Polyclonal Immunoglobulin G N-Glycosylation in the Pathogenesis of Plasma Cell Disorders
| Autor: | Annemarie Larkin, Giao Le, Peter O'Gorman, Colin Clarke, Silvia Millán Martín, Jonathan Bones, Stefan Mittermayr |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Glycan Glycosylation Plasma cell Immunoglobulin light chain Biochemistry Immunoglobulin G 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine N-linked glycosylation Polysaccharides hemic and lymphatic diseases medicine Humans Multiple myeloma Aged biology Chemistry General Chemistry Middle Aged medicine.disease carbohydrates (lipids) 030104 developmental biology medicine.anatomical_structure Polyclonal antibodies 030220 oncology & carcinogenesis biology.protein Female Neoplasm Recurrence Local Multiple Myeloma |
| Zdroj: | Journal of Proteome Research. 16:748-762 |
| ISSN: | 1535-3907 1535-3893 |
| Popis: | The pathological progression from benign monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM) and finally to active myeloma (MM) is poorly understood. Abnormal immunoglobulin G (IgG) glycosylation in myeloma has been reported. Using a glycomic platform composed of hydrophilic interaction UPLC, exoglycosidase digestions, weak anion-exchange chromatography, and mass spectrometry, polyclonal IgG N-glycosylation profiles from 35 patients [MGUS (n = 8), SMM (n = 5), MM (n = 8), complete-response (CR) post-treatment (n = 5), relapse (n = 4), healthy age-matched control (n = 5)] were characterized to map glycan structures in distinct disease phases of multiple myeloma. N-Glycan profiles from MGUS resembled normal control. The abundance of neutral glycans containing terminal galactose was highest in SMM, while agalactosylated glycans and fucosylated glycans were lowest in MM. Three afucosyl-biantennary-digalactosylated-sialylated species (A2G2S1, A2BG2S1, and A2BG2S2) decreased 2.38-, 2.4-, and 4.25-fold, respectively, from benign to active myeloma. Increased light chain sialylation was observed in a longitudinal case of transformation from MGUS to MM. Bisecting N-acetylglucosamine was lowest in the CR group, while highest in relapsed disease. Gene expression levels of FUT 8, ST6GAL1, B4GALT1, RECK, and BACH2 identified from publicly available GEP data supported the glycomic changes seen in MM compared to control. The observed differential glycosylation underlined the heterogeneity of the myeloma spectrum. This study demonstrates the feasibility of mapping glycan modifications on the IgG molecule and provides proof of principle that differential IgG glycosylation patterns can be successfully identified in plasma cell disorders. |
| Databáze: | OpenAIRE |
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