An Immunoproteomic Survey of the Antibody Landscape: Insights and Opportunities Revealed by Serological Repertoire Profiling

Immunoproteomics has emerged as a versatile tool for analyzing the antibody repertoire in various disease contexts. Until recently, characterization of antibody molecules in biological fluids was limited to bulk serology, which identifies clinically relevant features of polyclonal antibody responses. The past decade, however, has seen the rise of mass-spectrometry-enabled proteomics methods that have allowed profiling of the antibody response at the molecular level, with the disease-specific serological repertoire elucidated in unprecedented detail. In this review, we present an up-to-date survey of insights into the disease-specific immunological repertoire by examining how quantitative proteomics-based approaches have shed light on the humoral immune response to infection and vaccination in pathogenic illnesses, the molecular basis of autoimmune disease, and the tumor-specific repertoire in cancer. We address limitations of this technology with a focus on emerging potential solutions and discuss the promise of high-resolution immunoproteomics in therapeutic discovery and novel vaccine design.