Searching for biomarkers: humoral response profiling with luciferase immunoprecipitation systems

Abstract

B-cell-mediated humoral responses are triggered in many human diseases, including autoimmune diseases, cancer, and neurologic and infectious diseases. However, the full exploitation of the information contained within a patient’s antibody repertoire for diagnosis, monitoring and even disease prediction has been limited due to the poor diagnostic performance of many immunoassay formats. We have developed luciferase immunoprecipitation systems (LIPS) that harnesses light-emitting proteins to generate high-definition antibody profiles that are optimal for both diagnostics and biomarker discovery. Here, we describe the results and implications from a range of LIPS-antibody profiling studies performed in our laboratory. These include highly sensitive diagnostics for domestic and global pathogens, insights into infection-related diseases, discovery of new biomarkers for human diseases, subcategorization of symptoms and identification of pathogenic autoantibodies against self-proteins. These investigations highlight the types of humoral response profiles associated with different diseases, provide new information related to disease pathogenesis and offer a framework for incorporating LIPS antibody profiling into global health initiatives and disease monitoring.

Keywords::

• antibody profiling
• autoantibodies
• autoimmune
• biomarker
• chronic disease
• infectious disease
• luciferase immunoprecipitation systems

Acknowledgements

The authors thank the many patients who volunteered for these studies. We are also indebted to our many intramural and extramural collaborators.

Financial & competing interest disclosure

The laboratory that the authors work in is supported by the intramural research program of the National Institute of Dental and Craniofacial Research, NIH. Two of the authors (Peter D Burbelo and Michael J Iadarola) have patent applications submitted using luciferase immunoprecipitation system. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.