Mixed cryoglobulinemia: a model of virus-related disease in internal medicine.
Like other hepatotropic viruses, hepatitis C virus (HCV) exhibits the property of inducing hepatocellular damage, possibly through induction of immune mechanisms that lead to hepatocellular necrosis. The early activated mechanisms include production of non-specific and specific antibodies, which represent the first line of defence against invading foreign pathogens. As a consequence, circulating immune complexes are promptly formed and antigen uptake and processing by specialized cells are enhanced. A major fraction of circulating immunoglobulins (Igs) are part of the spectrum of so-called "natural" antibodies, which include anti-idiotypic antibodies and molecules with rheumatoid factor (RF) activity. They mainly belong to the IgM class, are polyclonal and have no intrinsic pathogenetic potential. In 20-30% of HCV-infected patients, RFs share characteristics of high affinity molecules, are monoclonal in nature, and result in the production of cold-precipitating immune complexes and mixed cryoglobulinemia (MC). The persistent production of monoclonal RF molecules implies the existence of a further mechanism capable of restricting the reactivity and reflects a distinct selection of a cell population that can be maintained throughout life because it is continuously exposed to antigen pressure. Either polyclonal or monoclonal profiles of B-cell expansion are demonstrable in the liver of the majority of HCV-infected patients. The frequent detection of oligoclonal B cell expansion may, indeed, represent a key pathobiologic feature which sustains non-malignant B-cell lymphoproliferation. The preferential expansion of one clone would in turn lead to a monoclonal pattern, which could favor stochastic oncogenic events. Thus, it can be postulated that HCV is the stimulus not only for the apparent benign lymphoproliferative process underlying a wide spectrum of clinical features, but also for the progression to frank lymphoid malignancy in a subgroup of patients.
Dammacco
Franco
F
Department of Biomedical Seiences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical Sehool, Bari, Italy. f.dammacco@dimo.uniba.it
Lauletta
Gianfranco
G
Montrone
Michele
M
Sansonno
Domenico
D
D003449:Cryoglobulinemia / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D008954:Models, Biological