BETA - What is a Serum Protein Electrophoresis (SPEP)?

Multiple myeloma is a cancer of plasma cells. Plasma cells are a type of white blood cell that play a key role in the immune system. Their main job is to produce antibodies, which are specialized proteins that help the body fight infections. In multiple myeloma, plasma cells become cancerous and often produce large amounts of a single abnormal antibody, called an M protein or monoclonal protein, which can be detected in blood tests like serum protein, electrophoresis or SPP. But what does this test actually measure and why is it so important? In this video, we'll take a closer look at how S-PEP works, how it detects abnormal monoclonal proteins, also known as M proteins, para proteins, or a M spike, and what the results can reveal about disease burden and progressions. What are myeloma proteins? When we look at multiple myeloma, one of the first questions we ask is which type of protein this myeloma produces. Under normal circumstances, our body has this part of our immune system, the plasma cells that produces antibodies that help you fight off infections. Interestingly, if you look at the human body, about two-thirds of the plasma cells that exist in the human body exist in the gut and they're mostly IgA. But when we look at multiple myeloma, most of the time, myeloma arises from the bone myeloma. This is incredibly rare that it would start from the gastrointestinal tract that we know of. And the majority of cases are of the IgG type, you know, at least 60% of cases. Then you have, you know, 60-70% of cases, you have 30% of cases that are of the IgA type. And then a smaller percent will not produce what we call a heavy chain. Let me explain this, how this works. When you look at the immunoglobulin molecule that I mentioned, for instance, an IgG, it is a foursome. So it always circulates like a foursome. You have two big chains, that long chains, we call them the heavy chains, which in the case of the IgG, they are of the G type or the gamma type. And then you have attached to them two smaller ones, which are the light chains, which can be the kappa or the lambda. And the plasma cells in our body are actually pretty efficient. They produce almost just the right amount. So you have that foursome there and there's not a lot of leftover trimmings, if you may say so. And that's how those circulate in our blood. The same is true for the way IgA starts, it's two big A's and then two little ones. And, you know, the cell that's producing that will usually use only one, the kappa or the lambda. And, you know, that's how they commit to producing that specific antibody. Now, myeloma is the malignant transformation of those cells that were part of our normal immune system. And if you have your myeloma start from a plasma cell that was IgG kappa, which is the most common version of multiple myeloma, every single myeloma cell will be an IgG kappa producer of that myeloma cell. What does the M mean in M protein or M spike? An M protein, that M is typically standing for monoclonal. Monoclonal means coming from the clone one, coming from the one type of cells. And that's reflecting the fact that the cancer cells are actually coming from one clone, from the general original mother cell. And that's really what the M spike is. Now you'll hear that some people would call that para protein. Para is sort of on the side. So why is it para protein? It's because it runs along the side of where abnormal protein bands should be. Why can the M protein be used as a biomarker to monitor the amount of myeloma in the bone marrow? So myeloma cells themselves are cancer of plasma cells. Plasma cells make antibodies. These cancer cells, they typically will still continue to make protein. That protein is abnormal. It's no longer protecting the body from infection, but the protein is secreted into the bloodstream. Therefore, rather than needing to count the myeloma cells inside the bone marrow because they don't come out to the blood, we now have a tool to be able to measure the abnormal protein in the blood. And that would reflect the amount of the cancer cells in a person. When we look for this abnormal protein, because it's mixed together with other proteins in the blood. So we do a test that separate protein into little bands. And that test is called protein electrophoresis. Can be done on the blood, can be done in the urine. Depending on the type of the abnormal protein that someone's cancer may make, we'll be able to see the band of that protein separate out. If we're using that tool, we can follow treatment response because if we're killing cancer, the protein is going to go down. So you will see that whatever patients in protein was to start out with will be comparing the subsequent number to that one. The word electrophoresis means an electrical separation. Electrophoresis uses an electrical charge to separate proteins into their components. What is a S-PEP? What does it tell us? So S-PEPs is short for Serum Protein Electrophoresis. This is a test that we normally do in people who have multiple myeloma or that we suspect they have multiple myeloma. And what it does is that it identifies proteins in the blood. When we have regular blood tests on an annual physical exam, we check a chemistry panel. In the chemistry panel, it can tell us the total amount of protein and the amount of albumin that our body has. But in the blood, we have many types of proteins that are floating around that we need so that we can survive. Some of those proteins are key to help develop more cells. And some of those proteins are key to develop whether it be antibodies or to help fight infections or to just transmit one thing, a message from one part of the body to the other. But when we do those tests, we can only identify the bulk of the protein. And whenever there's a large amount of protein, we want to try to identify why there's a large amount of protein. So an S-PEP is a blood test that we can do in people who we suspect has an abnormal protein in their blood. It can tell us if this is a particular protein that's being produced in an excess amount or if this is just a very healthy patient that has a lot of proteins in their body because they eat a lot of protein or they're in very good shape. So S-PEP helps identify within all of the proteins that are floating around in the blood, if there is a clone or a subset of those proteins that is abnormally high. And if that is the case, then we can then analyze that with additional tests like the immunofixation or IFIX to then label that and determine if that abnormal amount of protein is caused by one particular protein or if it's just a reactive protein. So an S-PEP basically tells us if there is a large quantity of a protein in the blood and how much quantity it is, but it does not have the ability to tell us if this protein is a side effect of inflammation, of an immune reaction, of a rheumatologic disorder, or a clonal process like a cancer or multiple myeloid. We take a small amount of the patient's serum, so that's a liquid part of your blood. We take a blood sample, they