WALDENSTROMS MACROGLOBULINEMIA WITH AN IGM PARAPROTEIN THAT IS BOTH ACOLD AGGLUTININ AND A CRYOGLOBULIN AND HAS A SUPPRESSIVE EFFECT ON PROGENITOR-CELL GROWTH

Background: A patient with Waldenstrom's macroglobulinemia was admitte d to the hospital with fever, leg pain, and dyspnea. The patient had g as gangrene of the left leg that required above-the-knee amputation. P lasmapheresis was instituted to treat hyperviscosity. Study Design and Methods: The patient's serum contained an IgM-kappa paraprotein, a cr yoglobulin, and a cold agglutinln. The serum was studied. Results: The patient's red cells typed as A(1), Rh-positive. The direct antiglobul in test was negative. The serum contained a cold agglutinin with anti- Pr cold agglutinin specificity (titer 4096). Maximal thermal range was 30 degrees C. Following dithiothreitol treatment, the cold agglutinin activity disappeared. The serum IgM concentration in the tested sampl e was 62.3 g per L. The cold agglutinin titer in the supernatant after removal of the cryoglobulin was 256, and the IgM level was 0.31 g per L. Redissolving the cryoglobulin in a equivalent volume of saline res ulted in a cold agglutinin titer of 4096 and an IgM level of 68.4 g pe r L. These results indicate that the cryoglobulin and the cold aggluti nin are the same paraprotein. Serum protein electrophoresis using agar ose gel and immunofixation of the serum revealed an IgM-kappa monoclon al band. Progenitor cell assays were performed by adding the patient's serum at final concentrations of 0, 1, 5 and 10 percent (vol/vol) to patient's and normal donor's peripheral blood mononuclear cells. Inhib ition of burst-forming units-erythroid and colony-forming units-granul ocyte/macrophage by the patient's serum was demonstrated. Appropriate controls and the use of the serum of another patient with Waldenstrom' s macroglobulinemia did not suppress progenitor cell growth. The patie nt's serum inhibited colony formation in a dose-response fashion. Conc lusion: Reports of cryoprecipitable cold agglutinins are rare. This ca se is unusual because the IgM-kappa paraprotein was also a cold agglut inin with anti-Pr specificity and erythroid and granulocyte-macrophage progenitor cell-suppressive properties.