A myeloma protein is an abnormal

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and Viral disease, viruses. The antibody recognizes a unique m ...

(immunoglobulin) or (more often) a fragment thereof, such as an

immunoglobulin light chain ] The immunoglobulin light chain is the small Peptide, polypeptide subunit of an antibody (immunoglobulin). A typical antibody is composed of two immunoglobulin (Ig) heavy chains and two Ig light chains. In humans There are two types of light ...

, that is produced in excess by an abnormal

monoclonal Monoclonality refers to the state of a line of cells that have been derived from a single clonal origin. Thus "monoclonal cells" can be said to form a single clone. The term ''monoclonal'' comes from the Ancient Greek ''monos'', meaning "alone" o ...

proliferation of

plasma cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B lymphocytes and secrete large quantities of proteins called antibodies in response to being presented specific sub ...

s, typically in

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, ane ...

Monoclonal gammopathy of undetermined significance Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia in which plasma cells or other types of antibody-producing cells secrete a myeloma protein, i.e. an abnormal antibody, into the blood; this abnormal protein i ...

. Other terms for such a protein are monoclonal protein, M protein, M component, M spike, spike protein, or paraprotein. This proliferation of the myeloma protein has several deleterious effects on the body, including impaired immune function, abnormally high blood viscosity ("thickness" of the blood), and kidney damage.

History

The concept and the term ''paraprotein'' were introduced by the

Berlin Berlin is Capital of Germany, the capital and largest city of Germany, both by area and List of cities in Germany by population, by population. Its more than 3.85 million inhabitants make it the European Union's List of cities in the European U ...

pathologist Dr Kurt Apitz in 1940, then the senior physician of the pathological institute at the

Charité The Charité – Universitätsmedizin Berlin (Charité – Berlin University of Medicine) is one of Europe's largest university hospitals, affiliated with Humboldt University and Free University Berlin. With numerous Collaborative Research Ce ...

hospital. Paraproteins allowed the detailed study of immunoglobulins, which eventually led to the production of

monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ...

in 1975.

Cause

Myeloma is a

malignancy Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

of plasma cells. Plasma cells produce immunoglobulins, which are commonly called antibodies. There are thousands of different antibodies, each consisting of pairs of heavy and light chains. Antibodies are typically grouped into five types: IgA, IgD, IgE, IgG, and IgM. When someone has myeloma, a malignant clone, a rogue plasma cell, reproduces in an uncontrolled fashion, resulting in overproduction of the specific antibody the original cell was generated to produce. Each type of antibody has a different number of light chain and heavy chain pairs. As a result, there is a characteristic normal distribution of these antibodies in the blood by molecular weight. When there is a malignant clone, there is usually overproduction of a single antibody, resulting in a "spike" on the normal distribution (sharp peak on the graph), which is called an M spike (or monoclonal spike). People will sometimes develop a condition called MGUS (

), where there is overproduction of one antibody but the condition is benign (non-cancerous). An explanation of the difference between multiple myeloma and MGUS can be found in the International Myeloma Foundation's Patient Handbook. and Concise Review Detection of paraproteins in the

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in th ...

is most often associated with benign

monoclonal gammopathy of undetermined significance Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia in which plasma cells or other types of antibody-producing cells secrete a myeloma protein, i.e. an abnormal antibody, into the blood; this abnormal protein i ...

(MGUS), where they remain "silent", and

. An excess in the blood is known as

paraproteinemia Monoclonal gammopathy, also known as paraproteinemia, is the presence of excessive amounts of myeloma protein or monoclonal gamma globulin in the blood. It is usually due to an underlying immunoproliferative disorder or hematologic neoplasms, esp ...

. Paraproteins form a narrow band, or 'spike' in

protein electrophoresis Protein electrophoresis is a method for analysing the proteins in a fluid or an extract. The electrophoresis may be performed with a small volume of sample in a number of alternative ways with or without a supporting medium: SDS polyacrylamide gel ...

as they are all exactly the same protein. Unlike normal immunoglobulin antibodies, paraproteins cannot fight infection.

Serum free light-chain measurement Immunoglobulin light chains that are circulatory system, circulating in serum in a free (unbound) state are called free light chains (FLCs). Measurement of the serum level of FLCs became practical as a clinical blood test in recent decades. Thes ...

can detect free light chains in the blood. Monoclonal free light chains in the serum or urine are called

Bence Jones protein Bence Jones protein is a monoclonal globulin protein or immunoglobulin light chain found in the urine, with a molecular weight of 22–24 kDa. Detection of Bence Jones protein may be suggestive of multiple myeloma or Waldenström's macroglobu ...

Interpretation upon detection

Blood serum Serum () is the fluid and solute component of blood which does not play a role in clotting. It may be defined as blood plasma without the clotting factors, or as blood with all cells and clotting factors removed. Serum includes all proteins not ...

paraprotein levels of more than 30 g/L is diagnostic of

smouldering myeloma Smouldering myeloma is a disease classified as intermediate in a spectrum of step-wise progressive diseases termed plasma cell dyscrasias. In this spectrum of diseases, a clone of plasma cells secreting monoclonal paraprotein (also termed myeloma ...

, an intermediate in a spectrum of step-wise progressive diseases termed

plasma cell dyscrasia Plasma cell dyscrasias (also termed plasma cell disorders and plasma cell proliferative diseases) are a spectrum of progressively more severe monoclonal gammopathies in which a clone or multiple clones of pre-malignant or malignant plasma cells (s ...

s. Elevated paraprotein level (above 30 g/L) in conjunction with end organ damage (elevated calcium,

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

, anemia, or bone lesions) or other biomarkers of malignancy, is diagnostic of

, according to the diagnostic criteria of the

International Myeloma Working Group The International Myeloma Foundation (IMF) is an American non-profit organization serving patients with myeloma, a cancer of plasma cells in the bone marrow. The IMF also provides support and information for family members, caregivers of myeloma ...

, which were updated in 2014. Detection of paraprotein in serum of less than 30 g/L is classified as

in cases where clonal plasma cells constitute less than 10% on bone marrow biopsy and there is no myeloma-related organ or tissue impairment.

References

External links

* {{MeshName, Paraproteins
Educational Resource for Paraproteins

Hematology Immune system Oncology Proteins

History

Cause

Interpretation upon detection

See also

References

External links