Cryoglobulins and pyroglobulins: an overview

Cryoglobulins are serum proteins with heterogeneous etiopathogenetic and immunochemical properties. What they have in common is temperature-dependent insolubility, in that at temperatures below 37 degrees C (often around 4 degrees C) they precipitate, and then redissolve at 37 degrees C. When the etiopathogenesis of the cryoglobulinemia is unknown, which is true for many patients, the condition is called idiopathic or essential cryoglobulinemia, whereas it is termed secondary whenever it appears to be associated with one of several diseases. Cryoglobulinemia has indeed been found in patients with lymphoproliferative and autoimmune disorders, liver diseases, infectious (viral, bacterial, fungal and parasitic) diseases, and so on. Cryoglobulins are usually classified according to their immunochemical properties as single-type monoclonal, mixtures of a monoclonal Ig with non-immunoglobulin material (DNA, lipoprotein, complement), mixed with one monoclonal Ig or mixed polyclonal, in which constitutive Ig fractions are polyclonal. As compared with normal Ig, cryoimmunoglobulins have sometimes been found to exhibit a peculiar amino acid structure of their heavy chains, less often of their light chains as well, and to have a lower carbohydrate content. Such structural abnormalities may contribute to their loss of solubility at low temperatures, possibly associated to the steric changes induced by the low temperature, causing the precipitate to form. The most common clinical features of cryoglobulins are correlated with vasculitis in the various organs and sometimes with increased viscosity of the plasma. Signs and symptoms include purpura, ulcers of the extremities, arthralgia, proteinuria, hepatic damage, abdominal pain, congestive heart failure, mental confusion, oligo-anuria, hemorrhagic diathesis, and coma. Pyroglobulins are also serum proteins with temperature-dependent insolubility. However, although they precipitate out of serum heated at 56 degrees C for half an hour, they do not resolubilize when the serum is returned to 37 degrees C. Pyroglobulins have been mainly found in patients with lymphoproliferative diseases (especially Waldenström's macroglobulinemia, with or without cryoglobulinemia), systemic lupus erythematosus, and neoplasia. So far, only single monoclonal IgG, IgM or IgA pyroglobulins have been described. Since they precipitate only at 56 degrees C, pyroglobulins do not cause clinical symptoms and they are usually discovered by chance.