N -linked glycosylation of the M-protein variable region: Glycoproteogenomics reveals a new layer of personalized complexity in multiple myeloma
N -linked glycosylation of the M-protein variable region: Glycoproteogenomics reveals a new layer of personalized complexity in multiple myeloma
ABSTRACT Multiple Myeloma (MM) is a plasma cell malignancy characterized by a monoclonal expansion of plasma cells that secrete a characteristic M-protein. This M-protein is crucial for diagnosis and monitoring of MM in the blood of patients. Recent evidence has emerged suggesting that N-glycosylation of the M-protein variable (Fab) region contributes to M-protein pathogenicity, and that it is a risk factor for disease progression of plasma cell disorders. Current methodologies lack the specificity to provide a site-specific glycoprofile of the Fab regions of M-proteins. Here, we introduce a novel glycoproteogenomics method that allows detailed M-protein glycoprofiling by integrating patient specific Fab region sequences (genomics) with glycoprofiling by glycoproteomics. Genomic analysis uncovered a more than two-fold increase in the Fab Light Chain N-glycosylation of M-proteins of patients with Multiple Myeloma compared to Fab Light Chain N-glycosylation of polyclonal antibodies from healthy individuals. Subsequent glycoproteogenomics analysis of 41 patients enrolled in the IFM 2009 clinical trial revealed that the majority of the Fab N-glycosylation sites were fully occupied with complex type glycans, distinguishable from Fc region glycans due to high levels of sialylation, fucosylation and bisecting structures. Together, glycoproteogenomics is a powerful tool to study de novo Fab N-glycosylation in plasma cell dyscrasias.
Langerhorst Pieter、Baerenfaenger Melissa、Wijnands Charissa、Post Merel A.、Dejoie Thomas、Lefeber Dirk J.、Gloerich Jolein、vanDuijn Martijn M.、Joosten Irma、van Gool Alain J.、Nadal Simon、Kulkarni Purva、Jacobs Joannes F.M.、Wessels Hans J.C.T.、Noori Somayya
Department of laboratory Medicine, Radboud University Medical CenterDepartment of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center||Division of BioAnalytical Chemistry, Vrije Universiteit AmsterdamDepartment of laboratory Medicine, Radboud University Medical CenterDepartment of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical CenterBiochemistry Laboratory, Centre Hospitalier Universitaire (CHU)Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical CenterDepartment of laboratory Medicine, Radboud University Medical CenterDepartment of Neurology, Erasmus University Medical CenterDepartment of laboratory Medicine, Radboud University Medical CenterDepartment of laboratory Medicine, Radboud University Medical CenterCY Cergy Paris Universit¨|, CNRS, BioCISDepartment of laboratory Medicine, Radboud University Medical Center||Medical BioSciences Department, Radboud University Medical Center||Department of Human Genetics, Radboud University Medical CenterDepartment of laboratory Medicine, Radboud University Medical CenterDepartment of laboratory Medicine, Radboud University Medical CenterDepartment of Neurology, Erasmus University Medical Center
医学研究方法基础医学肿瘤学
Langerhorst Pieter,Baerenfaenger Melissa,Wijnands Charissa,Post Merel A.,Dejoie Thomas,Lefeber Dirk J.,Gloerich Jolein,vanDuijn Martijn M.,Joosten Irma,van Gool Alain J.,Nadal Simon,Kulkarni Purva,Jacobs Joannes F.M.,Wessels Hans J.C.T.,Noori Somayya.N -linked glycosylation of the M-protein variable region: Glycoproteogenomics reveals a new layer of personalized complexity in multiple myeloma[EB/OL].(2025-03-28)[2025-07-22].https://www.biorxiv.org/content/10.1101/2023.04.05.535540.点此复制
评论