Extreme elevation of transcobalamin II levels in multiple myeloma and other disorders

The source of transcobalamin (TC) II in man and the factors controlling its serum level are unknown. We studied 98 patients with extreme elevation of this protein (>2000 ng/liter, a level approximately twice normal mean), grouped by predominant diagnosis in the categories of liver disease (primarily alcoholic cirrhosis) (17 patients), infection and other inflammatory disorders (21), cancer (17), lymphoproliferative disorders (9), and, most interestingly, multiple myeloma and related disorders (25); the remaining patients had miscellaneous disorders. Although many patients had persistent TC II elevation, in seven instances transitions between high and normal TC II levels were identified. These transitions most often appeared to parallel changes in acute inflammatory processes. Thus TC II had many of the characteristics of an acute-phase reactant. Of the possible cellular sources for TC II previously suggested, a myeloid origin was not supported by our data, and other evidence may be marshalled against a reticuloendothelial source; a hepatic source remains possible. However, our striking finding of TC II elevation in multiple myeloma and Waldenstrom macroglobulinemia and the frequent coexistence of hyperglobulinemia in the other patients suggests that plasma cells and B lymphocytes also merit consideration as sources.