Abnormal Nucleic Acid Metabolism of Lymphocytes in Plasma Cell Myeloma and Macroglobulinemia

Twenty-six patients with multiple myeloma and macroglobulinemia of Waldenström were studied clinically and immunologically with characterization of their paraproteins and normal immunoglobulins, as well as by in vitro culture of their peripheral lymphocytes for evaluation of DNA and RNA synthesis after phytohemagglutinin stimulation. The lymphocytes of the patients were found to be significantly deficient in response to PHA as compared to normals and patients with benign hypergammaglobulinemia. Levels of normal immunoglobulins were reduced in almost all of the paraproteinemic patients, but there was not a direct correlation between lymphocyte unresponsiveness and immunoglobulin deficiency. The defect in lymphocyte function appeared to be cellular inasmuch as normal lymphocytes had normal DNA synthesis when cultured in myeloma plasma. The decrease in lymphocyte nucleic acid synthesis appeared to be unrelated to immunoglobulin class, quantitative levels or antigenic characteristics of the patients’ paraproteins. Untreated myeloma patients with a past history of infection had lower levels of lymphocyte DNA synthesis than those patients who lacked such a history, suggesting a relationship between the in vitro lymphocyte response to PHA and the in vivo response to the antigenic challenge of bacterial infection.