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Articles |
Department of Clinical Neuroscience, Sections of
1
Clinical Alcohol and Drug Addiction Research and
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Neurology, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
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Department of Clinical Chemistry, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
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Department of Clinical Chemistry, Malmö University Hospital, SE-205 02 Malmö, Sweden.
aAddress correspondence to this author at: Alcohol Laboratory, L7:03, Karolinska Hospital, SE-171 76 Stockholm, Sweden. Fax 46-8-5177-1532; e-mail anders.helander{at}cspo.sll.se
Background: Isoforms of transferrin interfere with measurement of carbohydrate-deficient transferrin (CDT) as a marker of heavy alcohol consumption. We evaluated the rate of inaccurate CDT results by immunoassays.
Methods: We studied 2360 consecutive sera (1614 individuals) submitted for CDT assay without clinical information as well as samples from 1 patient with a congenital disorder of glycosylation (CDG Ia) and from 6 healthy carriers of CDG Ia. The CDTect, %CDT-TIA, and new %CDT immunoassays were compared with HPLC (%CDT-HPLC). Transferrin isoform pattern were evaluated by isoelectric focusing (IEF).
Results: Transferrin BC and CD heterozygotes were found at frequencies of 
0.7% and 0.2%, respectively. Another transferrin C subtype, where di- and trisialotransferrin partly coeluted (tentatively identified as C2C3), was observed in 0.6%. Compared with the %CDT-HPLC method, the immunoassays often produced low results for transferrin BC and high results for transferrin CD and "C2C3". A very high trisialotransferrin value (frequency 1%) often produced high CDT immunoassay results. In four of six healthy carriers of CDG Ia, a- and disialotransferrin were highly increased and the HPLC and IEF isoform patterns were indistinguishable from those in alcohol abuse.
Conclusions: Rare transferrin isoform types and abnormal amounts of trisialotransferrin (total frequency 2–3%) may cause incorrect determination of CDT with immunoassays. The observed variants were readily identified by HPLC and IEF, which can be recommended for verification of CDT immunoassay results in doubtful cases. In healthy carriers of CDG Ia, CDT is high by all assays.
The following articles in journals at HighWire Press have cited this article:
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  J. P. Bergstrom and A. Helander Clinical Characteristics of Carbohydrate-Deficient Transferrin (%Disialotransferrin) Measured by HPLC: Sensitivity, Specificity, Gender Effects, and Relationship with other Alcohol Biomarkers Alcohol Alcohol., July 1, 2008; 43(4): 436 - 441. [Abstract] [Full Text] [PDF]
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 J. B. Whitfield, V. Dy, P. A.F. Madden, A. C. Heath, N. G. Martin, and G. W. Montgomery Measuring Carbohydrate-Deficient Transferrin by Direct Immunoassay: Factors Affecting Diagnostic Sensitivity for Excessive Alcohol Intake Clin. Chem., July 1, 2008; 54(7): 1158 - 1165. [Abstract] [Full Text] [PDF]
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A. Helander and G. Nordin Insufficient Standardization of a Direct Carbohydrate-Deficient Transferrin Immunoassay Clin. Chem., June 1, 2008; 54(6): 1090 - 1092. [Full Text] [PDF]
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J. R. Delanghe, A. Helander, J. P.M. Wielders, J. M. Pekelharing, H. J. Roth, F. Schellenberg, C. Born, E. Yagmur, W. Gentzer, and H. Althaus Development and Multicenter Evaluation of the N Latex CDT Direct Immunonephelometric Assay for Serum Carbohydrate-Deficient Transferrin Clin. Chem., June 1, 2007; 53(6): 1115 - 1121. [Abstract] [Full Text] [PDF]
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F. Bortolotti, G. De Paoli, J. P. Pascali, M. T. Trevisan, M. Floreani, and F. Tagliaro Analysis of Carbohydrate-Deficient Transferrin: Comparative Evaluation of Turbidimetric Immunoassay, Capillary Zone Electrophoresis, and HPLC Clin. Chem., December 1, 2005; 51(12): 2368 - 2371. [Full Text] [PDF]
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B. M.R. Appenzeller and R. Wennig Altered Distribution of Transferrin Isoforms According to Serum Storage Conditions Clin. Chem., November 1, 2005; 51(11): 2159 - 2162. [Full Text] [PDF]
