Altered Innate and Adaptive Immune Landscape in Pediatric Patients with Glycogen Storage Disease 1b

Patients with Glycogen Storage Disease 1b (GSD1b), resulting from SLC37A4 mutations, suffer from recurrent episodes of hypoglycemia, hepatosplenomegaly and recurrent infections attributed to chronic neutropenia. However, little is known about immune defects associated with the disease beyond abnormal neutrophil development. Utilizing a systems immunology approach with Cytometry by Time of Flight (CyTOF) analysis of blood samples from pediatric GSD1b patients aged 0.7-13.8 yrs and controls, we were able to characterize the peripheral immune landscape of GSD1b and investigate crucial changes in both adaptive and innate cell populations apart from the widely reported neutropenia: We show a decrease in macrophages, monocytes and natural killer cells as well as a shift from effector to central memory in T cells. Additionally, we observed both population-specific and global changes in expression of surface markers central to immune function such as CXCR3 and CD38, among others. These findings shine light on the complex dysregulation of the immune system accompanying GSD1b and uncover additional explanations for the observed clinical symptoms. Thereby our work contributes to our understanding of the disease and paves the way for future discoveries offering more specific and refined treatment methods.