Some multiple myeloma grows slowly and stays quiet. Other cases move faster and cause problems sooner. Many people are surprised to learn that the type of antibody (immune protein) made by myeloma cells can affect how active the disease is. Different antibody types behave in different ways, so certain forms of this blood cancer are more aggressive than others.

This article looks at why antibody types matter in myeloma and which ones tend to be more aggressive. We’ll start with some basics about plasma cells and then explain what doctors know about how fast each type grows, how the cancer spreads, and how likely it is to return after treatment.

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Plasma Cells and Antibodies

Your immune system has many tools to keep you safe. One of the most important is the plasma cell, a type of white blood cell that lives in your bone marrow. Plasma cells make proteins called antibodies — also called immunoglobulins (Igs) — that help your body find and fight germs.

In multiple myeloma, plasma cells turn cancerous. These abnormal cells grow too fast and make large amounts of a single, faulty antibody called monoclonal protein (M protein). M protein can’t fight infection. Instead, it builds up in the blood or urine and may damage organs. Testing for these abnormal antibodies helps doctors diagnose myeloma and plan treatment.

What Are Antibodies?

Antibodies are proteins that help protect the body from harmful invaders such as bacteria, viruses, and allergens. In a healthy immune system, antibodies attach to these threats and signal the rest of the immune system to destroy the germ or remove the foreign substance.

Healthy plasma cells produce antibodies that fight infections. Myeloma cells produce large quantities of abnormal antibodies that don’t work properly.

Each antibody can recognize only one specific target (antigen) on a particular bacterium, virus, or other substance. Usually, the body has many different plasma cells, each of which makes antibodies with a different target. Together, these antibodies can recognize a wide variety of substances. Some plasma cells live a long time and help the body “remember” past infections.

Types of Antibodies

Each antibody is made up of four smaller proteins — two light chains and two heavy chains. The type of heavy chain determines the kind of antibody. The light chains, called kappa or lambda, add more detail. Testing for these chains helps doctors learn which immunoglobulin your myeloma cells are making.

There are five main types of antibodies:

• IgG — The most common type, IgG, is found in the blood and body fluids and helps protect against everyday infections. IgG also provides immunological memory to fight off infections you’ve had before.
• IgA — Found in mucosal areas like the mouth, nose, lungs, and gut, IgA helps stop germs before they enter the body.
• IgM — This is the first antibody made when the body responds to an infection.
• IgE — This antibody triggers allergic reactions in the skin, lungs, and tissues that line the body.
• IgD — Found on the surface of certain immune cells, IgD may help start the production of IgM antibodies, but its exact role isn’t fully understood.

What Are the Types of Multiple Myeloma?

Like normal antibodies, M protein consists of two heavy-chain and two light-chain proteins. Multiple myeloma is classified based on the type of chain that makes up the M protein. Different types can behave differently and may need different treatment plans.

The most common subtype is IgG myeloma, which affects about two-thirds of all people with the disease. IgA myeloma is the next most common, affecting about 1 in 5 people with myeloma. Rarer forms include IgD, IgM, and IgE myelomas. IgD myeloma, in particular, is often linked to plasma cell leukemia. If the M protein is made from IgM heavy chains, the person may have Waldenström’s macroglobulinemia, a type of non-Hodgkin lymphoma.

Some people have light-chain myeloma, also called Bence-Jones myeloma. In this type, the plasma cells make only kappa or lambda light chains, not heavy chains. In a rare type called nonsecretory myeloma, the cancerous plasma cells don’t make any part of the M protein.

How Is Immunoglobulin Type Determined?

During myeloma diagnosis, doctors run blood and urine tests to learn which antibody type — such as IgA, IgG, or another heavy chain — your plasma cells are making. These tests identify the type of M protein and show how much heavy- or light-chain protein is in your body. Knowing your antibody type helps doctors understand how active the cancer is and choose the right treatment.

Read about how maintenance treatment for myeloma helps extend remission.

Tests To Measure IgG and IgA

One key test is immunofixation electrophoresis (IFE). This test looks at a blood or urine sample and identifies which heavy chain is in the M protein. IFE helps confirm your myeloma subtype and, when combined with other tests, can help track your response to treatment.

IgA multiple myeloma behaves more aggressively than other types of myeloma. It grows faster and has a higher risk of relapse.

Another helpful test, quantitative immunoglobulins, measures how much of each antibody is in your blood, including both normal and abnormal levels. This test helps doctors understand how active the myeloma is and how well treatment is working over time. Quantitative immunoglobulin tests are often repeated during follow-up to monitor for changes. However, they’re used less often for long-term tracking because normal antibody levels can make it harder to detect changes in the abnormal M protein.

Measuring M Protein Levels

Once your myeloma type is known, doctors regularly check M protein levels to see how active the disease is. During treatment, changes in these levels help show whether therapy is working.

Two common tests are serum protein electrophoresis (SPEP), which looks at blood, and urine protein electrophoresis (UPEP), which looks at urine. These tests can reveal if M protein is rising or falling. Since IgA can be harder to measure on SPEP, some doctors may also use quantitative immunoglobulins to track IgA myeloma more accurately.

Which Type of Myeloma Is More Aggressive?

Doctors now know that IgA myeloma behaves more aggressively than other types. This means the cancer may grow faster, spread more easily, and lead to a worse overall prognosis (outlook). People with IgA myeloma may have more problems outside the bone marrow, such as soft-tissue growths called extramedullary plasmacytomas. Studies show that IgA myeloma leads to lower long-term survival rates and a higher risk of relapse — meaning the cancer is more likely to return after treatment.

IgA myeloma is also more often linked to cytogenetic abnormalities — genetic changes that can cause the cancer to grow faster or become refractory (resist treatment). Not everyone with IgA myeloma has severe disease, but overall, it tends to grow or spread more quickly than other types, such as IgG myeloma.

If your oncology team believes your multiple myeloma is more aggressive, this may influence the treatment plan they recommend.

Why Is IgA Myeloma More Aggressive?

Researchers are still studying why IgA myeloma tends to be more aggressive, but they’ve discovered several clues. One important finding is that many IgA myeloma cells have low CD56 expression. CD56 is a protein that helps cells stick together inside the bone marrow.

One study found that just over 50 percent of people with IgA myeloma had CD56, compared with 70 percent to 80 percent in other types of myeloma. Without CD56, cells may not stay anchored in the bone marrow. They’re more likely to spread and form extramedullary tumors, which are often linked to more aggressive disease.

If your oncology team believes your multiple myeloma is more aggressive, this may influence the treatment plan they recommend.

The researchers also noted that IgA myeloma is hard to measure on standard blood tests, such as SPEP. When IgA proteins move into a spot called the beta region, they can hide or mask the M protein spike that doctors look for when tracking myeloma. If the main marker is harder to see, the cancer may grow for longer before it’s detected. Together, these factors may help explain why IgA myeloma can be more difficult to track — and more aggressive.

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