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ABNORMAL HETEROGENEITY OF SERUM TRANSFERRIN—A NEW DIAGNOSTIC MARKER OF ALCOHOLISM?

A number of chemical abnormalities may be found in association with excessive alcohol consumption. Some of these are often encountered clinically and may be used as markers for the detection of alcoholism, for example peripheral macrocytosis, elevated values of serum iron, serum alpha-lipoproteins, and muscle and liver enzymes especially gamma-glutamyltransferase (Sullivan & Herbert 1964, Johansson & Laurel1 1969, Rosalki & Rau 1972). These tests are, however, not always satisfactory mainly because of their lack of specificity. From a clinical point of view it is clear that the search for more specific tests is still strongly needed. Since some years we have been interested in studying protein heterogeneity mainly in cerebrospinal fluid by means of isoelectric focusing. During this work we made some observations on the serum transferrin pattern in alcoholic patients which inspired us to the investigation I shall present today (Stibler & Kjellin 1976, Stibler et al. 1978, 1979). To you who might not be familiar with isoelectric focusing I shall briefly explain the principle of this method (Vesterberg & Svensson 1966). It is based on the fact that since for example proteins are charged molecules they may be separated according to their net charges. This is accomplished by way of a pH gradient which is created by means of ampholytes covering the desired pH range and an electrical field. Depending on the charge of the molecule to be separated it will move a certain distance along the pH gradient until it becomes uncharged, that is until it has reached its isoelectric point. At that point the protein will become concentrated and focused into a very narrow and sharp band. Because only an extremely small charge difference is needed to separate different molecules one can see that most proteins are microheterogeneous and consist of several molecular populations with differences in their net charges, and one could therefore talk about isoproteins just like isoenzymes. This phenomenon is what we have studied in transferrin in alcoholics.