Definition
- Cryoglobulins are abnormal serum proteins that precipitate at low temperatures and dissolve when temperature is raised. They cannot be identified by serum protein electrophoresis. Cryoglobulins are made up of monoclonal antibodies IgM or IgG, rarely IgA. IgM tends to precipitate at lower temperatures than does IgG cryoglobulin.
- Other names: cryocrit, cryoprotein.
- Cryoglobulins are classified as follows:
- Type I (monoclonal immunoglobulin, especially IgM Ž º type)
- Causes 25% of cases.
- Most commonly associated with multiple myeloma and Waldenstr ƒ ¶m macroglobulinemia; other lymphoproliferative diseases with M components; occasionally it may be idiopathic.
- If present in large amounts (>5 mg/dL serum), blood may gel when drawn.
- Severe symptoms (e.g., Raynaud syndrome, gangrene without other causes).
- Type II (monoclonal immunoglobulin mixed with at least one other type of polyclonal immunoglobulin, most commonly IgM and polyclonal IgG; always with RF)
- Causes up to 25% of cases
- Associated most often with chronic hepatitis C virus (HCV) infection; less often with hepatitis B virus (HBV), EBV, bacterial and parasitic infections, autoimmune disorders, Sj ƒ ¶gren syndrome, syndrome of essential mixed cryoglobulinemia, immune complex nephritis (e.g., membranoproliferative GN, vasculitis)
- High titer RF without definite rheumatic disease
- C4 levels decreased
- Type III (mixed polyclonal immunoglobulin, most commonly IgM " “IgG combinations, usually with RF)
- Causes approximately 50% of cases
- Most commonly associated with lymphoproliferative disorders, connective tissue diseases (e.g., SLE), and persistent infections (e.g., HCV)
- Normal range:
- Usually present in small amounts (<1 mg/dL serum) in normal persons.
- If positive, immunotyping of the cryoprecipitate is performed.
Use
- To assist in diagnosis of neoplastic diseases, acute and chronic infections, and collagen diseases
- To detect cryoglobulinemia in patients with symptoms indicating or mimicking Raynaud disease, cyanosis, and skin ulceration
- To monitor course of connective tissue disorders
Interpretation
- Cryoglobulins with a detected monoclonal protein normally prompt a clinical investigation to determine if an underlying disease exists.
Limitations
- Cryoglobulins are not to be confused with cryofibrinogen (see above section), which precipitates only in plasma, under cold conditions.
- Failure to maintain sample at normal body temperature before centrifugation can affect results.
- A recent fatty meal can increase turbidity of the blood.
Suggested Readings
1Coblyn ‚ JS, McCluskey ‚ RT. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 3-2003: a 36-year-old man with renal failure, hypertension and neurologic abnormalities. N Engl J Med. 2003;348:333 " “342. 2Kallemuchikkal ‚ U, Gorevic ‚ PD. Evaluation of cryoglobulins. Arch Pathol Lab Med. 1999;123: 119 " “125.