机构：[1]Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.[2]Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.[3]Department of Laboratory Medicine, Institute of Clinical Laboratory Medicine of People's Liberation Army (PLA), Xijing Hospital, Fourth Military Medical University, Xi'an 710061, China.[4]Department of Nephrology, Institutes for Systems Genetics, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院[5]Department of Nephrology, Yulin Hospital, The First Affiliated Hospital of Xi'an Jiaotong University, Yulin 719000, China.[6]Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Serum glycoprotein glycosylation changes can indicate disease onset and progression. However, the site-specific N-glycosylation of monoclonal immunoglobulins (M-proteins) in multiple myeloma (MM) and its clinical implications are unclear. In this study, we isolated pathogenic micromonoclonal IgA or IgG (approximately 2 μg) from IgA-MM patients (n = 22) and IgG-MM patients (n = 30), and normal polyclonal IgA and IgG from healthy controls (HCs) (n = 16). Using EThcD-sceHCD-MS/MS, the N-glycosylation dynamics of serum M-proteins in MM were determined. Compared with polyclonal IgA1 from HCs, monoclonal IgA1 from IgA-MM patients had higher fucosylation (58.1% vs 32.1%, p < 0.001), sialylation (68.0% vs 50.8%, p = 0.011), and mannosylation (1.5% vs 0.3%, p < 0.001). While, monoclonal IgG1 from IgG-MM patients had higher fucosylation (97.8% vs 95.3%, p < 0.001). In addition, specific N-glycan abundances correlated with MM clinical features: for IgA1, HexNAc5Hex5Fuc1NeuAc1 was associated with hypocomplementemia; for IgG1, HexNAc4Hex3Fuc1 was associated with the serum albumin level (r = -0.363, p = 0.049) and estimated glomerular filtration rate (r = -0.433, p = 0.017); and HexNAc4Hex5 was associated with therapeutic prognosis. In conclusion, monoclonal IgA1 and IgG1 in MM patients and their polyclonal isotypes in HCs have distinct N-glycosylation profiles, and specific N-glycans of M-proteins are associated with MM characteristics and therapeutic prognosis.
基金：
This work was
supported by the National Natural Science Foundation of
China grant (Nos. 82270747 and 81800639) and the
Institutional Foundation of the First Affiliated Hospital of
Xi’an Jiaotong University, China (2022YQPY05,
YXJLRH2022032). Y.Z. was supported by the National Key
R&D Program of China (2022YFF0608401). H.L. was
supported by the Natural Science Basic Research Program of
Shaanxi (2023-JC-QN-1001). W.Z. was supported by the
Science and Technology Program of Yulin (2024-SF-045).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2025]版：
大类|2 区生物学
小类|2 区生化研究方法
最新[2025]版：
大类|2 区生物学
小类|2 区生化研究方法
第一作者：
第一作者机构：[1]Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
通讯作者：
通讯机构：[1]Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.[6]Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
推荐引用方式(GB/T 7714)：
Li Huixian,Lu Wanhong,Jin Qian,et al.Deciphering N-Glycosylation Dynamics of Serum Monoclonal Immunoglobulins in Multiple Myeloma via EThcD-sceHCD-MS/MS[J].Journal Of Proteome Research.2025,24(5):2553-2563.doi:10.1021/acs.jproteome.5c00253.
APA：
Li Huixian,Lu Wanhong,Jin Qian,Sun Jiping,Gao Li...&Xie Xinfang.(2025).Deciphering N-Glycosylation Dynamics of Serum Monoclonal Immunoglobulins in Multiple Myeloma via EThcD-sceHCD-MS/MS.Journal Of Proteome Research,24,(5)
MLA：
Li Huixian,et al."Deciphering N-Glycosylation Dynamics of Serum Monoclonal Immunoglobulins in Multiple Myeloma via EThcD-sceHCD-MS/MS".Journal Of Proteome Research 24..5(2025):2553-2563
