Increased Sialylation of Oligosaccharides on IgG Paraproteins--a Potential New Tumour Marker in Multiple Myeloma
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Aims: To investigate whether changes in carbohydrate structure of IgG are related to malignancy and stage of disease in myeloma and monoclonal gammopathy of uncertain significance (MGUS).
Methods: 61 patients were studied at diagnosis: 14 with MGUS, nine with stage I multiple myeloma, 11 with stage II, 21 with stage III, and five with solitary plasmacytoma. IgG was extracted from serum by protein G affinity chromatography. Oligosaccharides were cleaved from the protein backbone enzymatically by N-glycosidase F. Oligosaccharide analysis was performed by high pressure anion exchange chromatography with pulsed electrochemical detection (HPAE-PED).
Results: Up to 15 oligosaccharide peaks were identified in three major fractions: neutral, monosialylated, and disialylated. Patients with myeloma showed an increase in the proportion of sialylated oligosaccharides in comparison with patients with MGUS. The ratio of neutral to sialylated oligosaccharides (N:S) was reduced at all stages of myeloma compared with MGUS: MGUS, 11.35; myeloma stage I, 7.6 (p = 0.047); stage II, 5.20 (p = 0.035); stage III, 3.60 (p = 0.0002); plasmacytoma, 7.5 (p = 0.046). The N:S ratio was independent of paraprotein concentration (r = 0.05).
Conclusions: The ratio of neutral to sialylated oligosaccharides may act as a new marker of malignancy in IgG paraproteinaemia and warrants further investigation.
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Immunoglobulin G Glycosylation in Diseases.
Pezer M Exp Suppl. 2021; 112:395-431.
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Proteomics-inspired precision medicine for treating and understanding multiple myeloma.
Ho M, Bianchi G, Anderson K Expert Rev Precis Med Drug Dev. 2021; 5(2):67-85.
PMID: 34414281 PMC: 8372187. DOI: 10.1080/23808993.2020.1732205.
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Markina Y, Gerasimova E, Markin A, Glanz V, Wu W, Sobenin I Int J Mol Sci. 2020; 21(15).
PMID: 32751832 PMC: 7432344. DOI: 10.3390/ijms21155472.