Strategies To Study Human Serum Transferrin Isoforms Using Integrated Liquid Chromatography ICPMS, MALDI-TOF, and ESI-Q-TOF Detection:  Application to Chronic Alcohol Abuse

2005 ◽  
Vol 77 (17) ◽  
pp. 5615-5621 ◽  
Author(s):  
M. Estela del Castillo Busto ◽  
Maria Montes-Bayón ◽  
Elisa Blanco-González ◽  
Juris Meija ◽  
Alfredo Sanz-Medel
1999 ◽  
Vol 45 (9) ◽  
pp. 1408-1413 ◽  
Author(s):  
Hugues Henry ◽  
Florian Froehlich ◽  
Renaud Perret ◽  
Jean-Daniel Tissot ◽  
Barbara Eilers-Messerli ◽  
...  

Abstract Background: Chronic alcohol abuse alters the normal N-glycosylation of transferrin, producing the carbohydrate-deficient transferrin isoforms. This alteration could be similar to that present in patients with carbohydrate-deficient glycoprotein syndrome type 1 (CDG1). We thus compared the alterations of N-glycans present in patients with alcoholism and patients with CDG1. Methods: The N-glycans of serum glycoproteins were compared in sera of patients with alcoholism, patients with CDG1, and controls by two-dimensional electrophoresis, neuraminidase, peptide:N-glycosidase F, and endoglycosidase F2 treatments. A specific antibody directed against the amino acid sequence surrounding the N-432 N-glycosylation site of transferrin was prepared (SZ-350 antibody). Results: In patients with alcoholism, the abnormal transferrin and α1-antitrypsin isoforms were devoid of a variable number of entire N-glycan moieties and were identical with those present in CDG1. In the serum of patients with alcoholism, this finding was less pronounced than in CDG1. In contrast to CDG1, there was no decrease in clusterin or serum amyloid P in patients with alcoholism. The SZ-350 antibody recognized only transferrin isoforms with one or no N-glycan moieties. Conclusion: Antibodies directed against specific N-glycosylation sites of glycoproteins could be useful for developing more specific immunochemical tests for the diagnosis of chronic alcohol abuse.


2001 ◽  
Vol 47 (1) ◽  
pp. 13-27 ◽  
Author(s):  
Torsten Arndt

Abstract Background: Carbohydrate-deficient transferrin (CDT) is used for diagnosis of chronic alcohol abuse. Some 200–300 reports on CDT have been published in impact factor-listed journals. The aims of this review were to condense the current knowledge and to resolve remaining issues on CDT. Approach: The literature (1976–2000) was searched using MEDLINE and Knowledge Server with “alcohol and CDT” as the search items. The data were reviewed systematically, checked for redundancy, and organized in sequence based on the steps involved in CDT analysis. Content: The review is divided into sections based on microheterogeneity of human serum transferrin (Tf), definition of CDT, structure of human serum CDT, pathomechanisms of ethanol-induced CDT increase, preanalysis, analysis, and medical interpretation (postanalysis). Test-specific cutoff values for serum CDT and causes of false positives and negatives for chronic alcohol abuse are discussed and summarized. Summary: Asialo- and disialo-Fe2-Tf, which lack one or two complete N-glycans, and monosialo-Fe2-Tf (structure remains unclear) are collectively referred to as CDT. Diminished mRNA concentration and glycoprotein glycosyltransferase activities involved in Tf N-glycan synthesis and increased sialidase activity most likely account for alcohol-induced increases in CDT. Knowledge about in vivo and in vitro effects on serum CDT is poor. Reliable CDT and non-CDT fractionation is needed for CDT measurement. Analysis methods with different analytical specificities and recoveries decreased the comparability of values and statistical parameters of the diagnostic efficiency of CDT. CDT is the most specific marker of chronic alcohol abuse to date. Efforts should concentrate on the pathomechanisms (in vivo), preanalysis, and standardization of CDT analysis.


2010 ◽  
Vol 29 (2) ◽  
pp. 95-101 ◽  
Author(s):  
Nebojša Maksić ◽  
Tatjana Vodnik ◽  
Maja Stanković ◽  
Srđan Milovanović ◽  
Ljubiša Radivojević ◽  
...  

Carbohydrate-Deficient Transferrin - A Contemporary Biomarker in Comparison with Traditional Laboratory Markers of Chronic Alcohol AbuseTimely identification of excessive alcohol use and its potential complications is a prerequisite for successful treatment. Several routine tests have been used in laboratories that may help in diagnosing alcoholism, such as determination of MCV, AST, ALT, GGT, but it has been shown that they lack specificity and sensitivity. Contemporary bio-markers are increasingly being used today that may due to their unique characteristics help in discovering the onset of chronic alcohol abuse, as well as in abstinence and relapse monitoring. The term carbohydrate-deficient transferrin (CDT) stands for a small group of human transferrin isoforms (asialo, monosialo, and disialotran sferrin) with a lower degree of glycosylation in comparison to the dominant transferrin isoform (tetrasialotransferrin). Persons consuming large quantities of alcohol (≥50-80 g daily) over a period of at least two weeks have increased concentrations of transferrin isoforms lacking one (disialotransferrin) or both (asialotransferrin) carbohydrate chains. In this paper the traditional markers of chronic alcohol abuse (GGT, AST, ALT, and MCV) were determined, as well as the new biomarker CDT, after which diagnostic evaluation was performed and their usability and clinical value in routine laboratory practice were estimated. These markers were also determined in heavy alcoholics on admission into hospital and after two weeks of therapy, with the aim of estimating their diagnostic value for abstinence and relapse monitoring.


RSC Advances ◽  
2020 ◽  
Vol 10 (58) ◽  
pp. 35574-35581
Author(s):  
Bryan Wang ◽  
Xuan Luo

Human-serum transferrin is involved in the transportation of aluminum across the blood–brain barrier.


1998 ◽  
Vol 22 (s5) ◽  
pp. 196S-200S ◽  
Author(s):  
George Fein ◽  
Daniel J. Fletcher ◽  
Victoria Sclafani

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