Applications of multiplexed immunoassays for precision medicine

QC 2026-01-15

Abstract

Proteins are molecules that play central roles in almost all biological processes. Their abundance in cells, tissues, and body fluids is dynamic, reflecting both physiological states and disease-related changes. When studying proteins, a major challenge is distinguishing normal biological variation from alterations that indicate early or ongoing disease. Using proteomics, a term that describes measuring hundreds of proteins at the same time, will deepen our understanding of how protein signatures relate to health and disease. This will assist to establish molecular measurements of so-called biomarkers that support precision medicine through earlier detection, better disease stratification, and more individualized treatment strategies. 

In the studies included in this thesis, we applied affinity proteomics techniques to investigate how levels of antibodies and proteins in blood samples related to health and disease and to expand our understanding of protein-protein interactions of drug targets. 

Although proteins can be measured in different sample types, blood offers a minimally invasive window into our body and to measure molecules coming from many organs and biological processes. Home-sampled dried blood spots (DBS) has gained renewed interest due to the recent development of newer and more accurate sampling cards. In several studies included in this thesis, we demonstrate that DBS can be used in the general population sampling without relying on or involving clinical facilities and healthcare resources. In Paper I, we established an analytical procedure for measuring home-sampled DBS for antibodies against SARS-CoV-2. In Paper II, we expanded this effort to protein measurements and longitudinal sampling. In Paper III, we showed the importance of even more frequent DBS sampling for capturing the dynamic changes of inflammation-related proteins following infection. This demonstrated how these early changes in DBS protein levels can support the timing of clinical interventions. Together, these findings of our studies highlight the potential of DBS for remote and continuous health monitoring for precision health approaches.

Proteins are also among the most common targets of therapeutic drugs. Still, many proteins interact also with other proteins, and such complexes can critically influence how a drug binds to its target, its therapeutic efficacy, and the risk of side effects. In Paper IV, we established an affinity proteomics workflow for validating binding reagents, which we then applied in Paper V to investigate potential protein-protein interactions of membrane proteins. The gained insights and knowledge can contribute to improve our understanding of biologically relevant protein interactions aiding the development of more selective and effective drug candidates. 

Overall, the studies presented in this thesis contribute with valuable insights to the transition toward precision health by enabling scalable remote sampling and by deepening our understanding of protein interactions relevant to both normal physiology and disease.

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