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Immunochemical study of the cryoglobulins has produced a classification of three main types which present clinical correlates. With the current standard immunofixation technique the vast majority of cryoglobulins are presently classified as type II. High-resolution immunoelectrophoretic techniques (immunoblotting and two-dimensional polyacrylamide gel electrophoresis) have helped to identify new sub-types whose clinical relevance is as yet undetermined. Nevertheless, these sensitive techniques could contribute to elucidate the various stages in the natural history of HCV-related cryoglobulins, from possible earlier HCV-antigen-driven polyclonal B cell proliferation, to autonomous monoclonal benign, to malignant B cell proliferation.
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