What is Cryoglobulin?

Also Known As: Cryocrit, Cryoprotein

Cryoglobulins are circulating proteins, specifically immunoglobulins (i.e., IgG, IgM, IgA, or light chains), that clump together (precipitate) when they are exposed to cold and dissolve when warmed. They may be present in small quantities in the blood of some healthy people but are most frequently associated with abnormal protein production and a variety of diseases and conditions. This test detects and measures the relative quantity of cryoglobulins in the blood.

Precipitated cryoglobulins can slow the flow of blood and block small blood vessels. The presence of large amounts of cryoglobulins in the blood, called cryoglobulinemia, can cause symptoms such as bruising, rashes, joint pain, weakness, and Raynaud phenomenon – pain, paleness, bluing, numbness, tingling, and coldness in the fingers and toes with exposure to cold. (These symptoms can also occur in people who do not have cryoglobulinemia.) Cryoglobulins can cause tissue damage that leads to skin ulcers and, in severe cases, to gangrene. They can activate the immune system, leading to the deposit of immune complexes in tissues, and cause inflammation, bleeding, and clotting that can affect circulation in organs such as the kidneys and liver.

There are three types of cryoglobulinemia:

• Type I, which consists of a monoclonal immunoglobulin – a single type of protein that is produced by an abnormal cloned cell. This type is often seen in people with myeloma or lymphoma.
• Type II, which consists of a mixture of monoclonal and polyclonal immunoglobulins. This type is often seen in people with hepatitis C or other viral infections.
• Type III, which consists of polyclonal immunoglobulins. This type is often seen in people with autoimmune diseases.

Initial testing does not distinguish between these three types of cryoglobulins, but the proteins involved can be determined through subsequent protein electrophoresis testing.

How is it used?

A cryoglobulins test is used to help detect the presence and relative quantity of cryoglobulins in the blood. It may be ordered along with other tests to help determine or rule out potential causes of cryoglobulinemia. The tests ordered depend on what condition or disease is suspected.

The sample is kept at or near body temperature during sample preparation. The person’s serum is then refrigerated for 72 hours and examined daily (up to 7 days) for precipitates. If there are any present, then the quantity is estimated and the sample is warmed to determine whether the precipitates dissolve. If they do, then cryoglobulins are present.

If the cryoglobulin test is positive, then it will be followed with protein electrophoresis and immunofixation electrophoresis (IFE) testing to determine which type(s) of protein are present as cryoglobulins and which type of cryoglobulinemia the person has.