Rare cell-based liquid biopsy for improved measurement of low-grade chronic inflammation

Abstract

Objectives and design: Low-grade inflammation is a hallmark of chronic diseases. More sensitive tools for chronic low-grade inflammation detection are needed and herein presented as a prove of concept. The proposed improvement involves investigating inflammation-induced stress imposed on hematopoietic cells and their production, focusing on highly sensitive compensatory mechanisms that address consequential imbalances in red blood cell and platelet concentrations. Such mechanisms involve the generation or release of blood circulating rare immature cell types. Methods: A cell-based liquid biopsy platform, using negative selection, was used to detect these circulating rare cells in comprehension, allowing simultaneous analysis of an immature cell panel from one sample. The concentration ranges under physiological conditions for each marker was evaluated on a self-reported healthy control cohort and prospectively tested on three individuals undergoing various interventions; one afflicted with early-stage breast cancer, another with atherosclerosis in follow up and a third healthy individual with cardiovascular disease risk. Results: The approach effectively identified rare cellular abnormalities in asymptomatic individuals who exhibited no abnormalities in their complete blood counts. This condition was designated as silent inflammation (SI). Conclusions: The detection of SI proved valuable in aiding inflammation differential diagnosis and for monitoring the response to interventions in all three subjects.