Multiple Myeloma Immunoglobulin and Its Significance

Multiple myeloma is a blood cancer that originates in plasma cells, a type of white blood cell found in the bone marrow. Healthy plasma cells are part of the immune system and produce proteins called immunoglobulins, or antibodies, which help the body fight infections. In multiple myeloma, plasma cells become cancerous, multiply uncontrollably, and disrupt the normal production of blood cells.

The Basics of Immunoglobulins

Immunoglobulins are proteins produced by plasma cells to protect against invaders like viruses and bacteria. They function by recognizing and binding to specific molecules on these invaders, called antigens, which tags them for elimination. This process is part of the adaptive immune response, allowing the body to remember and more effectively fight previous infections.

An immunoglobulin has a Y-shaped structure composed of two identical heavy chains and two identical light chains linked together. The tips of the “Y” contain the variable regions that bind to antigens. The stem, or constant region, determines the antibody’s class and its role in the immune response.

There are five main classes of immunoglobulins in a healthy person: IgG, IgA, IgM, IgD, and IgE. IgG is the most abundant antibody in the blood and provides the majority of immunity against pathogens. IgA is concentrated in secretions like saliva and mucus, where it guards entrances to the body.

IgM is the first antibody produced in response to a new infection and activates other parts of the immune system. IgE is involved in allergic reactions and defense against parasites. IgD is found on the surface of B-cells and acts as an antigen receptor.

M-Proteins: The Hallmark of Multiple Myeloma

In multiple myeloma, cancerous plasma cells originate from a single abnormal cell. They produce massive quantities of a single, identical, and non-functional immunoglobulin, or a fragment of one. This abnormal protein is known as a monoclonal protein, or M-protein.

The presence of M-protein in the blood or urine is a primary tumor marker for the disease. These proteins are ineffective at fighting infection. Their high numbers also crowd out the production of normal antibodies, which leaves the patient vulnerable to illness.

M-proteins are classified based on the type of heavy and light chains they contain, such as IgG or IgA. The light chains are either kappa or lambda. IgG is the most common type of M-protein in myeloma patients, followed by IgA. In some cases, known as light chain myeloma, the cancerous cells only produce the light chain portion. These free light chains are called Bence-Jones proteins and can be detected in the urine.

Identifying and Quantifying Myeloma-Related Immunoglobulins

Detecting and measuring M-proteins and free light chains is used to diagnose multiple myeloma, track its progression, and monitor response to treatment. A panel of laboratory tests measures the byproducts of the cancer cells.

• Serum Protein Electrophoresis (SPEP) separates proteins in a blood sample, where the large quantity of M-protein appears as a distinct “M-spike.”
• Urine Protein Electrophoresis (UPEP) is a similar test that detects M-proteins and free light chains (Bence-Jones protein) in the urine.
• Immunofixation Electrophoresis (IFE) is used after SPEP to identify the specific heavy and light chain components of the M-spike.
• The Serum Free Light Chain (SFLC) assay measures the levels of unattached kappa and lambda light chains in the blood, and an abnormal ratio is a sensitive indicator of a plasma cell disorder.
• Quantitative immunoglobulin tests measure the total levels of normal IgG, IgA, and IgM, which are often suppressed in myeloma.

Interpreting Immunoglobulin Levels in Multiple Myeloma

The quantity of M-protein in the blood or urine correlates with the number of cancerous plasma cells, known as the tumor burden. These measurements are used in diagnosis and help differentiate multiple myeloma from precursor conditions. For instance, Monoclonal Gammopathy of Undetermined Significance (MGUS) involves a small M-protein level without symptoms, while smoldering multiple myeloma has higher levels but lacks organ damage.

Monitoring M-protein and free light chain levels over time is a standard practice in managing the disease. A decrease in these markers following therapy indicates a positive response. Conversely, a rise in these levels can signal that the disease is progressing or has relapsed, allowing for timely adjustments to treatment plans.

The specific type and amount of immunoglobulin can also offer prognostic information. For example, IgA myeloma can be associated with a more aggressive disease course than IgG myeloma. High levels of M-protein or a highly abnormal free light chain ratio at diagnosis can suggest a greater tumor burden.

The abnormal immunoglobulins themselves are directly responsible for some of the most serious complications of multiple myeloma. Excess free light chains are particularly damaging to the kidneys, where they can accumulate and form blockages, a condition that can lead to kidney failure. Additionally, high concentrations of M-protein can thicken the blood and impair circulation, causing a dangerous condition called hyperviscosity syndrome.