Case 390 -- A man in his 70's who has monoclonal gammopathy of undetermined significance, or does he?


The position of the band and the observation of material in the serum raised the possibility that fibrinogen was the band in the gamma region on serum protein electrophoresis. Polyclonal antibody to fibrinogen was available in the laboratory, and immunofixation electrophoresis using anti-fibrinogen was performed (Figure 3).

Fibrinogen is not normally seen in serum but if present would appear in serum electrophoresis as a distinct band between the β- and γ-globulins. A fibrinogen band can be distinguished by examining the specimen for a fine clot and by repeat electrophoresis of a thoroughly clotted sample. Confirming the origin of the band as fibrinogen can also be done using the polyclonal antibody to fibrinogen. Because of its position, a fibrinogen band can, as in this case, mimic a monoclonal spike seen in monoclonal gammopathy of undetermined significance or multiple myeloma.

Chronic inflammatory demyelinating polyneuropathy affects mostly adults, males greater than females. Symptoms are both motor and sensory in most cases and include weakness of limbs (usually symmetric). Approximately 25% of patients also have monoclonal gammopathy of undetermined significance (MGUS).

No absolute definition exists for MGUS. Features include:

The major reason for concern in the patient with MGUS is the progression to a monoclonal disease such as multiple myeloma, primary amyloidosis, or other B-cell proliferative disorder. A Mayo Clinic series of 1,384 patients showed a rate of progression of approximately 1% per year.

Predictors of progression (in terms of relative risk) are:

Patients with CIDP-MGUS may have less severe weakness, greater imbalance, leg ataxia, vibration loss in the hands, and absent median and ulnar sensory potentials, but are just as likely as other CIDP patients to respond to standard therapy with plasma exchange. The monoclonal immunoglobulin can be IgG, IgM, or IgA. Patients with IgM tend to have more sensory findings, a more protracted course, and a less favorable response to therapy. Anti-myelin-associated glycoprotein antibodies and antiganglioside antibodies have been found in patients with CIDP with MGUS, most frequently with IgM monoclonal immunoglobulin. Controversy exists regarding the pathogenesis of the polyneuropathy when MGUS accompanies the disease - activation of immune response versus destabilization of myelin metabolism.

In this case, using monoclonal antibody specific for fibrinogen, we were able to confirm that this patient did not have monoclonal protein in his serum. If the immunofixation had not been performed and only protein electrophoresis reported, it is possible that this patient would have been evaluated for a monoclonal protein that did not exist. This emphasizes the importance of appropriate characterization when a monoclonal protein is detected by serum protein electrophoresis.


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Contributed by Beth Clark, MD, Bruce Rabin, MD, PhD

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