Immunonephelometric carbohydrate-deficient transferrin results and transferrin variants.

Carbohydrate-deficient transferrin (CDT) 1 is a biomarker of growing importance in the assessment of alcohol abuse after conviction for drunk driving. CDT is a more specific indicator for alcohol than traditional liver function tests and is used for identification and follow-up of chronic high alcohol consumption (1). Various methods have been introduced for assaying CDT in serum, including isoelectric focusing, ion-exchange chromatography, HPLC, capillary zone electrophoresis (CZE), and latex enhanced immunoneph-elometry (1, 2). Measuring the CDT percentage (%CDT) in a forensic context demands CZE or HPLC methodology , because it provides high-resolution separation of serum transferrin (Tf) isoforms and allows the detection of genetic variants and glycosylation disorders. In some cases, the interpretation of CDT results is hampered by the presence of mutant Tf (3). In addition to wild-type Tf (C), D variants (cathodal to C) and B variants (an-odal to C) have been described (1). The allele frequencies of the Tf subtypes vary among populations of different ethnicities (4). Exact measurement of D variants of CDT is difficult, however, because di-and trisialylated Tf may coelute with the tetrasialylated D peak in HPLC or comigrate in CZE. Algorithms have been proposed to correct for the presence of mutant Tf in capillary electropherograms (4, 5). Immunonephelometric tests in which highly specific monoclo-nal antibodies recognize the Tf gly-cosylation sites have been introduced. The N Latex CDT assay (Siemens) uses a monoclonal anti-body that recognizes Tf glycoforms lacking 1 or 2 complete N-glycans (i.e., disialo-, monosialo-, and asialo-Tf) (2). In addition, total Tf is measured. There is limited evidence for the effect of mutant Tf on CDT test results, mainly because of the small number of participants who were enrolled in the evaluation study (2). Because Tf variants are common findings (particularly in non-Caucasian populations) (3, 4), knowledge of the performance of immunonephelometric tests in the presence of Tf mutants is of practical importance. In the present study, we compared the effect of Tf variants on CZE and nephelometric CDT testing. The study was approved by the Ethics Committee of Ghent University Hospital (EC/008-2012). Within the framework of a driv-er's license–regranting program, CDT was assayed on a Sebia Capil-larys™ 2 system (3). During a 1-year period, 4878 Caucasian drivers were enrolled, and 51 drivers (1.1%) heterozygous for Tf mutants were encountered. Samples carrying heterozygous Tf were stored at Ϫ20 °C until further analysis on a BN II nephelometer (Siemens) (2). All samples were …