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

Primary immunodeficiencies are group disorders that are characterised by an impaired function of the immune system. Predominantly primary antibody deficiencies among adults (PAD) are the most widespread primary imunodeficiencies. PAD is characterised by impaired B-cell differentiation, defective immunoglobulin production and decreased response to immunisation. Clinical manifestations and age of onset are very variable. The mechanisms causing these disorders are mostly unknown; genetic causes could only be identified in 15-30% cases. Additionally, a 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). The project group will utilise clinical data of population-based PAD cohort and will analyse the role of inherited and acquired/mosaic variants and of clonal hematopoiesis in PAD development, as well as perform integrative analysis of whole genome sequencing and transcriptome data and perform PAD patient immunophenotyping. The project will yield important information regarding etiology and clinical variability of PAD, providing better diagnostics and personalised treatment options.