Abstract
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.
Highlights
The humoral immune system is a highly evolved network of biomolecules that captures information about environmental exposure
Is there a typical “healthy” immunosignature? Is a healthy immunosignature stable over time? How much variance exists between healthy individuals? How do infection and vaccine signatures differ? We created a number of experiments using human volunteers to address these questions
Disease Monitoring—One of the major impediments to any new diagnostic is the ability to cope with variations in large cohorts of nondisease patients [6]
Summary
The humoral immune system is a highly evolved network of biomolecules that captures information about environmental exposure. The fact that the same molecule both captures information and exerts an effect has consequences on vaccine development and disease diagnosis [1]. An immunosignature provides a snapshot of many antibodies simultaneously. It has become clear that healthy controls play an important role in the ability to detect disease patterns. Rather than measuring a single biomarker, immunosignatures measure hundreds of informative markers, yielding a reproducible and predictable diseasespecific pattern with sufficient capacity to encompass variations in the normal population. Antibodies may solve many of these issues They are amplified during affinity maturation; they are stable, abundant, and can be detected using anticlass and antispecies antibodies. Immunosignatures measure many antibodies simultaneously, which enhances specificity. Analysis can be very basic, with statistical methods used to select features and probabilistic classifiers for class prediction [14]
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