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The ubiquitous presence of serum autoantibodies and their utility as diagnostic biomarkers of disease

by
Min Han
M.D., 2008
Xi`an Jiaotong University, China

Thesis Advisor: Robert Nagele, Ph.D.

Cell and Molecular Biology Program

Science Center, Room 290

Friday, October 12, 2012
12 pm


Abstract

Conventionally, autoantibodies are considered to be a consequence of compromised self-tolerance, which is mostly, if not always, linked to autoimmune diseases. In this study, I used multiple techniques to detect antibodies that react to self-antigens without the limitation of known autoimmune diseases or known autoantigens. Results showed that autoantibodies are both abundant and ubiquitous in human serum. Western blot analysis revealed that they are also abundantin swine and rat serum and that individual autoantibody profiles appear to be stable over long time periods. Thousands of self-reactive antibodies were detected in individual human serum (n = 166) regardless of age, gender and health status, using 9,400 native proteins on human protein microarrays as potential targets. Comparing the autoantibody profiles of Alzheimerís disease (AD) patients and Parkinsonís disease (PD) patients with those of age- and gender- matched controls, I discovered separate panels of autoantibodies that can diagnose AD and PD with over 90% accuracy. Studies to verify these findings with larger sets of serum samples representing the population are currently underway. These findings have prompted us to propose that autoantibodies may have an important, but as yet unrecognized, physiological function. One possibility is that they help in the clearance of cell and tissue debris generated on a day-to-day basis in both healthy and diseased individuals. If true, when disease is ongoing in an individual, larger amounts of cell and tissue-specific debris are expected to be generated which lead to a corresponding increase in the production of autoantibodies responsible for clearing those debris. Therefore, identification of disease-specific autoantibodies may not only benefit disease diagnostics, but also opens a new door for us to investigate the immunology of many diseases. For all of these studies, I characterized the human protein microarray, which is a new quantitative, high-throughput platform for immune response profiling. I also worked out a stringent strategy for protein array data analysis. Taken together, my work shows that the approach of employing protein microarrays and bioinformatics algorithms to identify serum autoantibody patterns can be applied to biomarker discovery for many diseases, including neurological disorders, cancer, inflammatory diseases and autoimmune diseases.


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