, Volume 5, Issue 2, pp 115-121
Date: 03 Nov 2012

Mixed Cryoglobulinaemia

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Summary

Mixed cryoglobulins are cold-precipitable serum proteins composed of at least 2 immunoglobulins. One of the components is a polyclonal IgG while the other, usually of the IgM class, may be polyclonal or monoclonal and acts as an anti-IgG rheumatoid factor.

Mixed cryoglobulins are frequently detected in the serum of patients with infectious, immunological or lymphoproliferative disease; however, until recently, no identifiable disorder was found in 30 to 50% of all cryoglobulinaemic patients, their condition being defined as essential or idiopathic mixed cryoglobulinaemia. A large body of information is now accumulating in favour of the aetiological role of hepatitis C virus (HCV) in most of these patients. There is some evidence that HCV may enter lymphocytes and actively replicate in these cells. It is also conceivable that the presence of HCV in B lymphocytes may stimulate the production of anti-HCV antibodies which in turn, by binding together with HCV antigens and anti-IgG rheumatoid factors, form cryoprecipitable circulating immune complexes.

This important progress in the understanding of mixed cryoglobulinaemia has revolutionised the treatment of this disease. In fact, interferon-α has been proposed as first choice therapy, its beneficial effect being attributed to the antiviral activity of the drug. However, interferon therapy, at least with the standard dosages currently used in chronic hepatitis C, is initially effective in 60% or fewer of cases and the long term response is generally disappointing. Moreover, because of the late appearance of the beneficial effect and the frequent occurrence of adverse drug reactions, interferon-α cannot be recommended for the acute flare-ups of disease. In the event of an exacerbation, traditional immunosuppressive therapy, which may be associated with plasma-exchange, still has considerable efficacy.