 关键词: Address; Affect; Albumins; Amyotrophic Lateral Sclerosis; Antibodies; Attention; Autoantibodies; Autoimmune Diseases; Autoimmune Process; Biochemical; Biological; Biological Markers; Characteristics; Classification; Clinical; Clinical Trials; Cross-Sectional Studies; Data; Degenerative polyarthritis; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Differential Scanning Calorimetry; Disease; Disease remission; Early Diagnosis; Emerging Technologies; Goals; Immunologics; Insulin-Dependent Diabetes Mellitus; Investments; Laboratories; Laboratory Study; Lead; Liquid substance; Lupus; Lyme Disease; Malignant neoplasm of cervix uteri; Malignant neoplasm of lung; Mass Spectrum Analysis; Medical Technology; Molecular; Monitor; Organ; Pathology; Patient Monitoring; Patients; Performance; Plasma; Post-Translational Protein Processing; Process; Property; Protein Denaturation; Proteome; Recording of previous events; Rheumatoid Arthritis; Sampling; Sensitivity and Specificity; Serologic tests; Serological; Severity of illness; Source; Structure; Systemic Lupus Erythematosus; Technology; Testing; Therapeutic Intervention; Thermodynamics; Urine; base; comorbidity; diagnostic accuracy; diagnostic assay; diagnostic biomarker; effective therapy; human disease; improved; infancy; melanoma; novel diagnostics; novel marker; outcome forecast; personalized medicine; serological marker; targeted treatment; therapy development; tool; treatment response

PROJECT SUMMARY Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease which is particularly difficult to diagnose because of highly diverse clinical manifestations. Current diagnosis is based on clinical history, physical exam and laboratory studies including serological markers. Despite much effort, the development of improved diagnostic approaches is still in its infancy and has yet to have a clinical impact. Therefore, there is a substantial unmet clinical need for an investment in improving the diagnostic arsenal, particularly approaches that would lead to enhanced diagnostic accuracy of SLE, differentiation of SLE from other autoimmune classes and would provide information concerning disease activity and pathobiology for development of targeted and personalized therapies. We have recently demonstrated the use of differential scanning calorimetry (DSC) as a new diagnostic approach for the analysis of blood plasma samples for the characterization of human diseases. Our data has shown that changes in thermodynamic properties of the high abundance plasma proteome detected by DSC correlate with disease status and therapeutic response in a number of disease settings, including cervical cancer, lung cancer, melanoma, amyotrophic lateral sclerosis, type 1 diabetes, Lyme disease and SLE. We have collected preliminary data on SLE patient samples that have revealed significant differences in thermograms between SLE patients and controls. Comparison of results using DSC profiles (or thermograms) to standard clinical antibody tests revealed significant improvements in sensitivity and overall accuracy with the inclusion of thermogram data. The long term goal of this proposal is to address a critical barrier to early diagnosis thus facilitating effective treatment of SLE patients by developing thermograms as a diagnostic technology. To this end, we will determine the sensitivity of thermograms to multiple SLE clinical and serological factors, disease severity and activity, as well as determine the ability of thermograms to distinguish SLE from other autoimmune and related comorbidities. In addition, we will determine the correlation of thermograms to changes in disease activity, organ involvement and therapeutic intervention during the longitudinal assessment of SLE patients. Finally, we will apply mass spectrometry approaches to interrogate the proteome of SLE patient plasma samples to dissect the biochemical mechanisms by which thermogram modulation occurs in SLE to reveal new biologic information for diagnostic application in SLE. The data gained from this proposal will determine the utility of thermograms for enhanced diagnostic assessment and monitoring of SLE patients and, additionally, could identify new biomarkers associated with SLE pathobiology which could improve our understanding of the disease process and lead to the development of more specific diagnostic tests.

项目摘要 全身性红斑狼疮（SLE）是一种原型自身免疫性疾病，尤其难以 由于临床表现高度多样化，因此诊断。当前的诊断是基于临床病史的 体格检查和实验室研究，包括血清学标记。尽管付出了很多努力，但 改进的诊断方法仍处于起步阶段，尚未产生临床影响。因此，有一个 对改善诊断库的投资的巨大未满足的临床需求，尤其是方法 这将导致SLE的诊断准确性提高，SLE与其他自身免疫类别的分化 并将提供有关疾病活动和病理生物学的信息，以开发目标和 个性化疗法。我们最近证明了使用差扫描量热法（DSC）作为一个 用于分析血浆样本的新诊断方法，以表征人类疾病。 我们的数据表明，高丰度等离子体蛋白质组的热力学特性的变化 通过DSC检测到许多疾病环境中的疾病状况和治疗反应， 包括宫颈癌，肺癌，黑色素瘤，肌萎缩性外侧硬化症，1型糖尿病，莱姆病 和SLE。我们已经收集了有关SLE患者样品的初步数据，这些数据显示出明显的 SLE患者和对照组之间的热图差异。使用DSC概况比较结果（或 对标准临床抗体测试的热图）表明，灵敏度和总体上有显着提高 包含热合数据的精度。该提议的长期目标是解决关键 早期诊断的障碍，从而促进了通过将热图作为A的有效治疗 诊断技术。为此，我们将确定热图对多个SLE临床的敏感性 以及血清学因素，疾病的严重程度和活动，并确定热图的能力 将SLE与其他自身免疫性和相关合并症区分开。此外，我们将确定 热图与疾病活动，器官受累和治疗干预的变化的相关性 在对SLE患者的纵向评估期间。最后，我们将采用质谱法 询问SLE患者血浆样品的蛋白质组，以剖析生化机制 在SLE中发生热合图调制，以揭示新的生物学信息，以用于SLE中的诊断应用。 从该提案中获得的数据将确定热能图的实用性，以增强诊断 对SLE患者的评估和监测，此外，可以识别与 SLE病理生物学可以改善我们对疾病过程的理解并导致发展 更具体的诊断测试。