What is a monoclonal protein? Why does it occur? How is it detected?

So in the blood, we can detect this protein by some chemical properties.

Basically, not to go into too much sort of wet chemistry, but we essentially run all of the blood proteins across an electrical gradient and they separate based on how they travel through that gradient.

And you can detect a normal pattern, something called a polyclonal pattern on this thing called an electrophoresis, or you can detect a spike. That’s actually a question I get asked in the clinic almost all the time.

This is a protein that we can detect in the blood, but it really derives from something called an antibody. Myeloma, at its core, is a cancer of plasma cells. Plasma cells are the body's natural factory for antibodies.

If someone early in their childhood, for example, receives a vaccine to chicken pox or measles, or let's say they actually had chicken pox or measles, they will then go on to develop an immune response, one aspect of which is the development of a clonal memory or population of plasma cells.

What that means is you have a small population of plasma cells in your body that make a specific antibody that targets, let's say, the chicken pox or the measles and helps protect you from subsequent infections because you have some amount of that antibody in your blood.

In a healthy person, the body usually makes many clones of many different plasma cells, which each make their own antibodies. These antibodies fight off many different diseases. This is polyclonal because there are many clones of many distinct plasma cells.

Myeloma is a cancer of plasma cells, and since it is derived from plasma cells, it also makes an antibody. The myeloma is a clonal proliferation, meaning it's a proliferation or multiplication of the same cell or a cell derived from the same plasma cell.

And it therefore makes the same kind of antibody over and over again. We detect this as a clonal spike in the blood when we run something called an aspect on the blood.

Too much of a specific clonal protein derived from these clonal plasma cells.

And a bone marrow biopsy. What you're really looking for is how the cells actually look.

You can't really detect the monoclonal protein or the M-spike. What you do detect is the type of antibody. So these antibodies can come in several flavors, and the flavors each have like a chocolate and vanilla.

So what I mean by that is you can have an IgA antibody, an IgG antibody, IgE, IgD, IgM. But in our case, we call them kappa and lambda.

And if you have a polyclonal response, there's an expected ratio of kappa and lambda that can be detected or essentially stained for in the bone marrow and visualized. If you have a clonal proliferation or multiplication of plasma cells, then they tend to be all kappa or all lambda, or that normal ratio is significantly skewed toward one or the other.

And that tells you that you have a clonal process. One can look at this in a variety of different ways in the bone marrow. You can do that on a biopsy and you can also do that on the aspirate as well, using something called flow cytometry.