Clinlab Navigator


Monoclonal gammopathies constitute a group of diseases characterized by the proliferation of a single clone of plasma cells that produce a homogeneous monoclonal protein (M-protein). The most common examples include monoclonal gammopathy of unknown significance, multiple myeloma, Waldenstrom’s macroglobulinemia, and primary amyloidosis. Less common diseases include solitary plasmacytoma, POEMS syndrome,heavy-chain disease and immunoglobulin deposition disease.

Serum protein electrophoresis is the easiest means of excluding the presence of a monoclonal protein and can detect bands of 0.5 gm/dL or less. Visual examination of electrophoretic patterns by a pathologist is the most sensitive method of detecting monoclonal proteins since small bands may be obscured in densitometric scans. If a monoclonal protein is identified, its immunoglobulin class (IgG, IgA, IgM, IgD, IgE) and light chain type (kappa, lambda) are determined by immunofixation. If no monoclonal protein is detected, further testing is not warranted. An expert panel of the College of American Pathologists developed the following guidelines for the laboratory evaluation of patients suspected of having one of these conditions (Arch Pathol Lab Med. 1999; 123:106-7).

  • Serum protein electrophoresis (SPE) with high-resolution agarose gel should be the first test performed. M-protein should be quantitated by densitometry measurement of the M-protein peak.
  • If an M-protein is present, immunofixation (IFE) should be done to characterize its immunoglobulin heavy and light chain type. IFE does not need to be repeated in the future unless there is a change in a subsequent SPE pattern.
  • All cases showing monoclonal free light chains in serum should be tested for IgD and IgE paraproteins.
  • Biclonal paraproteins should be treated with 2-mercaptoethanol and retested to see if they resolve into a monoclonal.
  • Changes in level of a previously identified M-protein should be monitored by SPE and densitometric quantitation at regular intervals.
    • If asymptomatic and M-protein <1.5 g/dL, repeat annually.
    • If asymptomatic and M-protein 1.5 – 2.5 g/dL, repeat in 3 - 6 months.
    • If M-protein is >2.5 g/dL, repeat in 2-4 months.
    • During treatment, repeat every 1-2 months.
  • If M-protein is detected in serum, a 24-hour urine specimen should be submitted for electrophoresis. Urine electrophoresis is especially important for patients with hypogammaglobulinemia or monoclonal light chain in serum. The M-protein should be reported in grams per 24 hours.
  • All patients with plasma cell disorders should have direct measurement of immunoglobulins by nephelometry to determine the level of uninvolved immunoglobulins.
  • Serum viscosity should be determined when a monoclonal IgM protein level is >4 g/dL or a monoclonal IgG or IgA protein value is >6 g/dL.
  • Cryoglobulins should be assessed in all patients with an M-protein and specific complications due to cold sensitivity. Cryoglobulin assessment is particularly important for patients with monoclonal IgM proteins.


Laboratory Evaluation of Monoclonal Gammopathies

Immunofixation lab evaluation of monoclonal gammopathies


The frequency of monoclonal proteins detected at Saint Lukes hospital from 1992 – 1997 and at Mayo Medical Laboratories in 1994 is reported in the following table.


% @ SLH

% @ Mayo










Light chain






In our series, IgG lambda was the most common monoclonal protein accompanied by excess free light chains.  The most common biclonal gammopathy was IgG kappa - IgG lambda followed by IgG kappa - IgM lambda.  Biclonal gammopathies have the same clinical findings as monoclonal gammopathies. 

IgD myeloma is rare, representing <1% of all myeloma cases.  Only 60% of IgD myeloma cases have a detectable monoclonal protein in the serum at the time of presentation.  Serum protein electrophoresis may demonstrate only hypo-gammaglobulinemia. The light chain component is more commonly lambda, in contrast to the other types of myeloma which are more commonly kappa. Urine electrophoresis usually demonstrates monoclonal light chains.

In the Mayo series, patients with monoclonal proteins had the following diagnoses at the time of detection:


% of Cases















Monoclonal gammopathy of unknown significance (MGUS) is common, occurring in 1% of patients >50 years and 3% of patients >70 years. The risk of malignant transformation is 17% at 10 years after detection and 33% at 20 years.

No single laboratory test can determine whether a monoclonal protein is benign or malignant. However, benign monoclonal proteins share several characteristics.

  • The quantity of a benign monoclonal protein is usually <1.6 gm/dL
  • The concentration is stable over time
  • Normal polyclonal immunoglobulins are not suppressed.
  • Bence-Jones proteinuria is absent
  • Urine beta-2 microglobulin is <3 mg/dL.

The CV for estimating serial M-protein spikes is 8.1%. The biological variation for a serum M-protein spike within an individual is 7.8% (Clinical Chemistry 2011;57:1687-92). Following treatment, reduction in the serum M-protein spike of at least 25% is considered a minimal response while a reduction of at least 50% is considered a partial response. A complete response requires absence of a monoclonal protein by immunofixation. 

A pathologist interprets the results.

Specimen requirement is one red top or SST tube of blood or urine.

AddThis Social Bookmark Button