Electrophoresis

IMMUNOFIXATION [IMMUNOELECTROPHORESIS] Immunoglobulin qunntiotion for monrtofing

Figure 3 The laboratory investigation of cryoglobulin.

in the absence of obvious underlying disease, the diagnosis of 'essential cryoglobulinemia' must be kept under continuous review as it is very likely to represent 1) the preclinical stage of a lymphoprolifer-ative disease; 2) the only sign of an underlying infection or chronic inflammatory disease; 3) the preclinical stage of cirrhosis or chronic active hepatitis.

To detect cryoglobulins, blood samples should be sent to the laboratory warm and separated at 37°C. The investigative procedure is summarized in Figure 3. The precipitate does not always redissolve easily, probably due to intermolecular disulfide bond formation. Electrophoresis of the warmed serum and the redissolved precipitate reveals a monoclonal component in about 60% of cases (type I or type II). In type II cases this is most often IgM k but confusion may arise as the monoclonal band seen on electrophoresis may be found to contain IgM, IgG, k and X on immunofixation or immunoelectrophor-resis owing to the presence of bound polyclonal IgG.

The analysis of cryoprecipitates in trace amounts using two-dimensional Polyacrylamide gel electrophoresis, has shown that polyclonal IgG are associated with a mixture of polyclonal and monoclonal IgM. These cryoglobulins have been tentatively named type IT—TIT cryoglobulins. They are theoretically relevant since they may represent the transition from type III (mixed-polyclonal) to type II (mixed-monoclonal) cryoglobulins. This transformation could be induced by the chronic antigen stimulation caused by persistent HCV infection documented in most patients with 'essential' mixed cryoglobulinemia.

Patients with cryoglobulins containing a monoclonal component should be investigated for an underlying lymphoproliferative disease and the presence of hypogammaglobulinemia and/or Bence Jones proteins are useful indicators.

Mixed cryoglobulins frequently have anticomplementary activity and low serum complement levels, especially of C4, may be seen.

Immunohistological studies of skin lesions in cryoglobulinemia show IgM, IgG and/or C4 in the blood vessel walls.

See also: Bence Jones proteins; Idiotype; Immune complexes; Immunoelectrophoresis; Lymphoma; Plasmapheresis; Rheumatological disorders; Sjögrens syndrome; Systemic lupus erythematosus (SLE), human.

Further reading

Agnello V, Chung RT and Kaplan LM (1992) A role for hepatitis C virus infection in type II cryoglobulinemia. New England Journal of Medicine 327: 1490-1495. Brouet J-C, Clauvel J-P, Danon F, Klein M and Seligmann M (1974) Biological and clinical significance of cryoglobulins. American Journal of Medicine 57: 775-788. Cacoub P, Fabiani FL, Musset L et al (1994) Mixed cryoglobulinemia and hepatitis C virus. American Journal of Medicine 96: 124-132. Dammacco F, Miglietta A, Lobreglio G and Bonomo L (1986) Cryoglobulins and pyroglobulins: an overview. La Ricerca in Clinica e in Laboratorio 16: 247-267. Denman AM (1992) Cryoglobulins and the immunopatho-logical manifestations of autoimmune disease. Clinical and Experimental Immunology 87: 169-171. Monti G, Galli M, Invernizzi F et al and the CISC (1995) Cryoglobulinemias: a multi-centrc study of the early clinical and laboratory manifestations of primary and secondary disease. Quarterly Journal of Medicine 88: 115-126.

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