OBJECTIVE: We have previously shown the potential of glycomics to distinguish patients with steatosis from patients with non-alcoholic steatohepatitis (NASH) in an adult population. The pattern of disease in paediatric patients is distinct from adults. The objective of this study was to characterize the N -glycomic profile of children with varying degrees of non-alcoholic fatty liver disease (NAFLD) and identify potential biomarker profiles of disease. METHODS: Serum protein N-glycosylation patterns of 51 paediatric NAFLD patients were assessed with deoxyribonucleic acid sequencer-assisted fluorophore-assisted capillary electrophoresis and compared with histology. RESULTS: Peak 1 (NGA2F) is the most significantly elevated N-glycan in paediatric NASH patients with peak 5 (NA2) demonstrating the largest decrease. The logarithmically transformed ratio of peak 1 to peak 5 was -0.85 (standard deviation [SD] 0.22) in patients with steatosis and borderline NASH and -0.73 (SD 0.12) in NASH (P = 0.02). The biomarker correlated well with the amount of lobular inflammation with a consistent increase of marker score in ascending stage of lobular inflammation. There was also a trend in differentiating patients with significant fibrosis ≥F2; -0.74 (SD 0.13) from patients with no/minimal fibrosis <F2; -0.86 (SD 0.24), P = 0.06. Analysis of the N-glycans on immunoglobulin G confirmed the undergalactosylation status typical for chronic inflammatory conditions. CONCLUSIONS: This study is the first glycomic analysis performed in a paediatric NAFLD population. In agreement with the results obtained in adults, B cells play a dominant role in the N-glycan alterations of paediatric NASH patients.
OBJECTIVE: We have previously shown the potential of glycomics to distinguish patients with steatosis from patients with non-alcoholic steatohepatitis (NASH) in an adult population. The pattern of disease in paediatric patients is distinct from adults. The objective of this study was to characterize the N -glycomic profile of children with varying degrees of non-alcoholic fatty liver disease (NAFLD) and identify potential biomarker profiles of disease. METHODS: Serum protein N-glycosylation patterns of 51 paediatric NAFLD patients were assessed with deoxyribonucleic acid sequencer-assisted fluorophore-assisted capillary electrophoresis and compared with histology. RESULTS:Peak 1 (NGA2F) is the most significantly elevated N-glycan in paediatric NASH patients with peak 5 (NA2) demonstrating the largest decrease. The logarithmically transformed ratio of peak 1 to peak 5 was -0.85 (standard deviation [SD] 0.22) in patients with steatosis and borderline NASH and -0.73 (SD 0.12) in NASH (P = 0.02). The biomarker correlated well with the amount of lobular inflammation with a consistent increase of marker score in ascending stage of lobular inflammation. There was also a trend in differentiating patients with significant fibrosis ≥F2; -0.74 (SD 0.13) from patients with no/minimal fibrosis <F2; -0.86 (SD 0.24), P = 0.06. Analysis of the N-glycans on immunoglobulin G confirmed the undergalactosylation status typical for chronic inflammatory conditions. CONCLUSIONS: This study is the first glycomic analysis performed in a paediatric NAFLD population. In agreement with the results obtained in adults, B cells play a dominant role in the N-glycan alterations of paediatric NASH patients.
Authors: Simona Riccio; Rosa Melone; Caterina Vitulano; Pierfrancesco Guida; Ivan Maddaluno; Stefano Guarino; Pierluigi Marzuillo; Emanuele Miraglia Del Giudice; Anna Di Sessa Journal: World J Clin Pediatr Date: 2022-03-23
Authors: Claudio Franceschi; Paolo Garagnani; Cristina Morsiani; Maria Conte; Aurelia Santoro; Andrea Grignolio; Daniela Monti; Miriam Capri; Stefano Salvioli Journal: Front Med (Lausanne) Date: 2018-03-12