What are the tests for monoclonal gammopathy (and when would you test)?

What would the lab findings of monoclonal gammopathy be? (And why should I care?) 

ALL proteins in the blood can be divided into 4 categories:

Screen Shot 2016-12-03 at 3.03.30 PM.png
Albumin, alpha, beta, and gamma. aafp.org

Monoclonal gammopathy is a fancy way of saying, “a disease in which there is a disproportionate amount of a single kind of gamma protein being produced.”It may also be called paraproteinemia or plasma cell dyscrasia (ugh, so many syllables). It manifests as a spike in the gamma category on the far right. An elevated serum protein level, especially if the albumin is low/normal, can be a clue. The next step is to get a serum protein electrophoresis (SPEP) to prove that there is a gamma spike, or excess of gamma.

Monoclonal gammopathies of this”gamma” category (aka, “immunoglobulins” which includes antibodies) includes MGUS, multiple myeloma, amyloidosis, and some lymphomas and leukemias. The confusing part is that, philosophically, myeloma can be considered a type of lymphoma and MGUS and myeloma may eventually become a leukemia or lymphoma (which also can become a leukemia eventually). It’s a big conceptual mess–but obviously, these are important diseases.

How do you further differentiate the monoclonal gammopathies?

  • Can you identify the abnormal protein? (We will get into this below)
  • What does the blood smear show? (Is there evidence of blasts in the periphery, or dysplastic cells?)
  • What does the bone marrow biopsy show? (This can help distinguish MGUS and multiple myeloma, for instance)
  • Are there clinical signs/symptoms?

How do you identify the abnormal protein, and how does that correlate clinically? 

Now that you know you’re dealing with a monoclonal gammopathy, what do you do? First, what kind of Ig predominance does the gammopathy have? (For instance, if there is an IgM spike, this is Waldenstrom’s macroglobulinemia, or sometimes myeloma, but if there is an IgA or IgG spike, MGUS or myeloma are more likely.) Get serum immunofixation.

Screen Shot 2016-12-03 at 3.05.53 PM.png


Next, are there free light chains?

They’re “free” because they’re free floating! Get it? Slideshare

The reason a separate free light chain assay is needed is because in about 15% of myelomas, there is no heavy chain, just a light chain. This is also why we order a urine protein electrophoresis (UPEP)–it’s much more sensitive for light chains than SPEP. The presence of an abnormal light chain ratio usually indicates myeloma or amyloidosis.

Sometimes, if you have a patient with a new acute kidney injury, you will be asked to get SPEP, UPEP, and serum FLC to “rule out myeloma kidney.” The utility of these tests is not totally clear to me, so I’m not going to speculate as to how strong of an indication it is.



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