Monoclonal gammopathy

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). 

Guidelines for clinical and laboratory evaluation of patients with monoclonal gammopathies have been proposed (K7). These proposals address in addition electrophoretic, immunofixation, and quantitative techniques for measurement of M protein, and also provide guidelines for serum viscosity and cryoglobulin measurements. 

Patients with monoclonal gammopathy of undetermined significance, the so-called benign or more correctly essential monoclonal gammopathy, generally... 

The distinction between essential monoclonal gammopathy and asymptomatic multiple myeloma can be difficult in subjects whose M protein and Bence-Jones protein ranges and percentage of plasma cells in bone marrow overlap. 

Patients without coexisting multiple myeloma or WM secrete small amounts of M protein (< 10 g/L) and their bone marrow is infiltrated with a lesser percentage of atypical plasma cells similar to that seen in essential monoclonal gammopathy (<10%). 

E2. Ely, S. A., and Knowles, D. M., Expression of CD56/neural cell adhesion molecule correlates with the presence of lytic bone lesions in multiple myeloma and distinguishes myeloma from monoclonal gammopathy of undetermined significance and lymphomas with plasmacytoid differentiation. Am. J. Pathol. 160, 1293—1299 (2002). 

K35. Kyle, R. A., Monoclonal gammopathy of undetermined significance and solitary plasmacytoma. Implications for progression to overt multiple myeloma. Hematol. Oncol. Clin. North Am. 11,... 

L8. Lima, M., Teixeira Mdos, A., Fonseca, S., Goncalves, C., Guerra, M., Queiros, M. L., Santos, A. H., Coutinho, A., Pinho, L., Marques, L., Cunha, M., Ribeiro, P., Xavier, L., Vieira, H., Pinto, R, and Justica, B., Immunophenotypic aberrations, DNA content, and cell cycle analysis of plasma cells in patients with myeloma and monoclonal gammopathies. Blood Cells Mol. Dis. 26, 634-645 (2000). 

Peripheral neuropathy occurs in about 16% of patients with MGUS, being particularly common in those with an IgM monoclonal gammopathy [128], The IgM fraction of such patients includes antibodies to myelin-associated glycoprotein (MAG antibodies) that bind to determinants in peripheral nerve myelin, and, as shown by animal models, the antibodies mediate the myelin injury and secondary nerve damage [129]. The patients usually have a distal symmetric neuropathy, usually with predominant sensory affection, and the neurological symptoms frequently precede the detection of gammopathy [130]. 

Nobile-Orazio E, Barbieri S, Baldini L, Marmiroli P, Carpo M, Premoselli S, et al. Peripheral neuropathy in monoclonal gammopathy of undetermined significance Prevalence and immunopathogenetic studies. Acta Neurol Scand 1992 85(6) 383—390. 

Rl. Radi, J., Age-related monoclonal gammopathies Clinical lessons from the aging C57BL mouse. Immunol. Today 11, 234-236 (1990). 

Chassande B, Leger JM, Younes-Chennoufi AB, Bengoufa D, Maisonobe T, Bouche P, Baumann N (1998) Peripheral neuropathy associated with IgM monoclonal gammopathy correlations between M-protein antibody activity and cUnical/electrophysiological features in 40 cases. Muscle Nerve 21 55-62... 

Pasqualetti P, Collacciani A, Casale R. 1996. Risk of monoclonal gammopathy of undetermined significance A case-referent study. Am J Hematol 52 217-220. 

A 76-year-old man, who had taken amiodarone for an nnspecified time, developed a monoclonal gammopathy with bone marrow grannlomata (168). After another 2 years he developed hepatic grannlomata and the amiodarone was withdrawn. The bone marrow grannlomata resolved within a few months. Infections were exclnded and there was no evidence of sarcoidosis. 

The safety of growth factors in patients with myeloma is also of concern, as they can stimulate the proliferation of myeloma cells through IL-6 expression. Only isolated case reports, including accounts of the mobilization of clonal myeloma cells into the peripheral circulation, rapid progression of a multiple myeloma, or the new onset of a monoclonal gammopathy, directly or indirectly support the view that caution should be exercised in patients with multiple myeloma (SED-13,1118) (92). 

Blood from patients with monoclonal gammopathies cannot be measured the values will be too high. 

The converse of these criteria suggests that the condition is benign or monoclonal gammopathy of unknown significance (MGUS). Even then, patients should be monitored for at least 5 years. 

In monoclonal gammopathies, the IFE patterns usually yield a distinct, sharply defined precipitin band with one heavy-chain and one light-chain antiserum. These bands match the location of the particular immunoglobulin in the reference pattern (Figure 20-10). A second, fainter band of free light chains may also be present. 

A comparison of IFE and lEP for two patients with monoclonal gammopathies is shown in Figure 20-10. The principles of lEP are described in Chapters 5 and 9. 

Figure 20-10 Comparison of immunofixation electrophoresis (IFE) and immunoelectrophoresis (lEP) for two patients with monoclonal gammopathies. A, Patient specimen with an IgG (kappa, k) monoclonal protein as identified by IFE.The arrow indicates the position of monoclonal protein.After electrophoresis, each track except SPE is reacted with its respective antiserum, then all tracks are stained to visualize the respective protein bands. (SPE Chemically fixed serum protein electrophoresis IgG, IgA, IgM, k, and A, indicate antiserum used on each track.) B, Same specimen as in A, with proteins identified by lERThe arrow indicates the position of monoclonal protein. Norma control (C) and patient sera (S) are alternated. After electrophoresis, antiserum is added to each trough as indicated by the labels ig (polyvalent Ig antiserum), IgG, IgA, IgM, K, and A The antisera react with separated proteins in the specimens to form precipitates in the shape of arcs.The IgG and k arcs are shorter and thicker than those in the normal control, showing the presence of the IgG (k) monoclonal protein.The concentrations of IgA, IgM, and A,-iight chains are also reduced. C, Patient specimen with an IgA (lambda, A,) monoclonal protein identified by IFE procedure as described in A. D, Same specimen as in C with proteins identified by lEP as described in B.The abnormal IgA and A,-arcs for the patient specimen indicate an elevated concentration of a monoclonal IgA (A.) protein. Ait separations were performed using the Beckman-Coulter Paragon system.

Monoclonal gammopathy Presence of narrow protein band in the fi-y region may indicate the... 

Serum immunofixation electrophoresis of two patients with monoclonal gammopathies. Pattern A represents IgG(/c) monoclonal gammopathy and pattern B represents IgA(/r) monoclonal gammopathy, as indicated by arrows. The procedure consists of serum protein electrophoresis (SPE) separation, reaction of each track with the exception of SPE with specific respective antiserum, followed by protein staining to make visible the respective bands. 

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