Serum Cryoglobulins

Clinical Significance

The term cryoglobulins refers to certain abnormal globulins, occasionally encountered in serum, that can precipitate or gel out when the serum is cooled to a low temperature, but that redissolve when the serum is rewarmed to 37 degree of Celcius. Cryoglobulins are not of hepatic origin, but are produced by some part of the reticulo-endothelial system. Often the presence of cryoglobulins is associated with increased levels of plasmacytes or cells resembling plasma cells in bone marrow. Some cryoglobulins are indistinguishable from true immune gamma globulins, whereas others present themselves as separate globulins migrating electrophoretically between the beta and gamma globulins. The molecular weight varies from 100,000 to 1,800,000, and the nitrogen content is of the order of 14 to 16 per cent.

The presence of cryoglobulins is associated with a number of different clinical conditions. They were first found associated with multiple myeloma, but are also encountered in kala-azar, lupus, lymphosarcoma, rheumatoid arthritis, and other autoimmune diseases, and are often associated with vascular sclerosis and platelet defects in blood coagulation. In essential cryoglobulinemia, the cryoglobulins are not associated with any well defined disease states. Clinically, cryoglobulinemia presents the features of Raynaud's syndrome-intolerance to cold, purpura, gangrene of the extremities, and skin sores. The cryoglobulins tend to gel out in the blood when it circulates in the toes and fingers, impairing circulation in these areas. Death may result from blockage of key blood vessels in such vital organs as the kidneys, brain, and lungs. The specific symptoms depend on the amount present and the degree of anti-inflammatory response of the body.

Cryoglobulins are soluble at body temperature (37 degree of Celcius). Occasionally, they will precipitate out at room temperature, but as a rule, sera have to be cooled to 10 degree of Celcius, or lower, before precipitation occurs. The temperature at which gelling will occur depends on the concentration and type of cryoglobulins present. The cryoglobulins in serum may separate out in the form of a gel or as a flocculent precipitate. Rewarming the serum to 37 degree of Celcius, will redissolve the floc or gel, but heating to 57 degree of Celcius, will destroy or modify the cryoglobulins so that they will no longer gel on cooling.