Serum Antibody Profiling with a Carbohydrate Microarray

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Biomarkers play a critical role in cancer diagnosis and treatment. Antibodies represent an important class of biomarkers with many advantageous features such as good stability, accessibility in biofluids, and easy detection. There has been extensive research on identifying changes in antibody levels to protein antigens; however, analysis of antibodies that binding carbohydrate antigens have been largely underutilized. Our carbohydrate microarray is well-suited to monitor the repertoire of anti-glycan antibodies in human serum and to study changes in their levels in response to disease or treatment of disease. The high-throughput approach can be used to identify new single biomarkers or to identify combinations of changes or profiles that are useful as biomarkers. We have developed and validated a carbohydrate microarray assay for measuring antibody levels in human serum. We have used the array to characterize the natural collection of antibodies in healthy individuals and to evaluate relationships between covariates and antibody levels. We have found no significant differences based on gender, race, or geographic location. However, statistically significant differences were associated with blood type and age. In addition, we have evaluated changes within individuals over time and found that antibody levels are stable over periods of 3-13 weeks. This information is critical for identifying changes that are beyond the natural level of variation. In collaboration with Dr. Schlom and colleagues, we have been using the array to evaluate immune responses to the PSA-TRICOM prostate cancer vaccine. In addition, we have evaluated responses to keyhole limpet hemocyanin (KLH), an immunotherapeutic agent used to prevent recurrence of bladder cancer after surgery. We have recently started a project with Dr. Marjorie Robert-Guroff to profile immune responses to her HIV/SIV vaccine.