Personalized Immunomics: high-throughput and organ on chip technologies for biomarker discovery and therapeutic strategies in autoimmune diseases

In this PhD thesis, I used personalized medicine and immunomics to study Amyotrophic Lateral Sclerosis (ALS) and Rheumatoid Arthritis (RA). Early biomarker identification for diagnosis and treatment is essential for both diseases. My research at the Center for Autoimmune and Allergic Disease (CAAD) focuses on autoimmune diseases using personalized medicine. Personalized medicine tailors medical treatment to individual characteristics like genetic background and lifestyle to improve treatment efficacy and patient outcomes. Immunomics combines immunology with omics technologies to study the immune system comprehensively. ALS, a fatal disease with a short post-diagnosis life expectancy, requires early biomarker identification. Chapter 1 centers on finding ALS biomarkers at the ALS Centre, University Hospital “Maggiore della Carità” in Novara. We developed a method to identify extracellular vesicles (EVs) from liquid biopsies, showing platelet-derived EVs as biomarkers of Sars-CoV-2 infection. In ALS, astrocyte-specific EVs (GLAST+ EVs) were higher in patients, suggesting a diagnostic biomarker. Proteomic analysis of EVs revealed seven upregulated proteins, with proteoglycan-4 (PRG-4) potentially serving as a therapeutic target. Multiparametric flow cytometry identified immune cell changes in ALS patients, implicating basophils in ALS pathogenesis. Chapter 2 addresses RA, a chronic autoimmune disease. Early treatment is crucial, but current drugs are only effective for some patients. My thesis aimed to develop a personalized synovia-on-chip (SoC) model for precise drug testing, currently in patent application. This model promises to select the best drug for each patient, minimizing side effects and aiding new therapeutic target discovery. We also formulated a hydrogel for cultivating human fibroblasts in 3D. These studies underscore the role of personalized medicine and immunomics in improving outcomes for ALS and RA patients.