Macroglobulinemia

As early as 1958 Bergot et al. (B5) first described the association between secondary macroglobulinemia in Africa and trypanosomiasis. This was confirmed by Dreyfus et al. in 1960 (D4) and later by Mattern et al. (M33), who adopted the immunoelectrophoretic technique to indicate the high IgM content in the sera of affected persons. In 1963, Charmot et al. observed (C12) that the principal cause of macroglobulinemia in Africans is trypanosomiasis. 

In Waldenstrom macroglobulinemia the serum IgM value is invariably above 1000 mg/100 ml, and the serum should be diluted before any attempt is made to quantitate the IgM protein by immunochemical testing since antigen excess may obscure the precipitin ring and give falsely low results. 

I.I. Immunoelectrophoresis. In Waldenstrom macroglobulinemia the IgM precipitin line invariably has a pronounced double curvature, and when compared with a normal control serum the IgM pattern of the former is much more distinct. After washing the agar gel with saline for 2 to 3 days, there usually still remains a massive amount of protein (IgM) spontaneously precipitated around the point of application. This feature is also characteristic of cryoglobulinemia—frequently seen in populations who live in areas where parasite diseases are common. 

Sephadex Gel Filtration. The most common type used is the Sephadex G-200. The emergence soon after the void volume of a massive peak which is more prominent than the other peaks is compatible with a diagnosis of Waldenstrom macroglobulinemia. The test is a very useful aid in the diagnosis of Waldenstrom macroglobulinemia. 

Ultracentrijugation. In those laboratories where an ultracentrifuge is available, the pattern obtained of the serum of a patient with Waldenstrom macroglobulinemia is very characteristic. Frequently more than 30% of the total serum proteins could be accounted for by the 19 S peak. Bence Jones protein is not an uncommon finding in patients with Waldenstrom macroglobulinemia and was detected in patients both in Nigeria and Jamacia with the disease. 

Viscosity of the Serum. Provided the apparatus is available, this is a rather simple test to perform and the information obtained helps to establish the condition. Using an Ostwald viscometer at 20.0°C and 37.5°C in thermostatically controlled water baths, it was found that patients with macroglobulinemia had scrum with relative viscosity of 2.40-15.80. The normal is 1.54r-1.80. 

Malignancies of various types— multiple myelomatosis, Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, reticulum cell sarcoma, Hodgkin s disease, Burkitt s lymphoma and other malignancies of the reticuloendothelial system... 

Chlorambucil is used primarily as daily palliative therapy for chronic lymphocytic leukemia, Walden-stroom s macroglobulinemia, myeloma, and other lymphomas. 

This chapter reviews our current understanding of the mechanism of action of monoclonal antibody (especially rituximab), as well as the role of Fey receptor and Fey receptor gene polymorphisms, and their impact on treatment outcomes in hematologic malignancies including follicular lymphoma (FL), diffuse large B-cell lymphoma (DL-BCL), Waldenstrom s macroglobulinemia (WM), and chronic lymphocytic leukemia (CLL). 

Waldenstrom s macroglobulinemia (WM) is an uncommon lymphoid malignancy characterized by IgM monoclonal gammopathy and intertrabecular marrow infiltration by small lymphocytes expressing CD20 antigen. Currently, rituximab can be used for the treatment of WM with response rates between 20% and 50% (62,63). 

Johnson SA. Advances in the treatment of Waldenstrom s macroglobulinemia. Expert Rev Anticancer Ther 2006 6 329-334. 

Treon SP, Hansen M, Branagan AR et al. Polymorphisms in FcgammaRIIIA (CD16) receptor expression are associated with clinical response to rituximab in Waldenstrom s macroglobulinemia. J Clin Onco/2005 23 474 81. 

Pemis, B., Brouet, J.C., Seligmann, M. (1974). IgD and IgM on the membrane of lymphoid cells in macroglobulinemia. Evidence for identity of membrane IgD and IgM antibody activity in a case with anti-IgG receptors. Eur. J. Immunol. 4,776-778. 

H12. Harisdangkul, V., McDougal, J. S., and Christina, C. L., Naturally occurring low molecular weight IgM in patients with rheumatoid arthritis, systemic lupus erythematosus, and macroglobulinemia. I. Purification and immunologic studies. J. Immunol. 115, 216-... 

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