SLC35A3 has been characterized as UDP-GlcNAc transporter localized to the Golgi apparatus. Its activity is crucial in multiple glycosylation pathways, such as N- and O-linked glycosylation. Pathogenic variants in SLC35A3 gene lead to congenital disorder of glycosylation characterized by impaired Golgi glycosylation. We report a SLC35A3-CDG patient with a lethal skeletal dysplasia, bearing a novel variant, i.e., c.797 A > T p. Asp266Val, highlighting the importance of Asp 266 for conserved SLC35A3 function. The comprehensive biochemical and glycomic characterization of associated glycosylation abnormalities reveals that this variant disrupts mucin-type O-glycan branching and causes a tissue-specific remodeling of N-glycosylation. The contrast between plasma and fibroblast glycomes suggests that MGAT1-5 enzymes are disparately affected by the reduced UDP-GlcNAc availability. The observation of shortened chondroitin sulfate chains on bikunin, a polymer devoid of GlcNAc, may point to a broader involvement for SLC35A3 in Golgi nucleotide-sugar transport and homeostasis. Collectively, these findings suggest that defects in SLC35A3 may affect glycosylation through multiple mechanisms.
Glycans and glycoconjugates play a significant role in nearly all aspects of living organisms from birth through development to demise. For more than half a century, the aberrant glycosylation profiles on tumor cells have been discussed. However, in the past few decades scientists have validated how these modified glycans influence cancer development, progression and metastasis through bypassing immune surveillance and creating an immunosuppressive milieu in the tumor microenvironment. Although advancements in cancer immunotherapy have shown promise, it has only been able to enhance the overall survival of a small group of patients. Certain types of cancer remain undiagnosed and untreated until very late stages, due to the limited understanding of complex tumor immune resistance. The understanding and use of glycans and glycoconjugates help researchers to work towards broadening the benefits of cancer immunotherapy to a larger population. Many glycans and glycoconjugates have made their way to clinical trials but still the full potential of glycan-based materials has not been entirely harnessed. This comprehensive review outlines major developments in the field of glycoconjugate mediated cancer immunotherapy, with special emphasis on the most recent developments. While covering a wide range of glycan categories, attempts have been made to draw correlations between glycoconjugate structure and the primary immune response elicited by each of those glycan categories.
To investigate differences in cerebrospinal fluid (CSF) N-glycosylation profiles among children with purulent meningitis (PM), viral meningitis (VM), and disease controls (DC). This retrospective exploratory study included six children with PM, three with VM, and three children with leukemia in complete remission without central nervous system infection. CSF-derived extracellular vesicles(CSF-EVs)were characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. N-glycans were released using PNGase F, purified by porous graphitized carbon solid-phase extraction, and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Fifteen derived glycan traits were quantified. Group differences were assessed using Kruskal–Wallis tests with pairwise comparisons, and associations with clinical inflammatory markers were evaluated using Spearman correlation. CSF N-glycan profiles showed distinct patterns across the three groups. Hierarchical clustering based on glycan traits separated PM, VM, and DC samples. Compared with DC, both PM and VM showed altered sialylation, but their remodeling patterns differed. PM showed increased highly sialylated glycan traits, whereas VM showed increased disialylation and reduced galactosylation- and core fucosylation-associated traits. Bisecting GlcNAc-related traits were reduced in both infection groups. Total bisecting GlcNAc (B Total) was positively correlated with serum procalcitonin (PCT) levels (r = 0.681, P = 0.015). Pediatric CNS infections were associated with distinct CSF N-glycan remodeling patterns. These findings provide preliminary evidence of infection-associated glycosylation alterations and support further validation in larger cohorts.
