Stafford Phillip, Wrapp Daniel, Johnston Stephen Albert
From the ‡Biodesign Institute, Center for Innovations in Medicine, Arizona State University, Tempe, AZ;
§Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH.
Mol Cell Proteomics. 2016 May;15(5):1610-21. doi: 10.1074/mcp.M115.054601. Epub 2016 Feb 22.
The humoral immune system is network of biological molecules designed to maintain a healthy homeostatic equilibrium. Because antibodies are an abundant and highly specific effector of immunological action, they are also an important reservoir of previous host exposures. Antibodies may play a major role in early detection of host challenge. Unfortunately, few practical methods exist for interpreting the information stored in antibody variable regions. Immunosignatures use a microarray of thousands of random sequence peptides to interrogate antibodies in a broad and unbiased fashion. The pattern of binding between antibody and peptide is reproducible. Once the system has been trained on a disease cohort, blinded samples can be reliably predicted. Although immunosignatures of both chronic and infectious disease have been extensively tested, less has been done to demonstrate how healthy immunosignatures change over time or between individuals. Here, we report the results of a study of immunosignatures of healthy persons over brief (12 h sampled once per hour), intermediate (32 days sampled once per day), and long (5 years sampled once every year) time spans. Using this information, we were also able to detect intentional and unintentional immunological perturbations in the form of a vaccine and an infection, respectively. Our findings suggest that, even with the variability inherent in healthy immunosignatures, a single person's immunosignature will remain constant over time. Over this healthy signature, vaccines and infections create subsignatures that are common across multiple people, even subsuming healthy fluctuations. These findings have implications for disease monitoring and early diagnosis.
体液免疫系统是一个旨在维持健康的稳态平衡的生物分子网络。由于抗体是免疫作用中丰富且高度特异性的效应物，它们也是宿主先前接触情况的重要储存库。抗体可能在宿主受到挑战的早期检测中起主要作用。不幸的是，几乎没有实用的方法来解读储存在抗体可变区中的信息。免疫特征使用数千个随机序列肽的微阵列以广泛且无偏倚的方式询问抗体。抗体与肽之间的结合模式是可重复的。一旦该系统在疾病队列上进行了训练，就可以可靠地预测盲法样本。尽管慢性疾病和传染病的免疫特征都已得到广泛测试，但在证明健康免疫特征如何随时间或个体之间变化方面做得较少。在这里，我们报告了一项关于健康人在短时间（12小时，每小时采样一次）、中期（32天，每天采样一次）和长时间（5年，每年采样一次）跨度内免疫特征的研究结果。利用这些信息，我们还分别检测到了疫苗和感染形式的有意和无意的免疫扰动。我们的研究结果表明，即使健康免疫特征存在固有变异性，一个人的免疫特征随时间仍将保持不变。在这个健康特征之上，疫苗和感染会产生在多个人中常见的子特征，甚至包含健康波动。这些发现对疾病监测和早期诊断具有重要意义。
