Immune dysregulation in glycogen storage disease 1b extends beyond neutropenia.

Glycogen Storage Disease type 1b (GSD1b) is a rare disease manifesting as hypoglycemia, recurrent infections and neutropenia, resulting from deleterious mutations in the SLC37A4 gene encoding the glucose-6-phosphate transporter. Classic treatment strategies in GSD1b focus on restoring neutrophil numbers and function; however, the immune defect is believed to be multifactorial and extensive immunophenotyping characterization is currently missing. Here we apply a systems immunology approach utilizing Cytometry by Time of Flight (CyTOF) to map the peripheral immune landscape of 6 GSD1b patients. When compared to control subjects, those with GSD1b had a significant reduction in immune sub-populations of classical monocytes, non-classical monocytes, and natural killer cells. Additionally, there was a preference towards a central versus an effector memory phenotype in multiple T cell populations. We also identified a global reduction of CD123, CD14, CCR4, CD24 and CD11b across several populations and a multi-cluster with upregulation of CXCR3, hinting at a potential role of impaired immune cell trafficking in the context of GSD1b. Taken together, our data suggest that that the immune impairment observed in GSD1b patients extends beyond neutropenia and affects innate and adaptive compartments, which may provide novel insights into the pathogenesis of this disorder.