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 chain 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.
This is the most simple, easy to read and well explained text about MM that I’ve read so far. Congrats.
Sometimes, these light-chains can appear in urine and are suggestive of Multiple Myeloma or Waldenström’s Macroglobulinemia. And there’s a fancy name to it: Bence-Jones Proteinuria
^^
Absolutely right on the Bence-Jones proteins! Sometimes, you only see those (and no heavy chains or complete immunoglobulins) – and they just get peed out in the urine. Which is why it’s important to do not just a serum protein electrophoresis but a urine protein electrophoresis.
My husband has AL Amyloidosis.
You indeed have a gift of making the complicated easy to understand. My husband was recently diagnosed with AL amyloidosis with both cardiac and kidney involvement. They call his disease biclonal gammopathy though originally we were told he had MGUS back in May 2012. He does not have multiple myeloma. He recently started chemo. What blood tests will we be following going forward? We are hoping for remission with this CYBOR-D therapy. They indicated this course of treatment would be followed by a stem cell transplant.
Hi Carole – So sorry to hear about your husband’s disease. The newer drugs for plasma cell malignancies are so much better than they were even a few years ago – I hope he does really well. The main blood test of interest will likely be the M spike. That’s a fairly good indicator of how many plasma cells there are (and therefore how his disease is doing). The doctor will also most likely follow his hemoglobin, white count and platelet count (those are indicators of how well his marrow is working) and probably a creatinine (to monitor his kidney function). Bone marrow biopsies will probably be done at some point too. Best wishes Carole!
hi Kristine,
i’m about to give a presentation on MM, and you have explained this so well…thanks so much
cheers
Mandy
So glad it helped!
Kristine, My husband was diagnosed with Kappa Light Chain Deposition Disease and had a stem cell transplant in May, 2011 which didn’t do what it was supposed to so he had chemotherapy from August till November of the same year. The disease has been stable until now when his numbers have gone up and he will start chemo again this week, after the Dr. gets the results of the bone marrow biopsy from last week. I don’t know if you needed all this info for my question which is this:Is kappa MM the same as what he has? As you probably know, the Dr.s say it’s not MM but they are treating it the same, and sometimes they call it myeloma, but still say it’s not exactly a cancer. Can you please explain to me the difference? I appreciate your help in clarifying this for us.
Dear Eda,
I’m so sorry to hear of your husband’s disease. Light chain deposition disease is a rare disorder (as you probably have learned by now). It is not the same thing as myeloma, though many patients with light chain deposition disease also have myeloma.
The main thing that happens in LCD is that light chains (fragments of antibodies) are deposited in various tissues throughout the body. Most patients have kidney involvement, but other organs are aslo commonly affected.
Many patients (about half) have some sort of white blood cell cancer – often myeloma, but sometimes lymphoma or other diseases. Some patients don’t seem to have any sort of underlying cancer.
There isn’t a single standard treatment for the disease (probably because it is so rare). If there is an underlying cancer (like myeloma), the chemotherapy drugs used would probably be similar to those used in that particular cancer.
So in short: LCD is different than myeloma, but many patients also have myeloma. Your doctor should be able to tell you whether your husband also has myeloma or not (they would determine that by looking at your husband’s bone marrow).
I wish you the best – I hope you can find a doctor that will take the time to sit down with you and answer all your questions.
Very nice explanation..
Husband has multiple myeloma since 1998-2 stem cell tansplants and a wide variety of chemo drugs. We have found a combination chemo drugs that appear to be working. Why do they not explain things in simple lay language that I can understand what is going on? They make it so confusing- ie immunotyping electrophersis demonstrates the presence of an IgG kappa monoclonal gammopathy and Bence Jones protein is not detected. We have a doctors appointment in 1 week but, ???
I’m so sorry! You’ve been through a long haul together.
I don’t know why some doctors can’t or won’t explain things in normal human language. It’s very frustrating to say the least.
Is there anything I can help with? I do have several posts on myeloma on my website (just search for “myeloma”) that explain things in (I think) pretty reasonable terms. But if there are specific things you need help with, please feel free to write back and I’ll do my best to explain things.
Best wishes to you both. 🙂
Kristine
I know Jennyne’s post was two years ago, but it seems this post comes up for patients googling for info. If I leave this explanation here it might help the next person.
Bence Jones proteins are the light chains described above, only they’ve spilled over from the blood through the kidneys and are in the urine.
Electrophoresis is a method of separating proteins. They take blood to do the test. The results show the immunoglobulins mentioned above as spikes on a chart (hence M spike). Immunotyping is when they use a second technique on those separated proteins to identify them.