Serum Antibody Profiling with a Carbohydrate Microarray

生物标志物在癌症诊断和治疗中起着关键作用。抗体代表 一类重要的具有许多有利特征如良好稳定性的生物标志物， 在生物液体中的可接近性和容易检测性。有广泛的研究， 识别蛋白抗原抗体水平的变化;然而， 结合性碳水化合物抗原在很大程度上没有得到充分利用。碳水化合物 微阵列非常适合于监测人血清中抗聚糖抗体的所有组成部分 并研究其水平在疾病或疾病治疗中的变化。的 高通量方法可用于鉴定新单一生物标志物或鉴定 这些变化或谱的组合可用作生物标志物。我们已经开发并 验证了用于测量人血清中抗体水平的碳水化合物微阵列测定。我们 已经使用该阵列来表征健康人中抗体的自然集合， 并评估协变量与抗体水平之间的关系。我们有 没有发现基于性别、种族或地理位置的显著差异。然而，在这方面， 统计学上的显著差异与血型和年龄有关。另外我们 已经评估了个体随时间的变化，发现抗体水平是稳定的， 在3-13周的时间内。此信息对于确定 超出了自然的变化水平。与Schlom博士及其同事合作，我们 我一直在使用该阵列来评估对PSA-TRICOM前列腺癌的免疫反应 疫苗此外，我们还评估了对匙孔血蓝蛋白（KLH）的反应， 用于预防膀胱癌术后复发免疫抑制剂。

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.