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A. Helander, J. P.M. Wielders, R. te Stroet, and J. P. Bergstrom Comparison of HPLC and Capillary Electrophoresis for Confirmatory Testing of the Alcohol Misuse Marker Carbohydrate-Deficient Transferrin Clin. Chem., August 1, 2005; 51(8): 1528 - 1531. [Full Text] [PDF]
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A. Helander, J. Bergstrom, and H. H. Freeze Testing for Congenital Disorders of Glycosylation by HPLC Measurement of Serum Transferrin Glycoforms Clin. Chem., May 1, 2004; 50(5): 954 - 958. [Full Text] [PDF]
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P. Anttila, K. Jarvi, J. Latvala, and O. Niemela METHOD-DEPENDENT CHARACTERISTICS OF CARBOHYDRATE-DEFICIENT TRANSFERRIN MEASUREMENTS IN THE FOLLOW-UP OF ALCOHOLICS Alcohol Alcohol., January 1, 2004; 39(1): 59 - 63. [Abstract] [Full Text] [PDF]
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B. Ramdani, V. Nuyens, T. Codden, G. Perpete, J. Colicis, A. Lenaerts, J.-P. Henry, and F. J. Legros Analyte Comigrating with Trisialotransferrin during Capillary Zone Electrophoresis of Sera from Patients with Cancer Clin. Chem., November 1, 2003; 49(11): 1854 - 1864. [Abstract] [Full Text] [PDF]
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A. Helander, A. Husa, and J.-O. Jeppsson Improved HPLC Method for Carbohydrate-deficient Transferrin in Serum Clin. Chem., November 1, 2003; 49(11): 1881 - 1890. [Abstract] [Full Text] [PDF]
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P. Anttila, K. Jarvi, J. Latvala, J. E. Blake, and O. Niemela DIAGNOSTIC CHARACTERISTICS OF DIFFERENT CARBOHYDRATE-DEFICIENT TRANSFERRIN METHODS IN THE DETECTION OF PROBLEM DRINKING: EFFECTS OF LIVER DISEASE AND ALCOHOL CONSUMPTION Alcohol Alcohol., September 1, 2003; 38(5): 415 - 420. [Abstract] [Full Text] [PDF]
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M. J. Schwarz, I. Domke, A. Helander, P. M. W. Janssens, J. van Pelt, B. Springer, M. Ackenheil, K. Bernhardt, G. Weigl, and M. Soyka MULTICENTRE EVALUATION OF A NEW ASSAY FOR DETERMINATION OF CARBOHYDRATE-DEFICIENT TRANSFERRIN Alcohol Alcohol., May 1, 2003; 38(3): 270 - 275. [Abstract] [Full Text] [PDF]
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 N. Callewaert, E. Schollen, A. Vanhecke, J. Jaeken, G. Matthijs, and R. Contreras Increased fucosylation and reduced branching of serum glycoprotein N-glycans in all known subtypes of congenital disorder of glycosylation I Glycobiology, May 1, 2003; 13(5): 367 - 375. [Abstract] [Full Text] [PDF]
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F. J. Legros, V. Nuyens, M. Baudoux, K. Zouaoui Boudjeltia, J.-L. Ruelle, J. Colicis, F. Cantraine, and J.-P. Henry Use of Capillary Zone Electrophoresis for Differentiating Excessive from Moderate Alcohol Consumption Clin. Chem., March 1, 2003; 49(3): 440 - 449. [Abstract] [Full Text] [PDF]
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F. J. Legros, V. Nuyens, E. Minet, P. Emonts, K. Z. Boudjeltia, A. Courbe, J.-L. Ruelle, J. Colicis, F. de L'Escaille, and J.-P. Henry Carbohydrate-deficient Transferrin Isoforms Measured by Capillary Zone Electrophoresis for Detection of Alcohol Abuse Clin. Chem., December 1, 2002; 48(12): 2177 - 2186. [Abstract] [Full Text] [PDF]
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 H. Ueda, H. Matsumoto, N. Takahashi, and H. Ogawa Psathyrella velutina Mushroom Lectin Exhibits High Affinity toward Sialoglycoproteins Possessing Terminal N-Acetylneuraminic Acid alpha 2,3-Linked to Penultimate Galactose Residues of Trisialyl N-Glycans. COMPARISON WITH OTHER SIALIC ACID-SPECIFIC LECTINS J. Biol. Chem., July 5, 2002; 277(28): 24916 - 24925. [Abstract] [Full Text] [PDF]
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F. Tagliaro, F. Bortolotti, R. M. Dorizzi, M. Marigo, J. R. Delanghe, B. Wuyts, and M. L. De Buyzere Caveats in Carbohydrate-deficient Transferrin Determination Drs. Delanghe, Wuyts, and De Buyzere respond: Clin. Chem., January 1, 2002; 48(1): 208 - 209. [Full Text] [PDF]
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A. Helander, M. Fors, and B. Zakrisson STUDY OF AXIS-SHIELD NEW %CDT IMMUNOASSAY FOR QUANTIFICATION OF CARBOHYDRATE-DEFICIENT TRANSFERRIN (CDT) IN SERUM Alcohol Alcohol., September 1, 2001; 36(5): 406 - 412. [Abstract] [Full Text] [PDF]
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