Understanding the pathogenesis of monogenic primary immunodeficiency (PID) with atopic presentation has important implications for therapeutic methods as well as possibly larger polygenic atopic-related characteristics. This review will address gene finding advancements resulting from monogenic abnormalities at the interface of PID and atopy, namely the hyper-IgE disorders. Recently, key molecular mechanisms underpinning the development of primary atopic disorders have been suggested. The researchers put this categorization to the test by evaluating new genes discovered in the previous two years and comparing findings from pathway analyses of genome-wide association studies (GWAS) of atopic characteristics. Growing availability to next-generation sequencing (NGS) has led to an increase in gene discovery, emphasising the value of this method in clinical practise as well as some of its drawbacks. This has significant implications for treatment methods such as protein stabilisation and JAK-STAT or TH2-cytokine signalling modulators. They also discuss the therapeutic implications of CARD11 deficiency, as well as the broader uses of NGS, such as polygenic risk score in atopy.
Disorders appearing at the border of PID and allergies are frequently difficult to diagnose, with significant implications if ignored. The use of NGS has already offered crucial insights into pathways that allow for focused treatment approaches, as well as potential wider translation to polygenic diseases.
