What Is the Most Common Cause of Monoclonal Gammopathy?

Medically Reviewed on 2/15/2023
Causes of Monoclonal Gammopathy
Monoclonal gammopathy can be benign or it can be a sign of a blood cancer called multiple myeloma.

Monoclonal gammopathy (MG) refers to the presence of abnormal proteins called monoclonal proteins (antibodies) or M proteins in the blood. These proteins are produced by a type of white blood cell called plasma cells. 

The most common cause of MG is multiple myeloma, a type of cancer affecting the plasma cells in the bone marrow. Other less common causes of MG include a type of lymphoma called Waldenström macroglobulinemia and primary amyloidosis, which is a rare disorder in which abnormal proteins called amyloids accumulate in the body's organs and tissues.

Moreover, MG can occur due to other types of cancer or as a side effect of certain medications. In some cases, the cause of MG is unknown.

What causes monoclonal gammopathy?

Different causes of monoclonal gammopathy (MG) may include:

  • Multiple myeloma: A type of cancer affecting the bone marrow's plasma cells. It is the most common cause of MG.
  • Monoclonal gammopathy of undetermined significance (MGUS): A condition in which a small amount of an M protein is present in a person’s blood, but they do not have any symptoms or signs of multiple myeloma or any other related cancer. It is not clear what causes MGUS, but it is thought to be related to changes in the DNA of plasma cells.
  • Waldenström macroglobulinemia: Rare cancer affecting the plasma cells in the bone marrow. It is characterized by the production of an M protein called an immunoglobulin M protein.
  • Amyloidosis: A rare condition in which abnormal proteins called amyloids are deposited in various tissues and organs, including the kidneys, heart, and nervous system. It can be caused by various conditions, including multiple myeloma and other types of cancer.
  • Lymphoproliferative disorders: A group of conditions that involve the abnormal growth and proliferation of lymphocytes, a type of white blood cell. These disorders can cause the production of an M protein.
  • Autoimmune disorders: In some cases, MG can be caused by autoimmune disorders, such as rheumatoid arthritis or lupus.
  • Infections: Some infections, such as hepatitis B and C, can lead to the production of abnormal monoclonal antibodies.
  • Medications: Certain medications, such as procainamide and hydralazine, have been linked to the development of MG.

In some cases, the cause of MG is unknown. If you have been diagnosed with this disorder, it is important to discuss the potential causes and treatment options with your healthcare provider.

Who is at a risk of monoclonal gammopathy?

Monoclonal gammopathy (MG) can be benign (noncancerous) or it can be a sign of a blood cancer called multiple myeloma. Having one or more of these risk factors does not necessarily mean that a person will develop MG. The condition is relatively rare, and the exact causes are not fully understood.

Risk factors for MG include:

  • Age: The risk of MG increases with age, with most cases occurring in people older than 50 years.
  • Gender: Men are more likely to develop MG than women.
  • Family history: People with a family history of MG or multiple myeloma may be at an increased risk of developing the condition.
  • Genetic factors: Certain genetic mutations have been linked to an increased risk of MG, including mutations in the TP53 gene.
  • Exposure to certain chemicals: Some studies have suggested that exposure to certain chemicals, such as benzene or herbicides, may increase the risk of MG.
  • Certain medical conditions: People with certain medical conditions, such as rheumatoid arthritis or lupus, may have an increased risk of MG.
  • Certain medications: Taking certain medications, such as proton pump inhibitors, nonsteroidal anti-inflammatory drugs, immunosuppressants, and chemotherapeutic agents, may increase the risk of MG.

MG is a relatively rare condition, and most people with monoclonal proteins in their blood do not develop any serious health problems. However, it's important to speak with a healthcare provider if you have concerns about your risk of developing MG.

What are the common signs and symptoms of monoclonal gammopathy?

Several signs and symptoms may be associated with monoclonal gammopathy (MG). Not everyone with MG will experience symptoms, and the severity of the symptoms can vary widely from person to person.

Common signs and symptoms of MG include:

These symptoms can be caused by other conditions and do not necessarily mean that you have MG. If you experience any of these symptoms, it is important to speak with a healthcare provider to determine the cause.


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How is monoclonal gammopathy diagnosed?

Monoclonal gammopathy (MG) is diagnosed through a combination of medical history, physical examination, and laboratory testing. 

