Interference of transferrin isoform types with carbohydrate-deficient transferrin quantification in the identification of alcohol abuse

Background: Isoforms of transferrin interfere with measurement of carbohydr ate-deficient transferrin (CDT) as a marker of heavy alcohol consumption. W e 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 wi th a congenital disorder of glycosylation (CDG Ia) and from 6 healthy carri ers of CDG Ia. The CDTect, %CDT-TIA, and new %CDT immunoassays were compare d with HPLC (%CDT-HPLC), Transferrin isoform pattern were evaluated by isoe lectric focusing (IEF). Results: Transferrin BC and CD heterozygotes were found at frequencies of s imilar to0.7% and similar to0.2%, respectively. Another transferrin C subty pe, where di- and trisialotransferrin partly coeluted (tentatively identifi ed as C2C3), was observed in similar to0.6%. Compared with the %CDT-HPLC me thod, the immunoassays often produced low results for transferrin BC and hi gh results for transferrin CD and "C2C3". A very high trisialotransferrin v alue (frequency similar to1%) often produced high CDT immunoassay results. In four of six healthy carriers of CDG Ia, a- and disialotransferrin were h ighly increased and the HPLC and IEF isoform patterns were indistinguishabl e from those in alcohol abuse. Conclusions: Rare transferrin isoform types and abnormal amounts of trisial otransferrin (total frequency similar to2-3%) may cause incorrect determina tion of CDT with immunoassays, The observed variants were readily identifie d by HPLC and IEF, which can be recommended for verification of CDT immunoa ssay results in doubtful cases. In healthy carriers of CDC Ia, CDT is high by all assays. (C) 2001 American Association for Clinical Chemistry.