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Paraproteinemia is the presence of elevated levels of paraproteins or monoclonal gammaglobulins in the blood, which is why it's also called monoclonal gammopathy. It usually occurs as a part of immunoproliferative disorders such as leukemias, lymphomas, and plasma cell dyscrasia or cancers. This condition may also be a manifestation of a disease without a known cause, such as monoclonal gammopathy of undetermined significance. Diagnosis depends on the detection of abnormal immune proteins in the blood, and treatment involves management of the underlying cause.
This condition occurs due to the presence of elevated amounts of a single monoclonal gammaglobulin in the blood. A monoclonal gammaglobulin, also called a paraprotein, comes from a single parent cell through multiple replications; therefore, paraproteins are essentially clones of each other. Monoclonal cells are characteristic of cancer cells. A type of B cell called a plasma cell produces gammaglobulins, so excessive monoclonal gammaglobulins in the blood signifies an aberration in the replication of plasma cells. For this reason, it is expected that leukemias and lymphomas, such as B cell non-Hodgkin lymphomas, lead to paraproteinemias.
Gammaglobulins have light chains and heavy chains, such that paraproteinemias are classified into three types according to what type of chain is predominant. Light chain paraproteinemia occurs in amyloid light chain (AL) amyloidosis. AL amyloidosis occurs in about 5 to 15% of multiple myeloma patients. Heavy chain disease indicates immunoglobulin heavy chains. Gamma heavy chain disease or Franklin’s disease features fever, anemia, body malaise, weakness, enlargement of lymph nodes, and enlargement of the liver and spleen.
The third type involves whole immunoglobulins, wherein there is an abnormal ratio of light chains to heavy chains. In general, when monoclonal gammopathy involves heavy chains or whole immunoglobulins, the paraproteins are retained within the blood vessels. Sometimes, whole immunoglobulins aggregate and form polymers, leading to a condition called macroglobulinemia. With macroglobulinemia, the blood becomes more viscous and tends to resist flow, a condition that occurs in the disease called Waldenström macroglobulinemia or lymphoplasmacytic lymphoma.
When the gammopathy involves light chains, the paraproteins escape from the blood vessels and become excreted by the kidneys. When a sample of urine is examined under the microscope, they are observed in the form of Bence Jones protein. Bence Jones proteins can serve as a clue to the diagnosis of multiple myeloma or Waldenström macroglobulinemia.
Paraproteinemia is diagnosed through serum protein electrophoresis, which typically shows a spike or a narrow band that indicates the overproduction of a certain protein. In electrophoresis, globulins are separated into alpha, beta, and gamma bands. The paraproteins manifest as a spike in the gamma band. Successful treatment of the underlying disorder, such as through chemotherapy or radiation therapy, is needed to treat this condition.
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