Uncovering the functional and genomic defects driving Predominantly Antibody Deficiency

Inborn Errors of Immunity (IEIs) are caused by rare genetic variants, yet many patients especially those with Predominantly Antibody Deficiency (PAD), the most common IEI in Australia remain genetically undiagnosed. Despite advances in genomics, 75% of PAD cases lack an identified genetic cause, leading to diagnostic delays of up to 9 years, missed treatment opportunities, and severe health consequences. We hypothesise that some undiagnosed PAD/IEI cases 1) are due to functional impairments in pathways important for immune development and function, and/or 2) are due to interactions between multiple rare or common variants in different genes. To investigate this, we will assess immune signalling pathways in B cells, T cells, and monocytes, and where possible link functional defects to underlying genetic variants using available patient samples, functional assays and whole exome sequencing data. Students will learn to isolate PBMCs from patient blood, perform functional immune assays, culture human cell lines, and analyse multicolour spectral flow cytometry data using FlowJo. This project aims to improve our understanding of PAD/IEI pathogenesis, leading to better diagnosis and treatment.