Increased sialylation of oligosaccharides on IgG paraproteins--a potential new tumour marker in multiple myeloma

• Published in: Journal of clinical pathology Vol. 51; no. 11; pp. 825 - 830
• Main Authors: Fleming, S C, Smith, S, Knowles, D, Skillen, A, Self, C H
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and Association of Clinical Pathologists 01.11.1998; BMJ
• Subjects: Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - blood; Chromatography, High Pressure Liquid; Cross-Sectional Studies; Diagnosis, Differential; Female; Hematologic and hematopoietic diseases; Humans; Immunoglobulin G - blood; Immunoglobulin G - chemistry; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Monoclonal Gammopathy of Undetermined Significance - diagnosis; Multiple Myeloma - diagnosis; Multiple Myeloma - pathology; N-Acetylneuraminic Acid - blood; Neoplasm Proteins - blood; Neoplasm Staging; Oligosaccharides - blood; Oligosaccharides - chemistry; Paraproteins - analysis; Paraproteins - chemistry; Human; Immunopathology; Oligosaccharide; IgG; Biological marker; Malignant hemopathy; Hemopathy; Tumoral marker; Myeloma; Chromatography; Differential diagnostic; Benign monoclonal immunoglobulinemia; Sialoglycoproteins; Immunoglobulinopathy; Lymphoproliferative syndrome
• ISSN: 0021-9746; 1472-4146
• DOI: 10.1136/jcp.51.11.825

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.