Plasma glycomics predict cardiovascular disease in patients with ART‐controlled HIV infections

Oswald, Douglas M.; Sim, Edward S.; Baker, Claire; Farhan, Obada; Debanne, Sara M.; Morris, Nathan; Rodríguez, Benigno; Jones, Mark B.; Cobb, Brian A.

doi:10.1096/fj.201800923r

Cited by 11 publications

(14 citation statements)

References 36 publications

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“…Before analyzing the IgG itself, we also confirmed that the HcKO and BHcKO mice lacked ST6Gal1 activity in the plasma using a plate assay as we have previously described (27). We found that both the WT and BcKO strains showed strong ST6Gal1 activity in plasma samples when supplied with exogenous CMP-sialic acid, but neither the HcKO nor BHcKO mice showed detectable activity (Fig 5A).…”

Section: Resultssupporting

confidence: 74%

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Plasma ST6Gal1 is Dispensable for IgG Sialylation

Oswald

Lehoux

Zhou

et al. 2022

Preprint

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The glycosylation of IgG has attracted increased attention due to the impact of N-glycan modifications at N297 on IgG function, acting primarily through modulation of Fc domain conformation and Fcγ receptor binding affinities and signaling. However, the mechanisms regulating IgG glycosylation and especially α2,6-sialylation of its N-glycan remain poorly understood. We observed previously that IgG is normally sialylated in mice with B cells lacking the sialyltransferase ST6Gal1. This supported the hypothesis that IgG may be sialylated outside of B cells, perhaps through the action of hepatocyte-released plasma ST6Gal1. Here we demonstrate that this model is incorrect. Animals lacking hepatocyte expressed ST6Gal1 retain normal IgG α2,6-sialylation, despite the lack of detectable ST6Gal1 in plasma. Moreover, we confirmed that B cells were not a redundant source of IgG sialylation. Thus, while α2,6-sialylation is lacking in IgG from mice with germline ablation of ST6Gal1, IgG α2,6-sialylation is normal in mice lacking ST6Gal1 in either hepatocytes or B cells. These results indicate that IgG α2,6-sialylation arises after release from a B cell, but is not dependent on plasma-localized ST6Gal1 activity.

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Section: Resultssupporting

confidence: 74%

“…High throughput, multiplexed lectin ELISA was performed on whole plasma samples, as has been published (27,34). Briefly, plasma was diluted to 0.5 μg/ml in carbonate coating buffer (100 mM NaHCO 3 , 30 mM NaCO 3 , pH 9.5), pipetted into a 384 well black ELISA plate, and incubated overnight at 4 °C.…”

Section: Methodsmentioning

confidence: 99%

Plasma ST6Gal1 is Dispensable for IgG Sialylation

Oswald

Lehoux

Zhou

et al. 2022

Preprint

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“…Receiver Operating Characteristics (ROC) analysis, a well-established machine learning technique generating a model able to distinguish between different classes, already proved to be a valuable tool with enormous clinical potential in diagnosing several pathologies [ 51 , 52 , 53 , 54 ]. Nevertheless, this methodology is usually applied to samples obtained with invasive techniques, such as intravenous blood collection or biopsy.…”

Section: Resultsmentioning

confidence: 99%

Differential Glycosylation Levels in Saliva from Patients with Lung or Breast Cancer: A Preliminary Assessment for Early Diagnostic Purposes

et al. 2021

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Glycans play a fundamental role in several biological processes, such as cell–cell adhesion, signaling, and recognition. Similarly, abnormal glycosylation is involved in many pathological processes, among which include tumor growth and progression. Several highly glycosylated proteins found in blood are currently used in clinical practice as cancer biomarkers (e.g., CA125, PSA, and CA19-9). The development of novel non-invasive diagnostic procedures would greatly simplify the screening and discovery of pathologies at an early stage, thus also allowing for simpler treatment and a higher success rate. In this observational study carried out on 68 subjects diagnosed with either breast or lung cancer and 34 healthy volunteers, we hydrolyzed the glycoproteins in saliva and quantified the obtained free sugars (fucose, mannose, galactose, glucosamine, and galactosamine) by using high-performance anion-exchange chromatography with pulsed-amperometric detection (HPAEC-PAD). The glycosidic profiles were compared by using multivariate statistical analysis, showing differential glycosylation patterns among the three categories. Furthermore, ROC analysis allowed obtaining a reliable and minimally invasive protocol able to discriminate between healthy and pathological subjects.

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“…1), whether the HIV-induced changes in the circulating glycome are linked to inflammaging and HIV-associated co-morbidities (during both viremic and ART-suppressed HIV infection) is less clear. Recently, plasma glycomic biomarkers were identified (using lectins) to predict HIV-associated cardiovascular events [95]. However, more work is needed in this direction.…”

Section: A) Chronic Inflammation Has Been Associated With Aberrant Igg Glycosylation Patterns and Is Prevalent In Hiv+ Individuals Despitmentioning

confidence: 99%

Breaking the Glyco-Code of HIV Persistence and Immunopathogenesis

et al. 2019

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Purpose of review: Glycoimmunology is an emerging field focused on understanding how immune responses are mediated by glycans (carbohydrates) and their interaction with glycanbinding proteins called lectins. How glycans influence immunological functions is increasingly well understood. In a parallel way, in the HIV field, it is increasingly understood how the host immune system controls HIV persistence and immunopathogenesis. However, what has mostly been overlooked, despite its potential for therapeutic applications, is the role that the host glycosylation machinery plays in modulating the persistence and immunopathogenesis of HIV.Here, we will survey four areas in which the links between glycan-lectin interactions and immunology, and between immunology and HIV are well described. For each area, we will describe these links and then delineate the opportunities for the HIV field in investigating potential interactions between glycoimmunology and HIV persistence/immunopathogenesis. Recent findings:Recent studies show that the human glycome (the repertoire of human glycan structures) plays critical roles in driving or modulating several cellular processes and immunological functions that are central to maintaining HIV infection.

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Plasma glycomics predict cardiovascular disease in patients with ART‐controlled HIV infections

Cited by 11 publications

References 36 publications

Plasma ST6Gal1 is Dispensable for IgG Sialylation

Plasma ST6Gal1 is Dispensable for IgG Sialylation

Differential Glycosylation Levels in Saliva from Patients with Lung or Breast Cancer: A Preliminary Assessment for Early Diagnostic Purposes

Breaking the Glyco-Code of HIV Persistence and Immunopathogenesis

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