Heparan sulfate is a plasma biomarker of acute cellular allograft rejection

Barbas, Andrew S.; Lin, Li-Wen; McRae, MacKenzie; MacDonald, Andrea; Truong, Tracy; Yang, Yiping; Brennan, Todd V.

doi:10.1371/journal.pone.0200877

Cited by 10 publications

(13 citation statements)

References 33 publications

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“…A strong association between type 2 diabetes and viral infections using core proteins (syndecans, glypicans) as receptors has already been demonstrated (see Table 1 ), as has the degradation (in number) of HS chains during viral infections including HCMV [ 101 ], DENV [ 102 ], and HSV-1 [ 32 ]. The degradation of HS leads to overexpression of HPSE at the cell surface, which is observed during infection (see Section 4.4 ).…”

Section: Discussionmentioning

confidence: 99%

Antiviral strategies should focus on stimulating the biosynthesis of heparan sulfates, not their inhibition

Cheudjeu¹

2021

Life Sciences

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Antiviral strategies for viruses that utilize proteoglycan core proteins (syndecans and glypicans) as receptors should focus on heparan sulfate (HS) biosynthesis rather than on inhibition of these sugar chains. Here, we show that heparin and certain xylosides, which exhibit in vitro viral entry inhibitory properties against HSV-1, HSV-2, HPV-16, HPV-31, HVB, HVC, HIV-1, HTLV-1, SARS-CoV-2, HCMV, DENV-1, and DENV-2, stimulated HS biosynthesis at the cell surface 2- to 3-fold for heparin and up to 10-fold for such xylosides. This is consistent with the hypothesis from a previous study that for core protein attachment, viruses are glycosylated at HS attachment sites ( i.e. , serine residues intended to receive the D-xylose molecule for initiating HS chains). Heparanase overexpression, endocytic entry, and syndecan shedding enhancement, all of which are observed during viral infection, lead to glycocalyx deregulation and appear to be direct consequences of this hypothesis. In addition to the appearance of type 2 diabetes and the degradation of HS observed during viral infection, we linked this hypothesis to that proposed in a previous publication.

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Section: Discussionmentioning

confidence: 99%

Antiviral strategies should focus on stimulating the biosynthesis of heparan sulfates, not their inhibition

Cheudjeu¹

2021

Life Sciences

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“…Heparan Sulfate plasma levels are increased in TCMR compared to stable graft, due to release from EM during graft T-cell infiltration [ 2 , 139 ].…”

Section: Armentioning

confidence: 99%

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Quaglia

Merlotti

Guglielmetti

et al. 2020

IJMS

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New biomarkers of early and late graft dysfunction are needed in renal transplant to improve management of complications and prolong graft survival. A wide range of potential diagnostic and prognostic biomarkers, measured in different biological fluids (serum, plasma, urine) and in renal tissues, have been proposed for post-transplant delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction (CAD). This review investigates old and new potential biomarkers for each of these clinical domains, seeking to underline their limits and strengths. OMICs technology has allowed identifying many candidate biomarkers, providing diagnostic and prognostic information at very early stages of pathological processes, such as AR. Donor-derived cell-free DNA (ddcfDNA) and extracellular vesicles (EVs) are further promising tools. Although most of these biomarkers still need to be validated in multiple independent cohorts and standardized, they are paving the way for substantial advances, such as the possibility of accurately predicting risk of DGF before graft is implanted, of making a “molecular” diagnosis of subclinical rejection even before histological lesions develop, or of dissecting etiology of CAD. Identification of “immunoquiescent” or even tolerant patients to guide minimization of immunosuppressive therapy is another area of active research. The parallel progress in imaging techniques, bioinformatics, and artificial intelligence (AI) is helping to fully exploit the wealth of information provided by biomarkers, leading to improved disease nosology of old entities such as transplant glomerulopathy. Prospective studies are needed to assess whether introduction of these new sets of biomarkers into clinical practice could actually reduce the need for renal biopsy, integrate traditional tools, and ultimately improve graft survival compared to current management.

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“…19 At the clinical level, circulating HS concentrations were elevated in patients subjected to major liver resection with transient vascular inflow occlusion. 15 However, a similar increase in plasma HS was observed in a subgroup of patients that underwent major hepatic or other surgical procedures but without I/R 12,74,75 , suggesting that other mechanisms could alter the glycocalyx in hepatic microvascular endothelial cells. It should be emphasized that comparable puzzling observations were encountered in both CPB and after aortic clamping, in which increases in plasma HS and SYND-1 occurred regardless of the duration of ischemia.…”

Section: Pulmonary I/r Damagementioning

confidence: 73%