Heavy chain diseases are plasma cell cancers in which a clone of plasma cells produces a large quantity of pieces of abnormal antibodies called heavy chains.
(See also Overview of Plasma Cell Disorders.)
Plasma cells develop from B cells (B lymphocytes), a type of white blood cell that normally produces antibodies (immunoglobulins). Antibodies are proteins that help the body fight infection.
If a single plasma cell multiplies excessively, the resulting group of genetically identical cells (called a clone) produces a large quantity of a single type of antibody. Because this antibody is made by a single clone, it is called a monoclonal antibody and also is known as the M-protein. People with a large quantity of the M-protein often have reduced levels of other antibodies. In some cases, the antibody produced is incomplete, consisting of only light chains or heavy chains (functional antibodies normally consist of 2 pairs of 2 different chains called a light chain and heavy chain).
There are 5 classes of antibodies— IgM, IgG, IgA, IgE, and IgD. Each class has its own type of heavy chain. In heavy chain diseases, a plasma cell clone produces a single type of abnormal heavy chains without their corresponding light chains.
The main heavy chain diseases are categorized according to the type of heavy chain produced:
Alpha (from IgA)
Gamma (from IgG)
Mu (from IgM)
Alpha Heavy Chain Disease
Alpha heavy chain disease (IgA heavy chain disease) affects mainly younger adults of Middle Eastern or Mediterranean ancestry. Infiltration of the intestinal tract wall by cancerous plasma cells often prevents proper absorption of nutrients from food (malabsorption), resulting in severe diarrhea and weight loss. A rare form affects the respiratory tract.
Doctors do blood tests when they suspect alpha heavy chain disease. Such tests include serum protein electrophoresis (SPEP), immunoelectrophoresis, and measurement of immunoglobulin levels (immunofixation). SPEP is a test that measures specific proteins in the plasma to help identify some diseases. Immunofixation is a more specialized version of this test, in which proteins are separated out and identified based on the detectable immunologic reactions they produce.
Urine tests may also be needed. Sometimes tissue from the intestine is removed and examined (biopsy).
Gamma Heavy Chain Disease
Gamma heavy chain disease (IgG heavy chain disease) affects mainly older men. Some people with gamma heavy chain disease have no symptoms. Some people also have other immune system disorders such as rheumatoid arthritis, Sjögren syndrome, or systemic lupus erythematosus (lupus).
Infiltration of the bone marrow by cancerous plasma cells causes some people to have symptoms of recurring infections, such as repeated episodes of fever and chills associated with a decreased number of white blood cells, and fatigue and weakness associated with severe anemia. Cancerous plasma cells may also enlarge the liver and spleen.
Blood and urine tests are needed to make the diagnosis.
People with symptoms may respond to chemotherapy agents, corticosteroids, and radiation therapy. But gamma heavy chain disease usually progresses rapidly, and about half of affected people die within about a year.
Mu Heavy Chain Disease
Mu heavy chain disease (IgM heavy chain disease), the rarest of the 3 main heavy chain diseases, most often affects people over 50. It may cause enlargement of the liver and spleen as well as enlargement of the lymph nodes in the abdomen. Fractures and amyloidosis may also occur.
Blood and urine tests are typically done. Bone marrow examination is usually needed for diagnosis.
Treatment usually includes chemotherapy agents and corticosteroids. Length of survival and response to treatment vary widely.
