Cryoglobulinemia
Encyclopedia
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 (37 degrees Celsius) and will dissolve again if the blood is heated. Cryoglobulinemia can be associated with various diseases such as multiple myeloma
and hepatitis C
infection.
such as multiple myeloma
or Waldenström macroglobulinemia
. Types II and III are strongly associated with infection by the hepatitis C virus
.
There are three different types of cryoglobulins that have been observed to form in the blood.
Types II and III have rheumatoid factor
(RF) activity and bind to polyclonal immunoglobulins. These two types are referred to as mixed cryoglobulinemia (MC). When the temperature is raised, the precipitated cryoglobulins will dissolve back into the serum.
In 2006 it was discovered that there are unusual cryoglobulins that show a microheterogeneous composition, with an immunochemical structure that cannot be fit into any of the classifications. A classification of a type II-III variant has been proposed because they are composed of oligoclonal IgMs with traces of polyclonal immunoglobulins
pneumonia
,post streptococcal glomerulonephritis, multiple myeloma
, certain leukemia
s, primary macroglobulinemia
, and some autoimmune disease
s, such as systemic lupus erythematosus
and rheumatoid arthritis
,. This is also found occasionally as a symptom
in 35% of chronic hepatitis C
infections.
It is important to note that these two different, yet highly representative, clinical syndromes generally reflect different types of underlying CG:
Multiple myeloma
Multiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
and hepatitis C
Hepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...
infection.
Classification
Cryoglobulinemia is classically grouped into three types according to the Brouet classification. Type I is most commonly encountered in patients with a plasma cell dyscrasiaLymphoproliferative disorders
Lymphoproliferative disorders refer to several conditions in which lymphocytes are produced in excessive quantities. They typically occur in patients who have compromised immune systems...
such as multiple myeloma
Multiple myeloma
Multiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
or 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,"...
. Types II and III are strongly associated with infection by the hepatitis C virus
Hepatitis C virus
Hepatitis C virus is a small , enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae...
.
There are three different types of cryoglobulins that have been observed to form in the blood.
| Type | Composition | Percent | Description |
|---|---|---|---|
| Type I | isolated monoclonal 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... immunoglobulins |
10-15% of the total cases | These are composed of a single monoclonal immunoglobulin paraprotein Paraprotein A paraprotein is an immunoglobulin or immunoglobulin light-chain that is produced in excess by the clonal proliferation of plasma cells. Detection of paraproteins in the urine or blood is most often associated with benign MGUS , where they remain "silent", and multiple myeloma. An excess in the... (usually IgM IGM IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium... ). Sometimes, these are represented by light chain Light chain A 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 and can be extracted from the urine, or they will accumulate in blood serum in the event of renal failure. |
| Type II | immunocomplexes formed by monoclonal 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... IgM |
50-60% of reported cases | They usually have a polyclonal component, usually IgG, and a monoclonal component, usually IgM, which has an RF function. The IgM can recognize intact IgG or either the Fab region or Fc region of IgG fragments. This is why most type II cryoglobulins are IgM-IgG complexes. |
| Type III | immunocomplexes formed by polyclonal IgM | 25-30% of the reported cases | These have very similar function to the type II cryoglobulins, however they are composed of polyclonal IgM and IgG molecules. |
Types II and III have rheumatoid factor
Rheumatoid factor
Rheumatoid factor is an autoantibody most relevant in rheumatoid arthritis. It is defined as an antibody against the Fc portion of IgG. RF and IgG join to form immune complexes that contribute to the disease process...
(RF) activity and bind to polyclonal immunoglobulins. These two types are referred to as mixed cryoglobulinemia (MC). When the temperature is raised, the precipitated cryoglobulins will dissolve back into the serum.
In 2006 it was discovered that there are unusual cryoglobulins that show a microheterogeneous composition, with an immunochemical structure that cannot be fit into any of the classifications. A classification of a type II-III variant has been proposed because they are composed of oligoclonal IgMs with traces of polyclonal immunoglobulins
Causes
These proteins may be present in mycoplasmaMycoplasma
Mycoplasma refers to a genus of bacteria that lack a cell wall. Without a cell wall, they are unaffected by many common antibiotics such as penicillin or other beta-lactam antibiotics that target cell wall synthesis. They can be parasitic or saprotrophic. Several species are pathogenic in humans,...
pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
,post streptococcal glomerulonephritis, multiple myeloma
Multiple myeloma
Multiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
, certain leukemia
Leukemia
Leukemia 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, primary 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 some autoimmune disease
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
s, such as systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
and rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
,. This is also found occasionally as a symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
in 35% of chronic hepatitis C
Hepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...
infections.
It is important to note that these two different, yet highly representative, clinical syndromes generally reflect different types of underlying CG:
- Hyperviscosity is typically associated with CG due to hematological malignancies and monoclonal immunoglobulins.
- "Meltzer's triad" (purpuraPurpuraPurpura is the appearance of red or purple discolorations on the skin that do not blanch on applying pressure. They are caused by bleeding underneath the skin...
, arthralgiaArthralgiaArthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
and myalgiaMyalgiaMyalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
) is generally seen with polyclonal CGs seen in essential-, viral-, or connective tissue diseaseConnective tissue diseaseA connective tissue disease is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs...
-associated CG.
External links
- Overview at Mayo ClinicMayo ClinicMayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...