Monoclonal hypergammaglobulinemia monoclonal gammopathy

Recognition of monoclonal gammopathy

Monoclonal gammopathy is recognized when the physician notes a monoclonal peak on the serum protein electrophoresis. Immunoelectrophoresis and immunofixation to identify the type of monoclonal peak reveals an IgG, IgA, IgM or rarely an IgD or IgF. monoclonal protein with either k or \ light chains. Urine electrophoresis may reveal free monoclonal light chain.

Pathophysiology of monoclonal gammopathy

In contrast to polyclonal processes where IL-6 acts as a B cell differentiating factor, in monoclonal gammopathy and myeloma IL-6 is important for myeloma cell growth. Increased serum levels of IL-6 may be found in myeloma. Serum levels of C-reactive protein, which is synthesized by the liver in response to IL-6, are also elevated. Evidence has been presented for both autocrine and paracrine IL-6-induced growth of myeloma cells. IL-6 levels arc elevated in the serum of patients with active, high tumor burden disease. Soluble receptor for IL-6 acts as a cytokine agonist, enhancing the response to IL-6. Other interleukins such as IL-3 probably also play a role in sustaining myeloma cell growth. IL-6 also inhibits glucocorticoid and Fas-induced apoptosis, further contributing to myeloma cell growth.

Myeloma cells grow selectively in the marrow. Compared to B cells, myeloma cells have lost surface CD45 and CD19, and gain CD.38. Normal plasma cells do not lose CD19. Myeloma cells probably home to the marrow using surface adhesion molecules which can trigger stromal cells in the marrow to release IL-6. CD56, a neural cell adhesion molecule (NCAM) not present on normal plasma cells but present on the surface of most myeloma cells, probably aids in this process. Myeloma cells produce IL-ip which may increase the expression of surface adhesion molecules and induce stromal cells, osteoblasts and osteoclasts to produce IL-6.

Cytokines produced by myeloma cells such as IL-1(3 or tumor necrosis factor a (TNFa) arc osteoclast activating factors which can cause bone damage.

Table 2 Most common causes of monoclonal gammopathy

Malignant

Premalignant

Other

Multiple myeloma

Monoclonal

Amyloidosis

(MM)

gammopathy of

Heavy chain

Solitary

undetermined

diseases

plasmacytoma

significance

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