antibodies

Q. I have myeloma and have relapsed after a stem cell transplant.

I think I understand the disease fairly well, but I don’t get how the M spike relates to IgG, IgM, etc. and also kappa and lambda. Also – what are heavy chains and free light chains, and what does it mean if they are polyclonal or monoclonal?

A. I’m so sorry to hear about your relapse. I’ll try to shed some light on the areas you mentioned; hopefully we can clear those things up for you.

As you probably already know, in multiple myeloma, the main problem is that there are malignant plasma cells in the bone marrow. All the symptoms and complications in myeloma arise from the presence of these cells.

Normal plasma cells are a special kind of lymphocyte that makes antibodies (also called immunoglobulins or Ig, for short). Immunoglobulins have a structure that looks like a Y that has two chains: a shorter (“light”) one and a longer (“heavy”) one. You can see a bunch of Y-shaped antibodies in the image above; one of them is binding to a cell. There are five different kinds of heavy chains (gamma, mu, epsilon, delta, alpha) and two different kinds of light chains (kappa and lambda). The heavy chains are abbreviated G, M, E, D, and A. To make an immunoglobulin molecule, you pick one heavy chaina and one light chain – so there a bunch of different combinations: IgG kappa, IgG lambda, IgM kappa, etc.

Normal immunoglobulins are all slightly different. First, you have all the different types (IgG kappa, etc.). Then, even within those types, there is a huge amount of variability, because of the huge amount of bad stuff, like viruses, that we encounter in the environment. We need to have antibodies against all these different things!

In myeloma, the plasma cells are what we call monoclonal. That means they all descended from an initial cell, which divided into two, and then those two divided into four, and so on. So all the cells in this malignant population of plasma cells are exactly the same (monoclonal), and they all make the exact same kind of immunoglobulin (IgG kappa, say), which we can measure in the blood. Normal plasma cells, in contrast, are called polyclonal, because they are all different from each other.

You can use the words monoclonal and polyclonal to describe immunoglobulins too. Monoclonal immunoglobulins are all exactly the same and are made by a population of monoclonal plasma cells. Polyclonal immunoglobulins are all slightly different from each other, and are made by normal, polyclonal plasma cells.

It’s this big group of monoclonal immunoglobulins, made by the monoclonal, malignant plasma cells, that we refer to as the M-spike (some sources say the M stands for monoclonal). An M spike can be IgG kappa, or IgA lambda, or any possible combination of heavy and light chains. Sometimes, the malignant plasma cells make just heavy chains or just light chains (these are called “free light chains”). The cells are malignant, so they can do whatever they want – they don’t have to make correctly-formed immunoglobulins if they don’t feel like it. So sometimes the M spike will consist of just gamma chains, or just kappa chains, for example.

As part of your initial workup, the lab will find out what type of M-spike you have – and then this M-spike will be followed throughout the course of your disease. When it goes down, it’s assumed that there are less malignant plasma cells around. When it goes up, that means there are more malignant plasma cells. Myeloma treatment has improved drastically in the last several years – and I hope your M spike goes way down! In fact, I hope you never see it again.