The Association of Gaucher’s Disease and Dysproteinemias

Y. Shoenfeld, MD, Department of Medicine ‘D’, Beilison Medical Center, Petah Tikva (Israel) The first communication of the existence of polyclonal (diffuse) hypergammaglo-bulinemia in Gaucher’s disease was reported by Goldjarb et al. [4] in 1950 in a group of patients under the age of 30 years. 13 years later, the first report of a patient with Gaucher’s disease and monoclonal gammo-pathy was published [8], followed by another report [17]. Later on, the coexistence of multiple myeloma and Gaucher’s disease was described [2, 13]. Pratt et al. [15] described 16 patients with Gaucher’s disease of whom 6 had diffuse hypergammaglo-bulinemia and four monoclonal proteins, all of them of the IgG type with ‘K’ light chains with a concentration of the monoclonal protein of between 2,500 and 3,600 mg/dl. Except for 1 patient, none had decreased concentrations of the polyclonal protein. The monoclonal proteins tend to appear in splenomegalic patients with Gaucher’s disease above the age of 50 [15], while they are not prevalent in splenectomized patients, a fact that may be associated with the participation of the spleen in the production of these proteins. Pratt et al. [15] suggested that patients with Gaucher’s disease have continuous an-tigenic stimulation which brings about the development of diffuse hyperglobulinemia and later on, in elderly patients, the appearance of monoclonal proteins and even multiple myeloma [19]. Despite the small number of cases reported concerning the coexistence of multiple myeloma and Gaucher’s disease, an association exists between multiple myeloma and diseases caused by other distorted lipid metabolism [1, 14, 18]. Possibly, these lip-ids may be the antigen which induces the immunoglobulin synthesis. In effect, the repeated intraperitoneal injection of fat in BALB/c mice brought about increased production of gammaglobulins and eventually the appearance of overt multiple myeloma [9, 14]. In Gaucher’s disease, there are at least three substances which may possibly serve as antigens: (1) Glucocerebroside, a lipid which accumulates in the reticuloendothelial system. (2) Glucocerebrosidase, which in patients with Gaucher’s disease has a decreased activity in spite of its relatively high levels [10]. Moreover, in patients with Gaucher’s disease this enzyme differs quantitatively [7] as well as structurally [10] from the enzyme present in healthy subjects. (3)