  • Medical history: The first step in diagnosing MG is taking a detailed medical history. This includes asking about any symptoms the person may be experiencing, any past medical conditions, or medications they are taking.
  • Physical examination: The healthcare provider will perform a physical examination to look for any signs of MG, such as swollen lymph nodes or an enlarged spleen.
  • Laboratory testing: To confirm the diagnosis of MG, laboratory testing is required. This may include a complete blood count to measure the levels of various types of cells in the blood and a blood chemistry panel to measure the levels of proteins and other substances in the blood.
  • Serum protein electrophoresis: This test separates proteins in the blood based on their size and charge and can help identify the presence of a monoclonal protein.
  • Urine protein electrophoresis: This test is similar to serum protein electrophoresis, but it looks for monoclonal proteins in the urine.
  • Immunofixation: This test identifies the type of monoclonal protein present in the blood or urine.
  • Bone marrow biopsy: In some cases, a bone marrow biopsy may be performed to determine if the monoclonal protein is being produced by cancerous cells in the bone marrow.

What are the treatment options for monoclonal gammopathy?

Treatment options for monoclonal gammopathy (MG) depend on the type of disorder and its severity, age, and underlying medical condition (if any) of the individual.

Common treatment options for MG include:

  • Observation: If MG is mild or asymptomatic, your healthcare provider may recommend observation without treatment. This involves regularly monitoring your condition to see if it progresses or if any symptoms develop.
  • Chemotherapy: Involves using drugs to kill cancer cells or stop them from growing. It is often used to treat multiple myeloma and can be given intravenously or orally.
  • Immunomodulatory agents: These drugs help boost the immune system and are often used in combination with chemotherapy to treat multiple myeloma.
  • Monoclonal antibody therapy: Involves using drugs that target specific proteins on the surface of cancer cells. 
  • Steroids: These drugs can help reduce inflammation and suppress the immune system. They may be used in combination with other treatments for MG.
  • Plasma exchange: This involves removing plasma (the liquid part of the blood) from the body and replacing it with a solution to help remove the abnormal proteins. 
  • Stem cell transplantation: Involves high doses of chemotherapy or radiation to kill cancer cells, followed by a transplant of healthy stem cells to help the body regenerate new blood cells.
  • Radiation therapy: Involves using high-energy beams, such as X-rays, to kill cancer cells or shrink tumors. It may be used to treat localized areas of cancer or to relieve symptoms caused by multiple myeloma.
  • Surgery: May be used to remove tumors or correct MG complications, such as bone fractures.

The treatment plan for MG will be individualized based on the specific type of disorder and the severity of the condition. Your healthcare provider will work with you to determine the most appropriate treatment plan for your specific needs.

What are the potential complications of monoclonal gammopathy?

There are several potential complications associated with monoclonal gammopathy (MG), including the following:

  • Multiple myeloma: This type of cancer develops from plasma cells and is characterized by the production of an abnormal monoclonal protein (M protein). Multiple myeloma can cause bone lesions, kidney damage, anemia, and an increased risk of infections.
  • Amyloidosis: A condition in which the M protein forms clumps called amyloid deposits, which can build up in various organs, including the heart, liver, and kidneys. This can lead to organ damage and failure.
  • Waldenström macroglobulinemia: This type of lymphoma (cancer of the immune system) is characterized by the production of an M protein called immunoglobulin M. It can cause anemia, fatigue, and an increased risk of bleeding and infections.
  • Cryoglobulinemia: A condition in which M proteins in the blood form clumps when exposed to cold temperatures. These clumps can block small blood vessels, leading to symptoms such as joint pain and numbness in the hands and feet.
  • Hyperviscosity syndrome: This is a condition in which the M protein concentration in the blood is very high, resulting in thick, sticky blood that can lead to circulation problems. Symptoms may include dizziness, headaches, and visual changes.
  • Bone marrow suppression: In some cases, MG can lead to a reduction in the production of normal blood cells in the bone marrow, resulting in anemia, fatigue, and an increased risk of infections.

Not all individuals with MG will develop these complications. The risk of complications depends on the type and severity of the MG. The outcome for people with MG can vary depending on the type and severity of the condition. Some people with benign MG may not need any treatment and can live normal lives. Others may need to be monitored regularly for any changes in their condition.

For those with more serious conditions, such as multiple myeloma, the outlook can be more uncertain. With proper treatment, many affected individuals can live for several years with a good quality of life. However, some complications can be progressive and life-threatening, and affected individuals need to work closely with their healthcare team to manage their condition and address any symptoms or complications that may arise.

Medically Reviewed on 2/15/2023
Image Source: iStock image

What is the significance of monoclonal gammopathy of undetermined significance? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334115/

Diagnosis and Management of Monoclonal Gammopathy and Smoldering Multiple Myeloma https://jnccn.org/view/journals/jnccn/18/12/article-p1720.xml

Diagnosis of Monoclonal Gammopathies https://arup.utah.edu/media/gammopathies/2011%20Jan%20-%20Monoclonal%20Gammopathies.pdf

Monoclonal gammopathy and primary care https://bcmj.org/articles/monoclonal-gammopathy-and-primary-care