On the analysis of antibody repertoires

Sammanfattning: The antibody repertoire is the ensemble of antibodies found in an individual at a given time. It displays high heterogeneity between individuals while being both largely temporally stable within an individual and rapidly responsive to immunological challenge. As distinct collections of antibodies within the repertoire contribute to the function and malfunction of the immune system, studying the many aspects of the antibody repertoire can give increased knowledge on antibody-mediated pathogen defense and autoimmune conditions.There are several emergent techniques for assessing different properties of the antibody repertoire as well as determining distinct antibodies of interest in health and disease. The studies presented in this thesis use planar and bead-based arrays to investigate parts of the antibody repertoire consisting of antibodies against SARS-CoV-2 proteins in serological studies, as well as autoantibodies against the large collection of antigens in the Human Protein Atlas. Paper I explores the autoantibody repertoires of patients with psychosis using planar arrays of 42 000 antigens followed by targeted bead arrays and identifies associations to specific symptoms. Paper II defines the baseline serological characteristics of a longitudinal cohort using a then recently developed multiplex serological assay and gives an early description of COVID-19 symptomatology. Paper III investigates the four-month persistence and antigen diversity of antibodies against SARS-CoV-2 following infection. This work is continued in Paper IV which examines the persistence of the humoral and cellular response to infection and their protective effect against reinfection. Paper V connects these parts by exploring the autoantibody repertoire of this longitudinal cohort and identifying new-onset autoantibodies emerging at infection using arrays of human and viral antigens. It associates three new-onset autoantibodies to post-COVID-19 symptoms and demonstrates sequence similarity between human and viral epitopes, which may indicate molecular mimicry.Antibody repertoires are heterogeneous and multifaceted, requiring several methods for full comprehension. The present investigation encompasses the analysis of one facet using antigen arrays and contributes to knowledge on disease-associated autoantibody repertoires as well as the prevalence and persistence of the serological and autoantibody response emerging after viral infection. This work represents a small step towards the goal of understanding the full repertoire complexity. Emergent large-scale techniques combined with the herein described analysis are together poised to identify clinically relevant antigens and advance knowledge on the diversity and heterogeneity of the antibody repertoire.