The Expression Profile of De-N-acetyl Polysialic Acid (NeuPSA) in Normal and Diseased Human Tissue

A cancer-unique glycan: de-N-acetyl polysialic acid (dPSA) linked to cell surface nucleolin depends on re-expression of the fetal polysialyltransferase ST8SIA2 gene

“…Protein polysialylation is highly restricted. To date, only ve proteins in humans are reported to be modi ed by polysialylation [21]: NCAM [5], E-selectin ligand-1 [7], the scavenger receptor CD36 [8], neuropilin-2 [4], and STX itself [6]. In this study, none of the previously known polysialylated proteins were co-immunoprecipitated from any of the cancer cell lines tested or human normal PBMCs with anti-dPSA antibodies suggesting that dPSA modi cation is exclusive to nucleolin.…”

“…Intracellular antigens reactive with both SEAM 2 and SEAM 3 were reduced but still detected in detergenttreated cells after knocking out ST8SIA2, ST8SIA4 or both genes in CHP-134 cells and in normal PBMCs that do not express ST8SIA2 suggesting that the internal staining described previously [21] may result from cross-reactivity with an antigen that does not depend on either STX or PST1. For example, an intracellular sialylated glycan produced by another sialyltransferase that is subsequently de-N-acetylated [26,41,42].…”

“…Previously, we reported the discovery of a de-N-acetylated form of PSA (dPSA) and of anti-dPSA antibodies that were reactive with dPSA antigens [19,20] on placental trophoblasts, the surface of cancer cells, and inside some normal cells within the perinuclear space [21,22]. Also, human microbial pathogens that produce PSA, including Neisseria meningitidis serogroup B [19] and Leishmania major [23], display cell surface dPSA under conditions corresponding to encountering a human host [23,24].…”

“…Since anti-dPSA mAbs have direct cytotoxic effects on multiple cancer cell lines [22], approaches that target ST8SIA2 and dPSA to prevent and treat cancers without adverse effect on normal cells may be possible. The presence of dPSA on human trophoblasts [21], microbial pathogens [23,24,47], and cancer cells [21,22] raises the possibility that the function of dPSA may be related to an unrecognized mechanism of immune shielding, since all of the above have in common a need to avoid being targeted by immunological mechanisms of protection.…”

Effect of Vaccine-Elicited Antibodies on Colonization of Neisseria meningitidis Serogroup B and C Strains in a Human Bronchial Epithelial Cell Culture Model

“…While herd protection was demonstrated in many epidemiological studies ( 3 , 8 – 10 ), the mechanisms by which PS-conjugate vaccine-elicited antibodies exert this effect remained unknown. The question of mechanism has become particularly important with the introduction of protein-based vaccines to protect against disease caused by MenB, whose capsular polysaccharide is similar to host polysialic acid, thus precluding the development of MenB PS-conjugate vaccines ( 26 , 27 ). To address the question of mechanism, we characterized the effect of MenC-conjugate-elicited IgG compared to that with IgG elicited by other vaccines known to not affect colonization or provide herd protection or, in the case of the newly licensed “MenB vaccines” ( 16 ), to have unknown effects on colonization.…”