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© Dirk Biddle
Cryoglobulins are primarily abnormal immunoglobulins that precipitate from blood serum in temperatures below 37 degrees C (98.6 degrees F) and redissolve on warming (other forms include cryofibrinogen and C-reactive protein-albumin complexes). Exposure of the face or hands, for example, of people with cryoglobulins can cause formation of precipitates that can block small blood vessels. Cryoglobulinaemia leads to systemic vasculitis because of a direct obstruction of the vessels, or to vascular inflammation induced by the deposition of IgG or IgM aggregate immune complexes within tissues which activate complement. Most frequently small arteries and veins are involved and typical symptoms include vascular purpura, arthralgia or arthritis, and myalgia. Purpura, with sometimes severe ulcerations of the legs, is described in almost 100% of patients. Other skin manifestations include urticaria and Raynaud's phenomenon, sometimes with acral necrosis. Arthralgia is frequent (70%) and arthritis is found in 35% of patients. Abdominal pain is seen in about 20% of patients and membranoproliferative glomerulonephritis (MPGN) occurs in around 10-30% of patients, often as a late and severe manifestation of the disease. Hypertension is seen in about 20% of patients and clinically relevant distal symmetric sensomotorical polyneuritis is frequent (20%) whereas the more dramatic acute mononeuritis (multiplex) or stroke are seen more rarely (1, 2).
Three main categories of cryoglobulins have been defined. These are: Type I, monoclonal immunoglobulin which self aggregate via their Fc receptors (usually IgG or IgM, infrequently IgA, rarely monoclonal light-chain protein); Type II, mixed cryoglobulins in which a monoclonal immunoglobulin is directed against a polyclonal immunoglobulin (usually monoclonal IgM, occasionally IgG or IgA complexed with autologous normal IgG), where the monoclonal IgM has rheumatoid factor activity; and Type III, mixed polyclonal immunoglobulin, none of which are homogenous (mixtures of polyclonal IgG and IgM), again with rheumatoid factor activity. However, the existence of cryoglobulins that do not fit well into any of the categories described above should be noted (2). Precipitation temperatures may vary, for example IgM cryoglobulins precipitate at lower temperatures that IgG cryoglobulins.
About 25% of cryoglobulinemias are type I, and 25% type II, while 50% are type III (3). Type I cryoglobulins may be associated with lymphoproliferative disorders including multiple myeloma, Waldenström's macroglobulinaemia, non-Hodgkin's lymphoma, and chronic lymphocytic leukaemia. The most frequent causes of Type II cryoglobulinaemia are chronic hepatitis C virus (HCV) infection, macroglobulinaemia, Sjögren's syndrome. Type III cryoglobulins are observed during many viral (including HCV), bacterial or parasitic infections, as well as in a series of autoimmune diseases such as Systematic lupus erythematosis, Polyarteritis nodosa, Rheumatoid arthritis, Scleroderma, Sjögren’s syndrome, and Henöch-Schonlein purpura, as well as in primary proliferative glomerulonephritis. There do remain a small number of cases that are idiopathic and these are considered as Essential cryoglobulinemia and associated with types II and III cryoglobulins.
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1. http://vasculitis.med.jhu.edu/typesof/cryoglobulinemia.html
2. (1998) Ann Rheum Dis., 57, 3-5.
3. http://www.aruplab.com/guides/clt/tests/clt_a178.jsp
Testing Information: http://www.aruplab.com/guides/clt/tests/clt_a178.jsp#1060127
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Cryoglobulin: Any of several proteins ( immunoglobulins ) similar to gamma-globulins (as in molecular weight) that precipitate - usually in the cold - from blood serum especially in pathological conditions (as multiple myeloma) and that redissolve on warming. (M+)
C-Reactive Protein: (CRP) This blood test is used as an indicator of acute inflammation. C-reactive protein is a protein of the pentraxin family, produced by the liver during periods of inflammation and detectable in serum in various disease conditions particularly during the acute phase of immune response. Normally C-reactive protein should be negative in the bloodstream. C-reactive protein is synthesised by hepatocytes and its production may be triggered by prostaglandin , E1, or pyrogen . It consists of five polypeptide sub units forming a molecule of total molecular weight 105 kD. It binds to polysaccharides present in a wide range of bacterial, fungal and other cell walls or cell surfaces and to lecithin and to phosphoryl or choline containing molecules. It is related in structure to Serum Amyloid and C polysaccharide. Conditions which can cause a positive C-reactive protein include: rheumatoid arthritis, lupus, pneumococcal pneumonia, rheumatic fever, cancer, tuberculosis and myocardial infarction .
Necrosis: The sum of the morphological changes indicative of cell death and caused by the progressive degradative action of enzymes, it may affect groups of cells or part of a structure or an organ. (OMD)
Death of living tissue; specifically: death of a portion of tissue differentially affected by local injury (as loss of blood supply, corrosion, burning, or the local lesion of a disease). (M+)
Hence 'necrotising'; the causing of tissue death.)
Monoclonal: Produced by, being, or composed of cells derived from a single cell ; especially - relating to or being an antibody derived from a single cell in large quantities for use against a specific antigen (as a cancer cell). (M+) Thus Monoclonal antibody therapy .