Unraveling the dark matter of infectious diseases, environmental and genetic factors: tipping the balance towards Immune-related noncommunicable diseases

In this project, we aim to characterize antibody, T- and B-cell receptor structure and variations using PhIP-Seq, TCR-Seq and BCR-Seq in individuals who reported to be healthy at baseline inclusion in Lifelines and who developed (at all follow-up assessments, so the second, third, and fourth rounds) immune-related noncommunicable diseases (IR-NCDs) such as post-COVID- 19 condition (PCC), multiple sclerosis (MS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), celiac disease, or inflammatory bowel disease (IBD) later in life. Application of PhIP-Seq and TCR/BCR-Seq technologies could provide us with a valuable and non-redundant resource of information that could be utilized to search for novel systemic biomarkers or specific microbiota-immune signatures that may be predictive of the early onset and development of these disease. Through comparison with a group of healthy individuals from which the same data will be generated, we aim to pinpoint specific B- and T-cell clonotypes and antibody repertories in the context of IR-NCDs, which could enable us to unravel novel disease-associated immune responses. As the interactions between infectious diseases, gut microbiota and host immunity are deemed to play a role in development of these diseases, the application of these high-throughput methods would provide us with a unique layer of immunological information that could help to better understand disease pathophysiology.