CRYOGLOBULINS

CLINICAL UTILITY:

Cryoglobulins are immune complexes or aggregates of immunoglobulins which precipitate upon cold exposure. They fall into three categories: Type I: monoclonal cryoglobulins; Type II: mixed monoclonal-polyclonal cryoglobulins, and Type III: mixed polyclonal cryoglobulins.

Type I cryoglobulins are monoclonal IgG, IgM, IgA or Bence Jones protein, and occur in the sera of patients with Waldenstrom’s macroglobulinemia, lymphoma or multiple myeloma. This type comprises 20-25% of all cryoglobulins, and when present, generally is found in high serum concentration (cryocrit >3%).

Type II cryoglobulins, a mixed type which consists of a monoclonal IgG, IgM or IgA with antibody activity against a polyclonal IgG, often are associated with lymphoproliferative diseases such as Waldenstrom’s macroglobulinemia, lymphoma, myelomas and other tumors, and with rheumatoid diseases, other autoimmune disorders and a number of acute and chronic infectious states. In essential mixed cryoglobulinemia, features include cutaneous vasculitis, glomerulonephritis, arthritis and neuropathy. This syndrome sometimes develops as a consequence of hepatitis B infection. The serum level of Type II complexes is usually moderate to high (>1%). Complexes of polyclonal immunoglobulins (Type III cryoglobulins) sometimes are associated with rheumatoid arthritis, Sjogren’s syndrome, SLE, infectious mononucleosis, glomerulonephritis, and a variety of other rheumatoid diseases and chronic infections.

Approximately 50% of all cryoglobulins are Type III, and usually occur in the serum in low concentration (< 1%). Tests available in our lab include the cryoglobulin screen (for presence of cryoglobulin), and the cryoglobulin identification, in which the class of immunoglobulin and clonality of the cryoglobulin are determined.

METHOD DESCRIPTION:

Cryoglobulin (Screen): Serum (see specimen requirement for handling) is refrigerated for two days to allow the precipitate to form, then centrifuged and measured for percent of precipitate present. The tube is then placed in a 37°C water bath. The precipitate must redissolve, at least partially, to be reported as a cryoglobulin. If no precipitate is present, the result is reported as "negative". Quantitation is based on the percentage of the total serum volume containing the centrifuged cryoglobulin (cryocrit).

Cryoglobulin Identification: Following the procedure above, the precipitate is washed in ice-cold saline to free the cryoglobulin from other serum proteins. The washed cryoglobulin is then suspended in saline, warmed to 37°C and tested by immunofixation to determine the class and clonality of the immunoglobulin. If a monoclonal component is present, the class of immunoglobulin is identified. If the cryoglobulin is polyclonal, the result is reported as “No monoclonal component present”.

REFERENCE RANGE:

Negative.

SPECIMEN REQUIREMENTS:

Screen: At least 5 ml serum obtained from 15-20 ml of blood drawn and alowed to clot in a red top tube at 37°C. Do not freeze.
Identification: Send at least 10 ml serum handled as above.