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Paraproteinemia can be defined as a medical condition, in which excessive quantities of paraprotein are present in the blood. This condition is also known as monoclonal gammopathy (excessive amounts of monoclonal gammaglobulin in the blood). As you will have the opportunity to read below, this condition is often encountered in those who have been diagnosed with immunoproliferative disorders. The paraproteins are actually immunoglobulins that are produced at the level of the bone marrow and they can cause damage to the kidneys, when excreted in excess through the urine. This condition is more common in the elderly population, rather than the young.

Types of Paraproteinemia

Paraproteinemia can be classified into different types, according to the paraprotein that is found in the blood. These are the three main types of paraproteinemia:

  • Light-chain paraproteinemia (the Bence Jones protein)
    • Often associated with immunoproliferative disorders, such as amyloidosis or multiple myeloma
  • Heavy-chain paraproteinemia
    • This condition is also known as the heavy chain disease
  • Whole-immunoglobulin paraproteinemia
    • M-proteins (monoclonal) are present in the blood
    • The condition can be influenced by the cold, being known as cryoglobulinemia (the immunoglobulins have a tendency to precipitate in the blood vessels, as a result of the cold temperatures)

It is important to understand that the above-mentioned types can appear on their own in an individual or combined. In general, the heavy-chain and the whole immunoglobulin proteins are restricted to the blood vessels. On the other hand, the light-chain immunoglobulins can escape from the blood vessels, being excreted by the kidneys together with the urine (these are known as the Bence Jones proteins).

In some patients, the whole immunoglobulins can bind with one another, leading to a condition known as macroglobulinemia. This condition can aggravate the already existent health problems. As it was already mentioned above, one can suffer from cryoglobulinemia, with the immunoglobulins precipitating in the blood vessels with cold temperatures. It is also possible that the whole immunoglobulins reduce the viscosity of the blood, leading to a condition known as Waldenström macroglobulinemia.


These are the potential causes that lead to the appearance of paraproteinemia:

  • Leukemia and lymphoma
    • B-cell non-Hodgkin lymphoma – type of cancer that derives from the lymphocytes (white blood cell)
    • Myeloma – cancer of the plasma cells, in which abnormal cells collect at the level of the bone marrow and interfere with the production of normal, healthy blood cells
    • Plasmacytoma – malignant plasma cell tumor, occurring either at the level of the soft tissues or within the axial skeleton
    • Lymphoplasmacytic lymphoma – cancer affecting the B white cells, with a tendency of growing and spreading slowly, in a gradual manner
  • Idiopathic (either no cause can be identified or the condition will develop into leukemia or lymphoma in several years)
    • Benign monoclonal gammopathy (also known as monoclonal gammopathy of undetermined significance) – the condition is identified through routine testing and, at first, it might resemble the multiple myeloma
    • Primary amyloidosis (light-chain paraproteinemia) – this is a rare medical condition, in which abnormal proteins accumulate throughout the body (these proteins are also known as amyloids).


These are the most common methods used for the diagnosis of paraproteinemia:

  • Blood testing
    • Serum protein electrophoresis
      • Narrow band or spike – these are because of the excessive amounts of proteins (elevated serum total protein)
    • Serum immunofixation electrophoresis (further testing)
    • Serum free light chain – should be correlated with the urine analysis (24 hour collection)
    • Quantitative immunoglobulins
  • Determination of the hematocrit
  • Blood viscosity analysis – the immunoglobulins present in the blood can increase the level of viscosity
  • Urine analysis – for the best results, a 24-hour collection of urine is required
  • Immunoglobulin levels (IgA, IgG, IgM and IgD) – identification of normal and abnormal proteins
  • Identification of light and heavy chains
  • Other investigations
    • Skeletal investigation or survey
    • Bone marrow biopsy (suspicion of leukemia or lymphoma)
    • CT scan


In order to improve the paraproteinemia signs, the treatment is usually concentrated on the associated disorder. These are the most common treatment approaches that can be taken in such cases:

  • Acute management
  • Supportive care (recommended for the more serious cases)
    • Bone directed therapy
      • Vitamin D and Calcium
      • Bisphosphonates
    • Medication to prevent neuropathy
    • Narcotics and other analgesics for the pain
  • Anti-cancer therapy
    • Radiation therapy
    • Chemotherapy
    • Biologic therapy
    • Autologous transplantation
  • Long-term therapy
    • Specific medication and management
  • Allogeneic transplantation
  • Medication administered in combination with the autologous transplant
  • In case of infections associated with myeloma – antibiotics or antivirals
  • Pain medication – helps the patient deal with the symptomatology
  • Plasma exchange in case of renal insufficiency
  • Corticosteroids – recommended for serious cases
  • Immuno-modulatory drugs – recommended choices: Thalidomide, Pomalidomide and Lenalidomide
  • Proteasome inhibitors – recommended choices: Carfilzomib, Bortezomib
  • Treatment measures for amyloidosis
    • Chemotherapy – targets plasma cells
    • The high-dose chemotherapy might be combined with the autologous stem cell transplantation
    • Anti-inflammatory medication
    • Organ transplantation in case of organ failure
    • Clinical trials – treatments in the experimental phase
  • Other treatments
    • Monoclonal antibodies
    • Immunotherapy
    • Hematopoietic stem cell transplantation

Disorders associated with paraproteinemia

These are the disorders commonly associated with paraproteinemia:


  • Auto-immune disorders – systemic lupus erythematosus, rheumatoid arthritis, Hashimoto’s thyroiditis

Cutaneous disease

  • Pyoderma gangrenosum
  • Liver disease (hepatitis, cirrhosis)
  • Infectious disease (mycobacterium, bacterial endocarditis)


  • Monoclonal gammopathy of undetermined significance


  • Non-Hodgkin lymphoma
  • Waldenström macroglobulinemia
  • Chronic lymphocytic leukemia
  • Amyloidosis
  • Plasma cell leukemia
  • POEMS syndrome
  • Myeloma
  • Solitary plasmacytoma.

In conclusion, paraproteinemia is a medical condition in which the paraprotein levels are elevated. This condition is often found in association with immunoproliferative diseases and especially cancers of the bone marrow. The diagnosis is made through serum electrophoresis and, often times, further methods of investigation are required for the confirmation of such health problems. The treatment is concentrated on the underlying condition and also on improving the survival rate; if the cancer is treated, the paraproteinemia is going to improve as well. However, in many situations, the supportive care might represent the only option.

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