Monoclonal gammopathies: what are they?

Monoclonal gammopathies are diseases of the blood due to deficiencies in the production of immunoglobulins. Keep reading and know what its causes and possible treatments are.

Last update: December 23, 2021

Monoclonal gammopathies constitute a blood diseases set. They are related to deficiencies in the production of immunoglobulins, which are a type of antibodies.

There is a lot of types. Among them is monoclonal gammopathy of uncertain significance (MGUS), which is premalignant. But others, such as multiple myeloma (MM), Waldeström’s macroglobulinemia, and primary amyloidosis are considered malignant.

In many cases, no symptoms are experienced; however, you may also experience bone pain, fatigue, numbness, and a tingling sensation. Treatment and prognosis depend on the type of monoclonal gammopathy and other factors.

What are monoclonal gammopathies?

There are different kinds of blood cells. Among them are those that produce immunoglobulins, which are the proteins responsible for identifying foreign bodies or pathogenic cells, in order to neutralize possible threats.

Each immunoglobulin is made up of two heavy chains and two molecular light chains. But in monoclonal gammopathies, plasma cells produce only one of the chains (heavy or light). This means that the person will have excessive amounts of one type of immunoglobulins or antibodies and others will be deficient.

The cause could not be determined exactly of monoclonal gammopathies, although it is thought that some genetic and environmental aspects may play a role. There are also associated risk factors, such as the following:

  • Sex: more common in men.
  • Age: over 60 years old.
  • Race: more common in Africans and African Americans.
  • Family background.

Types of monoclonal gammopathies

Several types of monoclonal gammopathies are known, the symptoms, treatments and prognoses of which vary. On the one hand, there are those of uncertain significance, which are premalignant disorders, and on the other hand, the malignant ones.

Monoclonal gammopathy of uncertain significance

Monoclonal gammopathy of uncertain significance (MGUS) is also called idiopathic. It is considered the benign form of the disease.

In MGUS there is a protein, known as monoclonal or protein M, which occurs abnormally. However, it is not a major health problem and may not progress to serious forms. Nor does it usually show symptoms.

Appears after age 60. Its prevalence is 1%, although in those over 80 years it increases to 5%. According to studies, it is more common in men.

Multiple myeloma

In multiple myeloma, plasma cells become cancerous. Usually there are bone pain in the skull, ribs, sternum, and vertebrae.

Other common problems in multiple myeloma are anemia and hypercalcemia. According to research, the incidence of multiple myeloma varies between 3 and 4 cases per 100,000, representing 10% of malignant blood diseases and 1% of all neoplasms.

Inside the bone is the bone marrow, where blood components are made. This is why myeloma can present with bone pain.

The chances of developing this disease increase with age.

Waldeström macroglobulinemia

Waldenström macroglobulinemia is also called lymphoplasmacytic lymphoma. It is a type of neoplasm in which there is a monoclonal proliferation of B lymphocytes that infiltrate the bone marrow. It is very rare. It usually affects more men (70% of cases) of advanced age (over 70 years).

In some cases it is asymptomatic, although it can cause hyperviscosity syndrome and coagulation disorders. Among the most common symptoms are the following:

  • Fatigue.
  • Weightloss.
  • Swollen glands.
  • Hepatomegaly and splenomegaly.

Primary amyloidosis

Primary amyloidosis is also a type of cancer. It is not very frequent and its evolution is slow.

It predominantly affects men over 65 years of age. In this disease there are fibrillar proteins (amyloid substances), which accumulate in the tissues.

However, When sufficient amounts of amyloid have been deposited, the function of the affected organ deteriorates, be it kidney, heart even nerves. Symptoms are nonspecific, with diarrhea, fatigue, edema, dyspnea, hypotension, weight loss, and liver inflammation.

Diagnosis of monoclonal gammopathies

More than half of the time, the diagnosis of monoclonal gammopathies occurs by chance, while doing blood tests to detect any other pathology.

Once its presence is determined or suspected, further tests are recommended to confirm. These include the following:

  • Urine, bone marrow and blood tests.
  • Resonances
  • Positron emission tomography.

At GMSI, positive diagnosis is based on the presence of monoclonal immunoglobulin less than 30 grams per liter (g / L) and bone marrow plasma cells by an average below 10%.

In the case of multiple myeloma, in addition to the tests mentioned, a myelogram is done to confirm the presence of abnormal plasma cells, as well as radiology and bone scan to evaluate bone damage.

On the other hand, in Waldeström macroglobulinemia, a bone marrow biopsy is performed, where the lymphomatous infiltration of abnormal cells is observed. And a proteinogram to demonstrate the monoclonal component.

Finally, in the case of primary amyloidosis, since the diagnosis requires the demonstration of amyloid material deposited in the organs, a subcutaneous fat biopsy is performed.

Treatment of monoclonal gammopathies

Treatment varies by type, although in some cases no boarding required. This occurs in monoclonal gammopathies of uncertain significance, as well as in incipient or asymptomatic forms of Waldenström’s macroglobulinemia. However, its evolution must be observed and evaluated through routine controls.

In multiple myeloma, treatments are based on corticosteroids and chemotherapeutic (alkylating) agents. Although these continue to be used, other drugs from the immunomodulatory and proteasome inhibitor families have been added.

In the case of Waldeström’s macroglobulinema, treatment is required when symptoms occur, such as recurrent fevers, weight loss, hyperviscosity syndrome, coagulation disorders, lymphadenopathy and kidney failure.

A combination of several drugs, such as rituximab, alkylating agents, and purine analogs, is often used for this. On the other hand, when there are symptoms of hyperviscosity, plasmapheresis is applied; a method of drawing blood and separating plasma and red and white blood cells.

The only curative treatment for Waldenström’s macroglobulinemia is hematopoietic transplantation. This also applies to multiple myeloma and amyloidosis. However, the advanced age of many patients and the toxicity of the procedure prevent it from always being applied.

Finally, in amyloidosis, possible treatments include drugs such as specific corticosteroids, associated with cyclophosmide and thalidomide. Dexamethasone can also be given with melphalan.

Biopsies and blood tests allow for accurate diagnoses, although sometimes this happens by chance.


A percentage of cases of monoclonal gammopathy (between 12% and 25%) progress to multiple myeloma. The only way to know if it is benign or not is to keep a check on the abnormal monoclonal antibody.

On the other hand, multiple myeloma is still an incurable disease. And while it responds to treatment, in most cases patients will need to be re-treated as they will relapse.

Only a small proportion (about 10%) will have an optimal response and will not get sick again.

For patients with Waldenström macroglobulinemia, this prognosis is conditioned by several factors, such as the patient’s age. In some cases, the disease is stable or slowly progressive; in others it is faster.

And in primary amyloidosis, it all depends on which organs are affected. But if the treatment is not able to reverse the effect of the material deposits in the organs, the prognosis is not very favorable.

Possible risks and complications

Monoclonal gammopathies are usually not curable. In this sense, the purpose of the aforementioned approaches is to improve symptoms and prevent the progression of the disease.

While some gammopathies are stable for a long time, there can also be risks and complications:

  • They interfere with the functioning of the kidneys.
  • Due to the lack of immunoglobulins, the development of infections is favored.
  • Bone pain and fractures can occur.
  • Myeloma affects how the bone marrow works.
  • There may be decalcification of the bones and increased calcium in the blood (hypercalcemia).

Respiratory tract infections are usually the most easily spread by these patients. This means that should take extreme hygiene, avoiding contact with sick people, washing hands well and using masks.

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