Sialic acid level is significantly elevated in IgM enriched protein fraction in sera of cancer patients

Torii, Tsuyoshi; Kanemitsu, Kentaku; Hagiwara, Akeo

doi:10.1080/15321819.2016.1224973

Cited by 4 publications

(5 citation statements)

References 22 publications

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“…In contrast, we observe signi cant differences in IgM Nglycosylation stratifying COVID-19 disease severity with decreases only in the processed M5 and M6 Nglycans. Another group reported higher levels of sialic acid detected in IgM protein fraction isolated from cancer patient sera compared to non-cancer patients [45] while another study reported no signi cant glycomic response associated with either IgG or IgM N-glycan pro les following tumor ablation therapy [44]. Our ndings expand upon the previous reports of a general increase in sialic acid content on IgM.…”

Section: Igm N-glycosylationsupporting

confidence: 79%

“…While the N-glycosylation of IgM has been characterized previously in healthy pooled human serum, during cancer [35,[43][44][45], and in recombinant IgM [34,46], this is the rst characterization of the IgM Nglycosylation pro le isolated from humans infected with an acute viral disease. Here, we report signi cant differences in the IgM N-glycan content from cohorts of hospitalized COVID-19 separated by severity trajectory.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition

Haslund-Gourley,

Woloszcuk,

Hou

et al. 2023

Preprint

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The glycosylation of IgG plays a critical role during human SARS-CoV-2, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during acute viral infection in humans. In vitro evidence suggests that the glycosylation of IgM inhibits T cell proliferation and alters complement activation rates. The analysis of IgM N-glycosylation from healthy controls and hospitalized COVID-19 patients reveals that mannosylation and sialyation levels associate with COVID-19 severity. Specifically, we find increased di- and tri-sialylated glycans and altered mannose glycans in total serum IgM in severe COVID-19 patients when compared to moderate COVID-19 patients. This is in direct contrast with the decrease of sialic acid found on the serum IgG from the same cohorts. Moreover, the degree of mannosylation and sialylation correlated significantly with markers of disease severity: D-dimer, BUN, creatinine, potassium, and early anti-COVID-19 amounts of IgG, IgA, and IgM. Further, IL-16 and IL-18 cytokines showed similar trends with the amount of mannose and sialic acid present on IgM, implicating these cytokines' potential to impact glycosyltransferase expression during IgM production. When examining PBMC mRNA transcripts, we observe a decrease in the expression of Golgi mannosidases that correlates with the overall reduction in mannose processing we detect in the IgM N-glycosylation profile. Importantly, we found that IgM contains alpha-2,3 linked sialic acids in addition to the previously reported alpha-2,6 linkage. We also report that antigen-specific IgM antibody-dependent complement deposition is elevated in severe COVID-19 patients. Taken together, this work links the immunoglobulin M N-glycosylation with COVID-19 severity and highlights the need to understand the connection between IgM glycosylation and downstream immune function during human disease.

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Section: Igm N-glycosylationsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition

Haslund-Gourley,

Woloszcuk,

Hou

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In summary, sialic acid in a complex sample could easily be quantified by the HPLC and MS method, which could be applied in tumor research and diagnosis [26]. For example, sialic acid, quantified with fluorescence detection-HPLC in the IgM-enriched fraction, was significantly higher in cancer patients [112]. The sialylated proteins, as potentially cancer-associated proteins in serum, were quantified in prostate cancer using LC-MS/MS [113,114].…”

Section: Sialic Acids Quantificationmentioning

confidence: 99%

Biological Functions and Analytical Strategies of Sialic Acids in Tumor

Zhou

Yang

Guan

2020

Cells

120

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Sialic acids, a subset of nine carbon acidic sugars, often exist as the terminal sugars of glycans on either glycoproteins or glycolipids on the cell surface. Sialic acids play important roles in many physiological and pathological processes via carbohydrate-protein interactions, including cell–cell communication, bacterial and viral infections. In particular, hypersialylation in tumors, as well as their roles in tumor growth and metastasis, have been widely described. Recent studies have indicated that the aberrant sialylation is a vital way for tumor cells to escape immune surveillance and keep malignance. In this article, we outline the present state of knowledge on the metabolic pathway of human sialic acids, the function of hypersialylation in tumors, as well as the recent labeling and analytical techniques for sialic acids. It is expected to offer a brief introduction of sialic acid metabolism and provide advanced analytical strategies in sialic acid studies.

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“…Considering the increased sialic acid content on total and spike S1-specific IgM from patients with severe COVID-19, one publication reported higher levels of sialic acid detected in IgM isolated from cancer patients 49 . During severe COVID-19, increased sialylation is likely presented on IgM glycosylation sites: Asn-395, Asn-332, and Asn-171 which could participate in immunomodulatory signaling.…”

Section: Discussionmentioning

confidence: 99%

“…While the N-glycosylation of IgM has been characterized previously in healthy pooled human serum, during cancer 38 , 47 – 49 , and in recombinant IgM 37 , 50 , this is the first characterization of the IgM N-glycosylation profile isolated from humans with an acute viral infection. Here, we report significant differences in the total and antigen-specific IgM N-glycan content from cohorts of hospitalized COVID-19 patients separated by severity, contrast these findings with patient’s IgG N-glycans, and identify potential functional consequences of IgM N-glycosylation.…”

Section: Introductionmentioning

confidence: 94%

IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition

Haslund-Gourley,

Woloszczuk,

Hou

et al. 2024

Nat Commun

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The glycosylation of IgG plays a critical role during human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during human acute viral infection. The analysis of IgM N-glycosylation from healthy controls and hospitalized coronavirus disease 2019 (COVID-19) patients reveals increased high-mannose and sialylation that correlates with COVID-19 severity. These trends are confirmed within SARS-CoV-2-specific immunoglobulin N-glycan profiles. Moreover, the degree of total IgM mannosylation and sialylation correlate significantly with markers of disease severity. We link the changes of IgM N-glycosylation with the expression of Golgi glycosyltransferases. Lastly, we observe antigen-specific IgM antibody-dependent complement deposition is elevated in severe COVID-19 patients and modulated by exoglycosidase digestion. Taken together, this work links the IgM N-glycosylation with COVID-19 severity and highlights the need to understand IgM glycosylation and downstream immune function during human disease.

show abstract

Sialic acid level is significantly elevated in IgM enriched protein fraction in sera of cancer patients

Cited by 4 publications

References 22 publications

IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition

IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition

Biological Functions and Analytical Strategies of Sialic Acids in Tumor

IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition

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