Caveats in Carbohydrate-deficient Transferrin Determination

Carbohydrate-deficient transferrin (CDT) refers to a group of minor isoforms of transferrin that, according to most authors, includes asialo-, monosialo-, and disialo-Fe2-transferrin (1). CDT is a widely used marker of chronic alcohol abuse in Europe and, after its recent approval by the Food and Drug Administration, a candidate to become a popular diagnostic tool in the US (2). Arndt (1) recently concluded that “CDT is the most specific marker of chronic alcohol abuse to date”. Its specificity, however, is affected by the choice of analytical method, which must selectively determine only the CDT components, without interference from the other transferrin glycoforms (trisialo-, tetrasialo-, pentasialo-, and hexasialo-Fe2-transferrin), which are present in large excess. Interference from trisialo-Fe2-transferrin has been reported for most commercial CDT tests, which are based on anion-exchange microchromatographic separations followed by immunoassays. Unfortunately, much of the literature does not report any correlation between trisialo-transferrin and alcohol intake (3). Moreover, Dibbelt (4) recently demonstrated by HPLC that increased relative concentrations of disialo- and asialo-transferrin associated with alcohol abuse are not correlated with increased trisialo-transferrin concentrations and consequently stated that “trisialo-transferrin is obviously of no diagnostic value, I strongly recommend not including this isotransferrin in the CDT fraction measured for laboratory diagnosis of alcoholism”.