Desialotransferrin

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Desialo (DST) ( English : Carbohydrate-Deficient-transferrin, CDT to German : Kohlenhydratdefizientes transferrin ) is a variant of the glycoprotein transferrin , which in every human serum occurs and plays an important role as an iron transport protein. Desialotransferrin serves as a biomarker for the diagnosis of alcohol consumption. The use as a laboratory marker for alcohol intake is prone to failure, e.g. B. with increased gamma GT value .

Occurrence

As a glycoprotein, the transferrin molecule carries carbohydrate side chains in several places that have sialic acid residues . Transferrin isoforms with two (di-sialotransferrin) to six (hexa-sialotransferrin) sialic acid residues are normally found in human blood. Tetra-sialotransferrin (four sialic acid residues) normally makes up the majority.

There are also genetically determined transferrin variants.

Changes in alcohol intake

The structure of the transferrins is typically changed with increasing alcohol consumption. There is predominantly an increased loss of entire carbohydrate side chains. Here, the transfer of the high-mannose carbohydrate chain precursor, which is bound to dolichol phosphate, is disturbed, although the exact pathomechanism has not yet been clarified. Excessive and prolonged consumption of alcohol also changes the various glycosyltransferases, which further changes the carbohydrate chains. Due to this change in the glycosylation pattern (carbohydrate pattern), the CDT concentration rises sharply (normal value for men approx. 20 U / l, women 26 U / l, increases from 30 to> 60 U / l). This increases the relative proportion of di-, mono- and A-sialotransferrin (two, one or no side chains). The sum of these proportions of transferrins is called CDT.

CDT as a laboratory parameter

CDT can be used as a laboratory parameter to diagnose alcohol disease (or to prove alcohol abuse). Increased CDT values ​​are found after consuming more than 60 g alcohol (ethanol) per day for at least one week, which corresponds to approx. 0.7 l of wine or approx. 1.5 l of beer. Even after abstinence from alcohol, the values ​​remain elevated for some time (two to four weeks) with a half-life of 14 to 17 days. CDT is said to have a sensitivity of 81 to 93% and a specificity of 98%. However, even in 2001, despite decades of popularity, doubts about the validity of the method were expressed in a review and the necessary basic research was called for.

When assessing and comparing CDT measurement results, it should be noted that each measurement method has different normal ranges and that each measured value must therefore be assessed in relation to its normal range. The percentage of CDT in relation to total transferrin is used as a relative unit of measurement. Reference values ​​measured with HPLC are below 1.75% (BIO-RAD test: below 2.6%). Men who consume over 60 g / day of alcohol for at least three weeks (women over 50 g / day for two weeks) can achieve a CDT percentage of up to 18%.

The determination of the CDT value is indicated in the following cases:

  • Differential diagnosis of alcohol-induced versus non-alcohol-induced diseases (pancreatitis, liver cirrhosis, carcinoma, gastritis)
  • Differential diagnosis in the case of increased GGT values
  • Re -issue of the driving license in accordance with the driving license regulation
  • Forensic-toxicological assessment of accidents and deaths in connection with alcohol

Analytics

For laboratory analysis , various methods are used: HPLC (high performance liquid chromatography), anion exchange column chromatography with immunological transferrin determination, IEF ( isoelectric focusing ), capillary electrophoresis and antibody-based detection of asialo forms. The determination of the quotient of transferrin and CDT via the coupling of HPLC and mass spectrometry allows the most meaningful detection of carbohydrate deficient transferrin (FDA standard).

The HPLC and capillary electrophoresis allows the quantification of individual fractions and the detection of genetic variants. IEF is the method with the highest selectivity, but does not allow reliable quantification. In the case of anion exchange column chromatography with immunological transferrin determination (BIO-RAD method), genetic variants cannot in principle be recognized. Positive (pathological) findings must therefore be confirmed by another method (e.g. HPLC ).

literature

  • Manfred V. Singer, Kamayni Agarwal-Kozlowski, Stephan Teyssen, Alexander Schneider: Basics of alcohol and alcohol- related diseases , diagnostics, therapy . Springer, Heidelberg 2005, ISBN 3-540-22552-8 , pp. 413 ff .
  • Manfred V. Singer, S. Teyssen (Ed.): Compendium alcohol . Springer, Berlin 2002, ISBN 3-540-41312-X , p. 119 .
  • ML Hannuksela, MK Liisanantti et al: Biochemical markers of alcoholism. In: Clinical chemistry and laboratory medicine: CCLM / FESCC Volume 45, Number 8, 2007, pp. 953-961. doi: 10.1515 / CCLM.2007.190 . PMID 17579567 . (Review).
  • F. Bortolotti, G. De Paoli, F. Tagliaro: Carbohydrate-deficient transferrin (CDT) as a marker of alcohol abuse: a critical review of the literature 2001-2005. In: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Volume 841, Numbers 1-2, September 2006, pp. 96-109. doi: 10.1016 / j.jchromb.2006.05.005 . PMID 16725384 . (Review).
  • F. Tagliaro, J. Pascali et al. a .: Recent advances in the application of CE to forensic sciences: an update over years 2007-2009. In: Electrophoresis Volume 31, Number 1, January 2010, pp. 251-259. doi: 10.1002 / elps.200900482 . PMID 19950357 . (Review).

Individual evidence

  1. ↑ PC Sharpe: Biochemical detection and monitoring of alcohol abuse and abstinence . In: Ann. Clin. Biochem. tape 38 , no. 6 , November 2001, p. 652-664 , doi : 10.1258 / 0004563011901064 , PMID 11732647 .
  2. ↑ The drug affinity of young people in the Federal Republic of Germany in 2008 ( Memento of the original from March 4, 2016 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. from the Federal Center for Health Education, October 2008.  @1@ 2Template: Webachiv / IABot / www.uni-due.de
  3. ↑ How to calculate the amount of alcohol in grams
  4. ↑ A. Helander, M. Fors, B. Zakrisson: Alcohol & Alcoholism (2001) 36 (5), pp. 406-412
  5. ↑ T. Arndt: Carbohydrate-deficient transferrin as a marker of chronic alcohol abuse: a critical review of preanalysis, analysis, and interpretation. In: Clinical chemistry Volume 47, Number 1, January 2001, pp. 13-27. PMID 11148172 . (Review).