Polysialic acid is associated with immune activation in human peripheral blood nuclear cells

Immune dysregulation is a persistent state in which cells of the immune system become activated at low levels for long periods of time. If left unchecked, this chronic inflammation can lead to the development of chronic inflammatory diseases, including cancer, heart disease, autoimmune disease, and neurodegenerative disease. Glycans, especially sialic acids, are critical regulators of immune cell functions in health and disease. One specialized form of sialic acid that remains relatively understudied is polysialic acid (polySia), a long homopolymer comprised of α2,8-linked sialic acids in humans. The role(s) of polySia in altering immune cell functions in various immune cell subtypes in both health and disease remains limited but is a rapidly developing area of research. In this study, we used cigarette smoking as a model for chronic inflammation and performed the first in-depth characterization of polySia in human peripheral blood mononuclear cells (PBMCs) from smokers and age/sex-matched non-smokers. PolySia was expressed across all major myeloid and lymphoid immune cell types, but striking differences were observed among different immune subsets. Surface expression of polySia correlated with prior antigen exposure, especially in T cells, and could be induced within 24-72 hours following activation of naïve T cells. Dysregulation of polySia was observed in monocytes, antibody secreting B cells, and CD8+ T cells from smokers. While no sex differences were observed in healthy human PBMCs, we discovered that smoking had a differential effect on polySia expression in males and females, particularly for non-classical monocytes and CD8+ T cells.