spin it, we get the liquid part, and then they put it in a machine that contains a gel. They drop a tiny amount of that blood and then they apply a current that pulls the proteins. As those proteins are pulled in that gel, that allows them to be separated into different compartments or different bands, if you may. And what people do next, they apply a dye that will stain all proteins and then you take a picture of that. I'm simplifying a very complex process, this is done with sophisticated laboratory equipment, but what it allows you to do is to look at the different components of the proteins in a person's blood. In the situation of multiple myeloma, most often we're interested in that area where the immunoglobulins or the monoclonal proteins will be. That is in most patients in the gamma region. There are some patients that have the proteins, what we call migrate or move to other regions, for instance like the beta region, but for the most part we look at the gamma region. Now normally a pathologist, when they see the gamma region, they all see a very nice distribution, what we call a broad-based little lump there that has all the different antibodies that a normal person would have, individuals without multiple myeloma. But if you have myeloma, what we often find is that there's a spike or there's a sharp increase in the concentration of one of those proteins and that's what's called an M-spike. A common misconception is that an M-spike should not be considered synonymous with IgM. M-spike stands for monoclonal or myeloma. The second misconception is the gamma region just tells you where it goes. It is not an IgG. So those are two very important points that often get confused. With this protein electrophoresis you can detect that and you can measure it, so you can use it for diagnosis and you can use it for monitoring, both for treatment as well as the possibility of recurrence or relapse. Now it only tells you there's an abnormal protein but it really doesn't tell you any more about that other than the quantity. But that is in a nutshell what the serum protein electrophoresis is. The immune system is equipped to hopefully be there to give us all kinds of defense depending on what comes our way. So our plasma cells during the process of them growing and become plasma cells, they have gone through a process where they're actually able to intrinsically make multiple, the plasma cells are making unique antibodies that are multiple clones, meaning that well rather than having just one kind of soldiers and all of the soldiers are doing the same thing, you're having your soldiers that are all targeted different things as a basic defense. The monoclonal plasma cells, which is exactly what eventually lead to multiple myeloma though, reflect one of those normal cells have gone through transformation. They've become malignant. So what happened? They don't die off. They can grow and expand and they give rise to the daughter cells that look like that original cells. Those daughter cells keep dividing. That create a clone that all of the daughter cells are actually marked for that same lineage rather than the normal plasma cells, which should just be multiple lineages. That's really their function. Otherwise, we would only be able to fend for one infection and then leave ourselves vulnerable for many others. So those would be typically polyclonal. And this also I think bring up a question in that some patients would have that protein electrophoresis because their doctors are concerned that their total blood protein is elevated. In some, what comes back is polyclonal, meaning that there's whatever reason the immune system is turned on. Every bits of different antibodies are being made in higher amount. It doesn't mean that those people have abnormal plasma cells. It is a point of confusion because some people are worried that they have cancer when they may be having other explanations for that abnormal results. There's something that can happen, however, that's very important for our viewers to understand is that sometimes in the process of cells become cancerous, they can go through secondary changes. So one of the genetic changes that they can go through is that they decide, I'm just going to delete or mutate the heavy chain. So I may go from IgG kappa to kappa only. Now we think that most patients will start with kappa only where IgA or IgG kappa and then the cells got rid of that heavy chain gene and then just became kappa or lambda, whatever the gene was. And that's what we call light chain multiple myeloma. Now there's a tiny fraction of myelomas that don't produce heavy chains, don't produce light chains, and there's called the non-secretors. It's a whole other topic of what non-secretors mean. Some patients, the cells produce a little protein, but they don't put it out into the blood. Some of them don't produce proteins at all. And we don't have very good markers for their detection. If your myeloma cancer cells don't secrete a lot of M protein, can a S-PEP still be used? You hit the right place in that unfortunately some of these cancer cells, they actually either not secrete a whole lot of abnormal protein for us to see or it's actually retained within the cancer cells themselves. That group of patients, we call them non-secretory. What does it mean? It means that there's not going to be a simple blood test. This protein electrophoresis that we can use in some patients, we will utilize a similar free light chain that's a bit more sensitive. It will pick up some of these cases that we don't see in protein, but there's still some patients that even those available tests, we can't use them. Those are a group of patients that we try to use some other ways to monitor their treatment response. Typically, I'll incorporate the whole body imaging, a PET scan for example, because it'll give me a sense of those areas of hot spots. Also, we'll incorporate the bone marrow as a patient in biopsy and fortunately, that's a bit more invasive. So some of these patients will have the bone marrow test every three to six months. We can't do it every month, unlike the blood test, which is so much simpler. But the hope though is that there are newer technologies now that hopefully will help this particular group of patients in addition to helping everyone else. Technology like measuring the DNA from the tumor cells in the bloodstream. It's really coming right along. There's also a different technique to try to look for a very rare protein in the blood called mass spectrometry. And that test, it's more sensitive than the protein electrophoresis or even the light chain. It may actually allow us a better way to still help those patients without needing to do bone marrow all the time. Monoclonal proteins are a key marker of myeloma produced by malignant plasma cells, not healthy ones. Understanding the difference helps doctors diagnose and monitor the disease more accurately. The more you know about how myeloma works, the more empowered you are to be part of your care journey. Thanks for watching and be sure to check out our other videos to keep learning.