Increased sialylation of oligosaccharides on IgG paraproteins--a potential new tumour marker in multiple myeloma.
OBJECTIVE
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.
Fleming
S C
SC
Department of Clinical Biochemistry, University of Newcastle upon Tyne, UK.
Smith
S
S
Knowles
D
D
Skillen
A
A
Self
C H
CH
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000175:diagnosis; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000473:pathology; D019158:N-Acetylneuraminic Acid / Q000097:blood; D009363:Neoplasm Proteins / Q000097:blood; D009367:Neoplasm Staging; D009844:Oligosaccharides / Q000097:blood* / Q000737:chemistry; D010266:Paraproteins / Q000032:analysis* / Q000737:chemistry
D014408:Biomarkers, Tumor; D007074:Immunoglobulin G; D009363:Neoplasm Proteins; D009844:Oligosaccharides; D010266:Paraproteins; D019158:N-Acetylneuraminic Acid