Paraproteinemia
Encyclopedia
Paraproteinemia, or 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.
It is sometimes considered equivalent to plasma cell dyscrasia.
The three types of paraproteins may occur alone or in combination in a given individual. Note that while most heavy chains or whole immunoglobulins remain within blood vessels, light chains frequently escape and are excreted by the kidneys into urine, where they take the name of Bence Jones protein
.
It is also possible for paraproteins (usually whole immunoglobulins) to form polymer
s by aggregating with each other; this takes the name of macroglobulinemia
and may lead to further complications. For example, certain macroglobulins tend to precipitate within blood vessel with cold, a phenomenon known as cryoglobulinemia
. Others may make blood too viscous to flow smoothly (usually with IgM macroglobulins), a phenomenon known as Waldenström macroglobulinemia
.
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.
Monoclonal
Monoclonal cells are defined as a group of cells produced from a single ancestral cell by repeated cellular replication. Thus they can be said to form a single "clone". The process of replication can occur in vivo, or may be stimulated in vitro for laboratory manipulations...
gammaglobulin (in this case denominated "paraprotein") in the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
. It denotes an underlying immunoproliferative disorder.
It is sometimes considered equivalent to plasma cell dyscrasia.
Types
Paraproteinemias may be categorized according to the type of monoclonal protein found in blood:- Light chainLight chainA light chain is the small polypeptide subunit of a protein complex.More specifically, it can refer to:* Immunoglobulin light chain* Ferritin light chain* Myosin light chain* Kinesin light chain* Dynein light chainLight chain may also refer to:...
s only (also known as "AL amyloidosisAL amyloidosisAmyloid Light-chain amyloidosis, primary systemic amyloidosis or just primary amyloidosis is the most common form of systemic amyloidosis in the US. The disease is caused when a person's antibody-producing cells do not function properly and produce abnormal protein fibers made of components of...
or "light chain disease"). - Heavy chainHeavy chain]The immunoglobulin heavy chain is the large polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains. Several different types of heavy chain exist that define the class or isotype of an antibody. These heavy chain types vary...
s only (also known as "heavy chain diseaseHeavy chain diseaseHeavy chain disease is a form of paraproteinemia with a proliferation of cells producing immunoglobulin heavy chains.This disease is characterized by an excessive production of heavy chains that are short and truncated...
"); - Whole immunoglobulins (albeit often with an abnormal light / heavy chain ratio).
The three types of paraproteins may occur alone or in combination in a given individual. Note that while most heavy chains or whole immunoglobulins remain within blood vessels, light chains frequently escape and are excreted by the kidneys into urine, where they take the name of Bence Jones protein
Bence Jones protein
A Bence Jones protein is a monoclonal globulin protein found in the blood or urine, with a molecular weight of 22-24 kDa.Finding this protein is often suggestive of multiple myeloma or Waldenstrom's macroglobulinemia....
.
It is also possible for paraproteins (usually whole immunoglobulins) to form polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
s by aggregating with each other; this takes the name of macroglobulinemia
Macroglobulinemia
Macroglobulinemia is the presence of increased levels of macroglobulins in the circulating blood.A plasma cell dyscrasia resembling leukemia with cells of lymphocytic, plasmacytic, or intermediate morphology, which secrete an immunoglobulin M monoclonal component. There is diffuse infiltration of...
and may lead to further complications. For example, certain macroglobulins tend to precipitate within blood vessel with cold, a phenomenon known as cryoglobulinemia
Cryoglobulinemia
Cryoglobulinemia is a medical condition in which the blood contains large amounts of cryoglobulins - proteins that become insoluble at reduced temperatures. Cryoglobulins typically precipitate at temperatures below normal body temperature and will dissolve again if the blood is heated...
. Others may make blood too viscous to flow smoothly (usually with IgM macroglobulins), a phenomenon known as Waldenström macroglobulinemia
Waldenström macroglobulinemia
Waldenström's macroglobulinemia is cancer involving a subtype of white blood cells called lymphocytes. The main attributing antibody is Immunoglobulin M . WM is an "indolent lymphoma,"...
.
Possible causes
- LeukemiaLeukemiaLeukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
s and lymphomaLymphomaLymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
s of various types, but usually B-cell Non-Hodgkin lymphomaNon-Hodgkin lymphomaThe non-Hodgkin lymphomas are a diverse group of blood cancers that include any kind of lymphoma except Hodgkin's lymphomas. Types of NHL vary significantly in their severity, from indolent to very aggressive....
s with a plasma cell component.- Myeloma
- PlasmacytomaPlasmacytomaPlasmacytoma refers to a malignant plasma cell tumor growing within soft tissue or within the skeleton. The skeletal forms usually have other occult tumors and frequently disseminate to multiple myeloma over the course of 5–10 years. The soft tissue forms most often occur in the upper respiratory...
- Lymphoplasmacytic lymphoma
- Idiopathic (no discernible cause): some of these will be revealed as leukemias or lymphomas over the years.
- Monoclonal gammopathy of undetermined significanceMonoclonal gammopathy of undetermined significanceMonoclonal gammopathy of undetermined significance , formerly benign monoclonal gammopathy, is a condition in which a paraprotein is found in the blood during standard laboratory tests...
- Primary AL amyloidosisAmyloidosisIn medicine, amyloidosis refers to a variety of conditions whereby the body produces "bad proteins", denoted as amyloid proteins, which are abnormally deposited in organs and/or tissues and cause harm. A protein is described as being amyloid if, due to an alteration in its secondary structure, it...
(light chains only)
- Monoclonal gammopathy of undetermined significance
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
Albumin
Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...
and globulin
Globulin
Globulin is one of the three types of serum proteins, the others being albumin and fibrinogen. Some globulins are produced in the liver, while others are made by the immune system. The term globulin encompasses a heterogeneous group of proteins with typical high molecular weight, and both...
. 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 haptoglobinHaptoglobinHaptoglobin is a protein that in humans is encoded by the HP gene. In blood plasma, haptoglobin binds free hemoglobin released from erythrocytes with high affinity and thereby inhibits its oxidative activity. The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system...
, α2-macroglobulinMacroglobulinA macroglobulin is a plasma globulin of high molecular weight. Elevated levels of macroglobulins may cause manifestations of excess blood viscosity and/or precipitate within blood vessels when temperature drops .Other macroglobulins include alpha-2 macroglobulin, which is...
, α2-antiplasmin and ceruloplasminCeruloplasminCeruloplasmin is a ferroxidase enzyme that in humans is encoded by the CP gene.Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 1948...
.
- The β band consists of transferring, low-density lipoproteins, and complement systemComplement systemThe complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
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.
External links
- Paraproteinaemia at patient.co.uk.