Paraproteinemia

Overview
Paraproteinemia (also known as "monoclonal gammopathy") is the presence of excessive amounts of a single monoclonal gammaglobulin (in this case denominated "paraprotein") in the blood. It denotes an underlying immunoproliferative disorder.

Types
Paraproteinaemias may be categorised according to the type of monoclonal protein found in blood:


 * Light chains ("Bence Jones protein") only;
 * Heavy chains only;
 * Whole immunoglobulins (albeit often with an abnormal light / heavy chain ratio). In this case, the paraprotein goes under the name of "M-protein" ("M" for monoclonal). If immunoglobulins tend to precipitate within blood vessels with cold, that phenomenon takes the name of cryoglobulinaemia.

Possible causes

 * Leukaemias and lymphomas of various types.
 * Myeloma
 * Waldenström macroglobulinemia (IgM only)
 * Amyloidosis (either light or heavy chains only)

If no cause is identified, the term "monoclonal gammopathy of undetermined significance" is used.

Diagnosis
These disorders are characterized by the presence of any abnormal protein that is involved in the immune system, which are most often immunoglobulins and are associated with the clonal proliferation of lymphocytes.

When a paraproteinemia is present in the blood, there will be a narrow band, or spike, in the serum protein electrophoresis because there will be an excess of production of one protein.

There are two large classes of blood proteins: albumin and globulin. They are generally equal in proportion, but albumin is much smaller than globulin, and slightly negatively charged, which leads to an accumulation at the end of the electrophoretic gel. The globulins separate out into three regions on the electrophoretic gel, which are the α band, the β band, and the γ band.


 * The α band can be separated into two components: α1 and α2. The α1 region consists mostly of α1-antitrypsin and α1-acid glycoprotein. The α2 region is mostly haptoglobin, α2-macroglobulin, α2-antiplasmin and ceruloplasmin.


 * The β band consists of transferring, low density lipoproteins, and complement system proteins.


 * The γ band is where the immunoglobulins appear, which is why they are also known as gammaglobulins. The majority of paraproteins appear in this band.

Differential Diagnosis of Causes of Paraproteinemia

 * Amyloidosis
 * Benign gammopathy
 * Bronchial carcinoma
 * Chronic Idiopathic Cold Agglutinin Disease
 * Cirrhosis
 * Cryoglobulins
 * Franklin's disease
 * Malignant Melanoma
 * Monoclonal gammopathy of unclear origin
 * Multiple Myeloma
 * Prostate carcinoma