Symposium 12 Monday Sept. 24th 9 am–10.30 am; Room: Lecture Hall 4
Focus on CDT—measurement standardization and clinical application: Chairpersons: Helander A, Sweden Neumann T (Germany)
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Presentation S12-1
The past, present and future of carbohydrate-deficient transferrin (CDT) as alcohol biomarker
Helander A (Sweden)
Aims. Carbohydrate-deficient transferrin (CDT) refers to alcohol-induced changes in the carbohydrate composition of the iron-transport glycoprotein transferrin. CDT is used as a biomarker to identify heavy alcohol consumption and to monitor abstinence during treatment. This presentation gives a brief overview of the history of CDT testing, from the initial studies until the ongoing standardisation process.
Methods. In the 1970s, an abnormal transferrin microheterogeneity related to alcohol abuse was identified in serum and CSF by IEF technique. The alcohol-associated glycoforms showed a reduced sialic acid content compared with the major tetrasialotransferrin glycoform; hence the name ‘carbohydrate-deficient’ transferrin. CDT was originally defined as the sum of asialo-, monosialo- and disialotransferrin. Later studies revealed that disialo- and asialotransferrin were the main alcohol-related glycoforms, missing one complete N-glycan (disialotransferrin) or both N-glycans (asialotransferrin).
Results. Several analytical methods have been applied for CDT. They have covered different glycoforms as CDT, and given the content in various absolute or relative amounts, which has complicated the comparability of results. The normalisation of CDT values to the total transferrin concentration contributed to a significant improvement in test specificity. Another important step is the current standardisation process that aims to define the most appropriate CDT analyte, and select and validate a reference method and reference materials.
Conclusions. The main asset of CDT compared with conventional alcohol tests such as GGT and MCV is its high specificity for heavy drinking with resulting low rate of false-positive identifications. The standardisation work will further improve the diagnostic performance of CDT as an alcohol biomarker.
Presentation S12-2
Determination of carbohydrate deficient transferrin in human serum by capillary zone electrophoresis
Thormann W, Lanz C, Marti U (Switzerland)
Aims. During the past 20 years, various analytical methods for the determination of carbohydrate-deficient transferrin (CDT) in human serum have been developed, including isoelectric focusing, immunochemical determinations after anion exchange chromatography, high performance liquid chromatography (HPLC) and capillary zone electrophoresis (CZE). This contribution discusses the principles, available assays and pros and cons of CZE. Using CZE assays, the various isoforms of transferrin, including asialo-, disialo-, trisialo-, tetrasialo- and pentasialo-transferrin, are separated and quantitated within a few minutes and without elaborate sample pretreatment. Transferrin peaks can be identified via detection times and, if necessary, immunosubtraction. CZE represents an attractive alternative to HPLC. It features simpler sample preparation, faster analysis time and higher isoform resolution compared to the most recent HPLC approaches and can thus be regarded as a new candidate of a reference method for CDT. The CZE assays are robust and suitable for routine CDT screening and confirmation analysis. For quite some time, our laboratories have been engaged in studying and optimizing CZE methods for analysis of CDT and are using this technology routinely for patient screening and confirmation analysis. Data obtained on Beckman Coulter and Sebia instrumentation are presented and compared.
This work was supported by Analis, Suarlée, Belgium, by the Liver Foundation, Bern, Switzerland and by the Swiss National Science Foundation.
Presentation S12-3
Application of CDT in traffic medicine
Bortolotti F, Tagliaro F (Italy)
Aims. In several European countries, CDT has been included in the panels of tests required to check the physical fitness for issuing of driving license. However, so far, no widely tested proof has been given of a significance of increased CDT levels in terms of increased risk of driving while intoxicated (DWI). The aim of the present work was to identify an association between conditions of DWI and elevated CDT concentrations.
Methods. Group A was composed of 40 adult male subjects, stopped by the police for dangerous driving or for being involved in traffic accidents, whose blood alcohol concentrations ranged from 1.00 to 4.21 g/l. Group B was composed of 51 male subjects, randomly chosen from the general population. Sera from both groups underwent CDT determination by using capillary electrophoresis.
Results. In group A and in group B, CDT index ranged from 0.79% to 15.86% and from 0.53% to 2.24, respectively. CDT results from both groups were classified as ‘negative’ or ‘positive’ on the basis of the cut off value (2.00%). The subjects classified as ‘positive’ in group A were 27 (67.5%), whereas in group B were 2. The subjects classified as ‘negative’ in group A were 13 (32.5%), whereas in group B were 49 (96.1%). The comparison of the observed percentages, evaluated with chi squared test, was highly significant (P < 0.001).
Conclusions. The data confirm that CDT is a biomarker suitable for application in a traffic safety context, as elevated CDT concentrations can indirectly be associated with increased risk of driving under the influence.
Presentation S12-4
Application of CDT in emergency or operative medicine
Neumann T, Kork F, Spies C (Germany)
The rate of the patients seen in surgical settings with alcohol use-related disorders (AUD) varies and might be up to 50% in trauma settings or in surgical units involved in care the cancer of the aerodigestive tract. An early and exact diagnosis is mandatory, because these patients are endangered by an increased perioperative or posttraumatic risk for morbidity compared to non at-risk-drinking controls. A variety of treatment options and preventive means are effective to reduce morbidity. For screening purposes the use of biomarkers is recommended next to past medical history and questionnaires. CDT has been shown to be a sensitive and specific marker for the detection of long term chronic heavy drinking; however sensitivity decreases, when the rate of young, hazardous, non-continuous, low level, binge pattern consumers is considerable. The administration of larger amounts of fluid (e.g. volume resuscitation) might also decrease sensitivity. CDT has been helpful to identify patients at risk for posttraumatic and postoperative complications. The most prominent advantage of markers such as CDT is the ability to identify candidates for preventive procedures in patient groups who can not provide verbal information. It might also be helpful to detect underreporting.