Zejian Zhang1, Marita Westhrin2, Albert Bondt3, Manfred Wuhrer4, Therese Standal2, Stephanie Holst5. 1. Center for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands; Department of Central Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, PR China. 2. Department of Clinical and Molecular Medicine and Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway. 3. Center for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands. 4. Center for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands. Electronic address: m.wuhrer@lumc.nl. 5. Center for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands. Electronic address: stephanie.holst@gmx.net.
Abstract
BACKGROUND: Multiple myeloma is characterized by clonal proliferation of malignant plasma cells in the bone marrow that produce monoclonal immunoglobulins. N-glycosylation changes of these monoclonal immunoglobulins have been reported in multiple myeloma, but previous studies only detected limited serum N-glycan features. METHODS: Here, a more detailed study of the human serum N-glycome of 91 multiple myeloma patients and 51 controls was performed. We additionally analyzed sequential samples from patients (n = 7) which were obtained at different time points during disease development as well as 16 paired blood serum and bone marrow plasma samples. N-glycans were enzymatically released and measured by mass spectrometry after linkage specific derivatization of sialic acids. RESULTS: A decrease in both α2,3- and α2,6-sialylation, galactosylation and an increase in fucosylation within complex-type N-glycans were found in multiple myeloma patients compared to controls, as well as a decrease in difucosylation of diantennary glycans. The observed glycosylation changes were present in all ISS stages, including the "low-risk" ISS I. In individual patients, difucosylation of diantennary glycans decreased with development of the disease. Protein N-glycosylation features from blood and bone marrow showed strong correlation. Moreover, associations of monoclonal immunoglobulin (M-protein) and albumin levels with glycan traits were discovered in multiple myeloma patients. CONCLUSIONS & GENERAL SIGNIFICANCE: In conclusion, serum protein N-glycosylation analysis could successfully distinguish multiple myeloma from healthy controls. Further studies are needed to assess the potential roles of glycan trait changes and the associations of glycans with clinical parameters in multiple myeloma early detection and prognosis.
BACKGROUND:Multiple myeloma is characterized by clonal proliferation of malignant plasma cells in the bone marrow that produce monoclonal immunoglobulins. N-glycosylation changes of these monoclonal immunoglobulins have been reported in multiple myeloma, but previous studies only detected limited serum N-glycan features. METHODS: Here, a more detailed study of the human serum N-glycome of 91 multiple myelomapatients and 51 controls was performed. We additionally analyzed sequential samples from patients (n = 7) which were obtained at different time points during disease development as well as 16 paired blood serum and bone marrow plasma samples. N-glycans were enzymatically released and measured by mass spectrometry after linkage specific derivatization of sialic acids. RESULTS: A decrease in both α2,3- and α2,6-sialylation, galactosylation and an increase in fucosylation within complex-type N-glycans were found in multiple myelomapatients compared to controls, as well as a decrease in difucosylation of diantennary glycans. The observed glycosylation changes were present in all ISS stages, including the "low-risk" ISS I. In individual patients, difucosylation of diantennary glycans decreased with development of the disease. Protein N-glycosylation features from blood and bone marrow showed strong correlation. Moreover, associations of monoclonal immunoglobulin (M-protein) and albumin levels with glycan traits were discovered in multiple myelomapatients. CONCLUSIONS & GENERAL SIGNIFICANCE: In conclusion, serum protein N-glycosylation analysis could successfully distinguish multiple myeloma from healthy controls. Further studies are needed to assess the potential roles of glycan trait changes and the associations of glycans with clinical parameters in multiple myeloma early detection and prognosis.
Authors: Calvin R K Blaschke; Colin T McDowell; Alyson P Black; Anand S Mehta; Peggi M Angel; Richard R Drake Journal: Clin Lab Med Date: 2021-04-24 Impact factor: 2.172