Changed Profile of Serum Transferrin Isoforms in Primary Biliary Cholangitis

Abstract

Liver damage affects the synthesis of proteins and glycoproteins, and alters their posttranslational modification, such as glycosylation changing the serum profile of glycoprotein isoforms. The retention of hydrophobic bile acids in the course of cholestatic liver diseases is a major cause of liver damage in primary biliary cholangitis (PBC). The study objective was to determine the serum profile of transferrin isoforms in primary biliary cholangitis and compare it to transferrin isoforms profile in extrahepatic cholestasis. The study was carried out in 76 patients with PBC and 40 healthy blood donors. Transferrin isoforms were analyzed by the capillary electrophoresis method. The mean relative concentrations of disialotransferrin and trisialotransferrin in PBC were significantly lower than those in the healthy subjects (p < 0.001, p = 0.011; respectively). None of the transferrin isoforms changed according to the disease severity evaluated by the Ludwig scoring system. However, the disease stage affected the activity of alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT), and albumin level (p = 0.002; p = 0.013 and p = 0.005, respectively). Our results indicate that serum profile of transferrin isoforms alters primary biliary cholangitis and differs in comparison to transferrin isoforms profile in extrahepatic cholestasis. The decreased concentrations of lower sialylated isoforms of transferrin (low percentage share in total transferrin level) are not associated with the histological stage of disease.

The Association of Serum Profile of Transferrin Isoforms with COVID-19 Disease Severity

“…The persistent changes in the total concentration of transferrin can be explained by the half-life of transferrin in the blood, which is 14 days and is longer than the time interval between the 1st and 2nd collection of the material for the study (an average of 9 days). Our previous research indicates that the altered serum profile of transferrin isoforms may be pathognomonic for a particular disease [16][17][18][19], and so, in patients with chronic hepatitis, the tetrasialotransferrin level was increased and the pentasialotransferrin level decreased [16]. Additionally, in rheumatoid arthiritis patients, there was a significant decrease in the relative concentrations of trisialo-and pentasialotransferrin and a significant increase in tetrasialotransferrin [17].…”

“…Based on this information, and the importance of transferrin isoforms in delivering oxygen to the tissues through its involvement in iron metabolism [12], the aim of this study was to evaluate the association of the serum profile of transferrin isoforms with the severity of COVID-19 disease (i.e., COVID-19 severity scale of World Health Organization, presence of cytokine storm, oxygen therapy and chronic disease, the value of modifited early worning score-MEWS) and to compare this profile to the profiles in other diseases. Based on our previous research, we have grounds to assume that the profile of TRF isoforms in COVID-19 disease will differ from profiles in other clinical situations [16][17][18][19], which creates the possibility of using this study for clinical (diagnostic) purposes. Jena GmbH, Jena, Germany).…”

The Serum Profile of Transferrin Isoforms in Pancreatitis

“…In this paper, we tried to determine the profile of transferrin isoforms in pancreatitis, in acute as well as in chronic forms of disease, in accordance with the knowledge on the changes of protein glycosylation in the course of inflammatory diseases. Because we previously assessed the profile of transferrin isoforms in many different diseases, including liver diseases, rheumatic diseases and pancreatic cancers, we have the opportunity to compare the changes in pancreatitis with the changes in the diseases mentioned above [ 6 , 10 , 11 , 13 ]. This situation created the possibility to show whether these changes are characteristic for pancreatitis or only organ-dependent inflammation.…”

“…In this study, we determine the profile of transferrin isoforms by means of the capillary electrophoresis method, which enables the determination of five different isoforms (asialo-, disialo-, trisialo-, tetrasialo- and pentasialo-transferrin) [ 8 ]. We expect to obtain the characteristic profile of Tf isoforms, which is different from that in pancreatic cancers [ 6 ], liver [ 9 , 10 ] and rheumatic diseases [ 11 , 12 ].…”

Pediatric Liver Disease Patients and Secondary Glycosylation Abnormalities

“…Transferrin is the iron-binding serum glycoprotein which is produced in hepatocytes and contains two N-linked glycosylation sites (4,5). An abnormal glycosylation is also a known phenomenon in liver disease patients; it has been described in alcoholic liver disease (decreased enzyme activities of mannosyltransferase and galactosyltransferase, lowered intracellular dolichol concentration, desialylation of serum Tf, α1-antitrypsin and ceruloplasmin; hyperfucosylation of haptoglobin and serum Tf), galactosemia and fructosemia (the pattern resembling CDG type I), chronic hepatitis B and C, non-alcoholic steatohepatitis, and bile-related liver diseases (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Despite of IEF, there are also some other methods, like HPLC or MALDI-TOF but they are not available in Poland.…”