Q.Â I have multiple myeloma, and I read your postÂ What is an M-spike, and it wasÂ excellent contribution which I have been looking for in months.Â Please, can you tell me how the M-spike is quantifed?
A.Â That’s a great question! As you alluded to, there are a couple ways of looking at a monoclonal antibody: identification (i.e., is it IgG kappa, or IgA lamda, or something else) and quantification (how much of it is present). Both pieces of information are useful in diagnosing and following multiple myeloma.
Is a monoclonal protein present?
The first thing that’s usually done in the lab is serum protein electophoresis (SPEP). This procedure tells you whether there is a monoclonal protein present. You also do this procedure using urine, because sometimes myeloma cells will only make light chains, which end up being peed out in the urine (so if you only did a SPEP, you would miss them). In an SPEP, the proteins in the serum are separated by regular old electrophoresis, using a gel. The gel is stained with a dye, and the percent of protein in the various fractions is is determined.
You can see an example above, with normal serum proteins in green, and proteins from a patient with myeloma in red. Albumin, as you can see, is the most abundant protein in blood, and it has its own region way on the left. Immunoglobulins usually migrate to the gamma region; you can see a small, broad bump in the normal serum (corresponding to the polyclonal immunoglobulins in blood, all of which migrate to a slightly different place on the gel) and a big spike in the blood from the patient with myeloma (corresponding to the monoclonal immunoglobulin, all of which migrates to the same exact spot on the gel).
What kind of immunoglobulin is it?
If you find a monoclonal immunoglobulin on an SPEP (or UPEP), you can characterize it using immunoelectrophoresis or immunofixation. These tests tell you the nature of the immunoglobulin heavy and/or light chains (does the monoclonal immunoglobulin consist of IgA heavy chains and kappa light chains, for example, or is it just IgG?).
How much of it is present?
To quantify immunoglobulins, you can do one of two things:
- Determine the total serum protein concentration using a separate assay, and then use that number to convert the protein percentages (from the SPEP) to actual concentrations.
- Use something called immunonephelometry (NEPH), which uses light scatter generated by the binding of heavy chain-specific antisera, to determine how much immunoglobulin is present.
Without getting into too much detail, there are differences in accuracy in these two tests, and depending on what kind of monoclonal antibody you have, and how much you have, one or the other test may perform better. Whichever test is used, it’s probably best to just pick one and stick to it when monitoring a patient; if you alternate between the two methods, you might not get consistent results.