Immunoglobulins are the major glycoproteins involved in the modifications of total serum N-glycome in cirrhotic patients

Purpose: N-glycosylation modifications in human serum glycoproteins have been described in hepatic cirrhosis. To identify the glycoproteins carrying these modifications and to determine their influences in the modification of the total serum N-glycome (TSNG) in cirrhotic patients, we have performed the glycosylation analysis of immunoglobulins, transferrin, 1 antitrypsin and haptoglobin of patients who have developed cirrhosis. Experimental design: The glycosylation analysis of immunoglobulins G, transferrin, 1 antitrypsin and haptoglobin of 14 patients who have developed cirrhosis and 11 healthy controls was performed using strategies based on MS, 2-DE and affinity chromatography. Results: We demonstrated that the N-glycosylation of both hepatic and plasma cell secreted glycoproteins is modified, and that the major modifications of TSNG are carried by immunoglobulins A and G. Conclusions and clinical Relevance: The search for glycomic biomarkers used as an alternative to liver biopsy for the assessment of fibrosis in chronic liver disease is extremely important. Variations in the glycosylation of immunoglobulins are responsible for the main modifications affecting the TSNG and effector properties of the Fc of these molecules, and certainly contribute to the pathophysiology of fibrosis.