Low amounts of bisecting glycans characterize cerebrospinal fluid-borne IgG

Knopf, Jasmin; Magorivska, Iryna; Maler, Juan Manuel; Spitzer, Philipp; Bilyy, Rostyslav; Biermann, Mona; Hychka, К.М.; Bondt, Albert; Wuhrer, Manfred; Toes, René E. M.; Schett, Georg; Herrmann, Martin; Muñoz, Luis

doi:10.1016/j.jneuroim.2018.04.010

Cited by 5 publications

(5 citation statements)

References 33 publications

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“…Elevated bisecting GlcNAc and reduced galactosylation are known to enhance IgG effector functions; however elevated core fucosylation has the opposite effect. Nonetheless, another recent study conversely observed that IgG from CSF of MS patients is characterized by significantly reduced bisecting GlcNAc [ 19 ], confounding the previous observations. Conversely, all glycosylation changes observed herein are jointly suggesting the enhanced proinflammatory potential of the circulating IgG.…”

Section: Discussionmentioning

confidence: 92%

“…Research studies focused on alterations of IgG or total plasma protein N-glycome in MS are scarce. One study examined IgG glycosylation pattern in cerebrospinal fluid (CSF) [ 19 ], while another tackled MS-related IgG1 glycosylation changes in serum and CSF [ 20 ]. In general, the presence of oligoclonal IgG in CSF is considered to be a hallmark of MS [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential

et al. 2020

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Multiple sclerosis (MS) is an inflammatory autoimmune disorder affecting the central nervous system (CNS), with unresolved aetiology. Previous studies have implicated N-glycosylation, a highly regulated enzymatic attachment of complex sugars to targeted proteins, in MS pathogenesis. We investigated individual variation in N-glycosylation of the total plasma proteome and of IgG in MS. Both plasma protein and IgG N-glycans were chromatographically profiled and quantified in 83 MS cases and 88 age- and sex-matched controls. Comparing levels of glycosylation features between MS cases and controls revealed that core fucosylation (p = 6.96 × 10−3) and abundance of high-mannose structures (p = 1.48 × 10−2) were the most prominently altered IgG glycosylation traits. Significant changes in plasma protein N-glycome composition were observed for antennary fucosylated, tri- and tetrasialylated, tri- and tetragalactosylated, high-branched N-glycans (p-value range 1.66 × 10−2–4.28 × 10−2). Classification performance of N-glycans was examined by ROC curve analysis, resulting in an AUC of 0.852 for the total plasma N-glycome and 0.798 for IgG N-glycome prediction models. Our results indicate that multiple aspects of protein glycosylation are altered in MS, showing increased proinflammatory potential. N-glycan alterations showed substantial value in classification of the disease status, nonetheless, additional studies are warranted to explore their exact role in MS development and utility as biomarkers.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential

et al. 2020

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“…Lectin-ELISA testing of the α1,6-fucosyl core residue (core fucose) of N-glycan of IgG immunoglobulins was performed using AAL lectin. The principle of the validated test [3,7,14] is demonstrated in the insert of Fig. 2, a. Localization of the detected glycan in the IgG molecule can be ascertained from Fig.…”

Section: Resultsmentioning

confidence: 99%

“…N-glycan residues attached to asn297 of the immunoglobulin IgG molecule are responsible for changing itsstructuralconformationandareusedasmarkersofmanyinflammatorydiseases. Freezingstabi introduction Glycosylation of IgG (both native and artificially produced pharmaceutical monoclonal formulations [most are IgG]) has become an intensely growing "hot topic" in biomedical and pharmaceutical sciences [1], with studies of IgG glycans used to discriminate clinical conditions [2] and identify their roles in specific neurological conditions [3]. N-glycan residues attached to Asn297 of the IgG molecule are responsible for changing its structural conformation and subsequently the affinity towards pro-and anti-inflammatory receptors on effector cells [4].…”

mentioning

confidence: 99%

Freezing influences, the exposure of IgG glycans in sera from multiple sclerosis patients

Боженко¹,

Boichuk²,

Bila³

et al. 2020

Ukr.Biochem.J.

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“…To characterize the glycosylation of IgG Fc, we additionally employed Liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). Total IgG was purified from serum using Protein G Sepharose (GE Healthcare, Chicago, IL, USA) and the IgG eluates were digested with sequencing grade modified trypsin (Promega) overnight at 37 • C. The IgG peptides were then analyzed for specific Fc-glycans as described in Knopf et al [71]. Briefly, detected mass spectra were analyzed for the typical retention times of IgG1, IgG2 and IgG3 glycopeptides using the Compass DataAnalysis software V5.0 (Bruker, Billerica, MA, USA) and specific glycans were extracted from the data using LaCyTools [72].…”

Section: Lc-esi-ms Analyses Of Igg Fc Glycosylationmentioning

confidence: 99%

Neutrophil Depletion Changes the N-Glycosylation Pattern of IgG in Experimental Murine Sepsis

Yaykasli,

van Schie,

Toes

et al. 2024

IJMS

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Sepsis is a life-threatening condition with a rising disease burden worldwide. It is a multifactorial disease and is defined as a dysregulated host response to infection. Neutrophils have been shown to be involved in the pathogenesis of sepsis by exacerbating inflammation. However, the exact effector mechanism of action still remains a mystery. Changes in the glycosylation pattern of the immunoglobulin G (IgG) Fc region are described for several diseases including meningococcal sepsis. In this study, we investigated the possible contribution of neutrophils and neutrophil implication, potentially related to degranulation or neutrophil extracellular trap (NET) formation in changing the IgG Fc N-glycosylation pattern in a murine sepsis model. We have measured the serum level of cytokines/chemokines and immunoglobulins, the serum activity of neutrophil elastase (NE), and analyzed the IgG Fc glycosylation pattern by Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (LC-ESI-MS) and Lectin enzyme-linked immunosorbent assay (ELISA). We observed an increased activity of NE- and neutrophil-associated cytokines such as keratinocyte chemoattractant (KC) with the development of sepsis. Regarding the IgG Fc N-glycosylation, we observed an increase in fucosylation and α1,3-galactosylation and a decrease for sialyation. Interestingly, these changes were not uniform for all IgG subclasses. After depletion of neutrophils, we saw a change in the exposure of fucose and α2,6-linked sialic acid during the time course of our experimental sepsis model. In conclusion, neutrophils can influence changes in the IgG glycosylation pattern in experimental sepsis.

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Low amounts of bisecting glycans characterize cerebrospinal fluid-borne IgG

Cited by 5 publications

References 33 publications

Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential

Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential

Freezing influences, the exposure of IgG glycans in sera from multiple sclerosis patients

Neutrophil Depletion Changes the N-Glycosylation Pattern of IgG in Experimental Murine Sepsis

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