Predominantly primary antibody deficiencies among adults: solving etiology and causes of clinical variability

Primary immunodeficiencies (PID) are a group disorders that are characterized by an impaired function of the immune system. Predominantly primary antibody deficiencies among adults (PAD) are the most widespread primary imunodeficiencies. PAD is characterized by an impaired B-cell differentiation, defective immunoglobulin production and decreased response to immunization. Clinical manifestations and age-of-onset is very variable. Mechanisms causing these disorders are mostly unknown; in only 15-30% cases genetic causes could be identified. Additionally, our preliminary study shows that there is a significant diagnostic delay of PAD in Latvia. The aim of the project is to investigate the etiology and factors affecting the clinical variability of PAD among adults (genetic, transcriptomic and immunological). We will utilize clinical data of population-based PAD cohort and will analyze role of inherited and acquired/mosaic variants and of clonal hematopoiesis in PAD development, as well as we will perform integrative analysis of whole genome sequencing and transcriptome data and perform PAD patient immunophenotyping. The project will yield an important information regarding etiology and clinical variability of PAD, providing better diagnostics and personalized treatment options. We believe, that this project also will help to provide better recognition of primary immunodeficiencies in Latvia.