Immunoglobulin G1 Fc glycosylation as an early hallmark of severe COVID-19

Pongrácz, Tamás; Nouta, Jan; Wang, Wenjun; Meijgaarden, Krista E. van; Linty, Federica; Vidarsson, Gestur; Joosten, Simone A.; Ottenhoff, Tom H. M.; Hokke, Cornelis H.; Vries, Jutte J.C. de; Arbous, Sesmu; Roukens, Anna H E; Wuhrer, Manfred

doi:10.1016/j.ebiom.2022.103957

Cited by 51 publications

(80 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, anti-S IgG1 galactosylation has been shown to drop rapidly in ICU-admitted COVID-19 patients, as previously described (Fig. 2B) ( 2, 30 ). A high level of IgG galactosylation boosted the classical complement pathway activation capacity through enhanced C1q-binding, which was in line with previous reports (Fig.…”

Section: Resultssupporting

confidence: 82%

“…Recent work from Farkash et al and Chakraborty et al did not pick up this transient response due to sampling of two and four weeks after the first dose, respectively ( 26, 41 ). This afucosylated response was similar, but less pronounced than observed in natural SARS-CoV-2 infections ( 2, 30 ). The transient afucosylated IgG1 glycosylation pattern after vaccination suggests that a co-stimulus may be missing to induce memory B cells and long-lived IgG + PCs producing stable anti-S IgG1 afucosylation levels.…”

Section: Discussionsupporting

confidence: 58%

“…Anti-S IgG Abs were affinity-captured from plasma or sera using recombinant, in-house produced trimerized spike protein-coated plates (Thermo Fisher Scientific, Roskilde, Denmark) followed by a 100 mM formic acid elution step, as described elsewhere ( 2, 49 ). Total IgG Abs were affinity-captured from plasma or sera using a Protein G AssayMAP Cartridge Rack on the Bravo (Agilent Technologies, Santa Clara, CA) or Protein G Sepharose 4 Fast Flow beads (GE Healthcare, Uppsala, Sweden) in a 96-well filter plate (Millipore Multiscreen, Amsterdam, Netherlands), respectively, as described elsewhere( 2, 30, 52 ).…”

Section: Methodsmentioning

confidence: 99%

“…Eluates from both anti-S and total IgG affinity-purification were dried by vacuum centrifugation and subjected to tryptic cleavage followed by LC-MS analysis as described previously ( 2, 30 ).…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not antigen-experienced vaccinees

Coillie

Pongrácz

Rahmöller

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

The onset of severe SARS-CoV-2 infection is characterized by the presence of afucosylated IgG1 responses against the viral spike (S) protein, which can trigger exacerbated inflammatory responses. Here, we studied IgG glycosylation after BNT162b2 SARS-CoV-2 mRNA vaccination to explore whether vaccine-induced S protein expression on host cells also generates afucosylated IgG1 responses. SARS-CoV-2 naive individuals initially showed a transient afucosylated anti-S IgG1 response after the first dose, albeit to a lower extent than severely ill COVID-19 patients. In contrast, previously infected, antigen-experienced individuals had low afucosylation levels, which slightly increased after immunization. Afucosylation levels after the first dose correlated with low fucosyltransferase 8 (FUT8) expression levels in a defined plasma cell subset. Remarkably, IgG afucosylation levels after primary vaccination correlated significantly with IgG levels after the second dose. Further studies are needed to assess efficacy, inflammatory potential, and protective capacity of afucosylated IgG responses.One sentence summaryA transient afucosylated IgG response to the BNT162b2 mRNA vaccine was observed in naive but not in antigen-experienced individuals, which predicted antibody titers upon the second dose.

show abstract

Section: Resultssupporting

confidence: 82%

Section: Discussionsupporting

confidence: 58%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not antigen-experienced vaccinees

Coillie

Pongrácz

Rahmöller

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Glycopeptides were separated and detected with an Ultimate 3000 high-performance liquid chromatography (HPLC) system (Thermo Fisher Scientific, Waltham, MA) coupled to a maXis quadrupole time-of-flight mass spectrometer (Bruker Daltonics, Billerica, MA), as described (72). Data processing was performed according to established procedures (73).…”

Section: Methodsmentioning

confidence: 99%

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

Bharadwaj

Shrestha

Pongrácz

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Antibody-mediated rejection (AMR) is the leading cause of graft failure. While donor-specific antibodies (DSA) are associated with a higher risk of AMR, not all patients with DSA develop rejection suggesting that the characteristics of alloantibodies that determine their pathogenicity remain undefined. Using human leukocyte antigen (HLA)-A2-specific antibodies as a model, we applied systems serology tools to investigate qualitative features of immunoglobulin G (IgG) alloantibodies including Fc-glycosylation patterns and FcγR binding properties. The levels of afucosylation of anti-A2 antibodies were elevated in all seropositive patients and were significantly higher in AMR patients, suggesting potential cytotoxicity via FcγRIII-mediated mechanisms. Afucosylation of both glycoengineered monoclonal and naturally glycovariant polyclonal serum IgG specific to HLA-A2 exhibited potentiated binding to, slower dissociation from, and enhanced signaling through FcγRIII, a receptor widely expressed on innate effector cells. Collectively, these results suggest that afucosylated DSA may be a biomarker of AMR and could contribute to its pathogenesis.

show abstract

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

View full text Add to dashboard Cite

Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

show abstract

Immunoglobulin G1 Fc glycosylation as an early hallmark of severe COVID-19

Cited by 51 publications

References 43 publications

The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not antigen-experienced vaccinees

The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not antigen-experienced vaccinees

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

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Contact Info

Product

Resources

About