Abstract
Mass spectrometric glycomics was used as an innovative approach to identify biomarkers in serum and dialysate samples from peritoneal dialysis (PD) patients. PD is a life-saving treatment worldwide applied in more than 100,000 patients suffering from chronic kidney disease. PD treatment uses the peritoneum as a natural membrane to exchange waste products from blood to a glucose-based solution. Daily exposure of the peritoneal membrane to these solutions may cause complications such as peritonitis, fibrosis and inflammation which, in the long term, lead to the failure of the treatment. It has been shown in the last years that protein N-glycosylation is related to inflammatory and fibrotic processes. Here, by using a recently developed MALDI-TOF-MS method with linkage-specific sialic acid derivatisation, we showed that alpha2,6-sialylation, especially in triantennary N-glycans from peritoneal effluents, is associated with critical clinical outcomes in a prospective cohort of 94 PD patients. Moreover, we found an association between the levels of presumably immunoglobulin-G-related glycans as well as galactosylation of diantennary glycans with PD-related complications such as peritonitis and loss of peritoneal mesothelial cell mass. The observed glycomic changes point to changes in protein abundance and protein-specific glycosylation, representing candidate functional biomarkers of PD and associated complications.
Highlights
A negative association was found for the relative galactosylation (A2G) and α2,6-sialylation (A2E) of diantennary glycans. These associations are in line with the trends we observed towards study end, i.e. increasing A2F, IgG-glycans, A3E, and decreasing A2G and A2E (Fig. 3A)
This strengthens the hypothesis that these N-glycan traits may reflect local peritoneal inflammation in PD patients, in particular, when assessed in PDE, since derived glycan traits in serum were not associated with peritonitis
When analysing a subselection of direct traits based on our findings for baseline and longitudinal glycan data, we found no association of selected triantennary α2,6-sialylated traits with peritonitis
Summary
Received: 19 April 2017 Accepted: 22 December 2017 Published: xx xx xxxx membrane transport characteristics in peritoneal dialysis patients. Exposure of the peritoneal membrane to these solutions may cause complications such as peritonitis, fibrosis and inflammation which, in the long term, lead to the failure of the treatment It has been shown in the last years that protein N-glycosylation is related to inflammatory and fibrotic processes. Long term exposure to PD solutions is associated with functional and structural alterations of the peritoneum which include neovascularisation, thickening of the peritoneal membrane, peritonitis[2,3,4] as well as epithelial-to-mesenchymal transition (EMT) The latter is known as a process whereby the mesothelial cells lining the peritoneal cavity lose their epithelial characteristics to acquire a fibroblast-like phenotype[5,6]. We present a novel and attractive approach for biomarker identification and demonstrate that changes in the glycosylation profile are associated with PD-related complications such as peritonitis, inflammation and mesothelial cell loss in a prospective cohort of 94 PD patients
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