IgG N-glycome changes during the course of severe COVID-19: An observational study

Petrović, Tea; Vijay, Amrita; Vučković, Frano; Trbojević‐Akmačić, Irena; Ollivere, B.; Marjanović, Damir; Bego, Tamer; Prnjavorac, Besim; Đerek, Lovorka; Markotić, Alemka; Lukšić, Ivica; Jurin, Ivana; Valdes, Ana M.; Hadžibegović, Irzal; Lauc, Gordan

doi:10.1016/j.ebiom.2022.104101

Cited by 19 publications

(9 citation statements)

References 35 publications

(59 reference statements)

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“…In comparison, the sialyation of severe patient IgG N-glycans remained lowered or unchanged on day 4 compared to healthy controls (Fig. 2A), aligning with previous studies of IgG N-glycosylation in hospitalized COVID-19 patients [24,27,28]. Lastly, the decrease in mannose remained signi cant in severe trajectory patients compared to nonsevere patients on day 4 of hospitalization.…”

Section: Igg and Igm N-glycans Responses Differ During Covid-19supporting

confidence: 89%

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: Igg and Igm N-glycans Responses Differ During Covid-19supporting

confidence: 89%

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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“…37 The proinflammatory IgG N-glycosylation pattern also includes reduced fucosylation. 38,39 Highly afucosylated IgG (lack of fucose) immune complexes can trigger the increased production of proinflammatory cytokines compared with immune complexes with low afucosylation. 38,40 In this study, lower IgG galactosylation was also observed in patients with CTEPH, and positive associations of proinflammatory IgG N-glycan traits (agalactosylation, G0/G2, Gal-ratio, and H3N4F1, representing lower galactosylation) and negative associations of anti-inflammatory IgG glycan traits (galactosylation and fucosylation) with circulating inflammatory cytokines were found in patients with CTEPH.…”

Section: Discussionmentioning

confidence: 99%

Human Plasma IgG N -Glycome Profiles Reveal a Proinflammatory Phenotype in Chronic Thromboembolic Pulmonary Hypertension

et al. 2023

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BACKGROUND: The pathological mechanism of chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood, and inflammation has been reported to be one of its etiological factors. IgG regulates systemic inflammatory homeostasis, primarily through its N -glycans. Little is known about IgG N -glycosylation in CTEPH. We aimed to map the IgG N -glycome of chronic thromboembolic pulmonary hypertension to provide new insights into its pathogenesis and discover novel markers and therapies. METHODS: We characterized the plasma IgG N -glycome of patients with chronic thromboembolic pulmonary hypertension in a discovery cohort and validated our results in an independent validation cohort using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Thereafter, we correlated IgG N -glycans with clinical parameters and circulating inflammatory cytokines in patients with CTEPH. Furthermore, we determined IgG N -glycan quantitative trait loci in chronic thromboembolic pulmonary hypertension to reveal partial mechanisms underlying glycan changes. RESULTS: Decreased IgG galactosylation representing a proinflammatory phenotype was found in CTEPH. The distribution of IgG galactosylation showed a strong association with NT-proBNP (N-terminal pro-B-type natriuretic peptide) in CTEPH. In line with the glycomic findings, IgG pro-/anti-inflammatory N -glycans correlated well with a series of inflammatory markers and gene loci that have been reported to be involved in the regulation of these glycans or inflammatory immune responses. CONCLUSIONS: This is the first study to reveal the full signature of the IgG N -glycome of a proinflammatory phenotype and the genes involved in its regulation in CTEPH. Plasma IgG galactosylation may be useful for evaluating the inflammatory state in patients with CTEPH; however, this requires further validation. This study improves our understanding of the mechanisms underlying chronic thromboembolic pulmonary hypertension inflammation from the perspective of glycomics.

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“… 73 , 74 While similar yields were observed to result from affinity purification against HLA-A2 with each of two different peptides in a pilot experiment, peptide occupancy and identity may also impact results of the assays used. Antibody glycosylation can be somewhat dynamic 102 , 103 but was tested at a single time point. Lastly, while a direct association has been made between afucosylation of DSAs and the occurrence of AMR, HLA-A2-specific antibodies were first detected in most of the patients post-rejection, suggesting that afucosylation of DSAs may have occurred as a result of AMR.…”

Section: Discussionmentioning

confidence: 99%

Afucosylation of HLA-specific IgG1 as a potential predictor of antibody pathogenicity in kidney transplantation

Bharadwaj

Shrestha

Pongrácz

et al. 2022

Cell Reports Medicine

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IgG N-glycome changes during the course of severe COVID-19: An observational study

Cited by 19 publications

References 35 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

Human Plasma IgG N -Glycome Profiles Reveal a Proinflammatory Phenotype in Chronic Thromboembolic Pulmonary Hypertension

Afucosylation of HLA-specific IgG1 as a potential predictor of antibody pathogenicity in kidney transplantation

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