Cryoglobulins

Abstract

Serum cryoglobulins are found in a wide spectrum of disorders but are often transient and without clinical implications. Monoclonal cryoglobulins are usually associated with haematological disorders, whereas mixed cryoglobulins are found in many infectious and systemic disorders. So called essential mixed cryoglobulinaemia shows a striking association with hepatitis C virus (HCV) infection (> 90%). It is a systemic vasculitis (leucocytoclastic vasculitis) with cutaneous and multiple visceral organ involvement. Chronic HCV infection can lead to a constellation of autoimmune and neoplastic disorders. In this review, the aetiology, diagnosis, disease heterogeneity, and treatment of cryoglobulinaemia are discussed.

Mixed cryoglobulinemia

“…This particular serological subset, termed type II-III mixed cryoglobulinemia (MC), could represent an intermediate, evolutive state from type III to type II MC. Moreover, type II-III MC could fit together the most recent molecular studies showing the presence of oligoclonal B-lymphocyte proliferation in the liver and bone marrow biopsies from MC patients [3]. In two third of type II MC, a cross-idiotype WA monoclonal RF (firstly isolated from the serum of a patient with Waldenström's macroglobulinemia) has been demonstrated [14].…”

“…This is an in vitro phenomenon ( Fig. 1), the actual mechanism(s) of cryoprecipitation remains obscure, it could be secondary to intrinsic characteristics of both mono-and polyclonal immunoglobulin (Ig) components, it can be caused as well by the interaction among single components of the cryoprecipitate [1][2][3][4][5][6][7][8][9][10][11][12][13][14].…”

“…Both type II and type III mixed cryoglobulins are immune complexes composed of polyclonal IgGs, the autoantigens, and mono-or polyclonal IgMs, respectively; the IgMs are the corresponding autoantibodies with rheumatoid factor (RF) activity [3][4][5][6]. With more sensitive methodologies, i.e.…”

“…With more sensitive methodologies, i.e. immunoblotting or 2-dimensional polyacrylamide gel electrophoresis, type II mixed cryoglobulins frequently shows a microheterogeneous composition; in particular, oligoclonal IgM or a mixture of polyclonal and monoclonal IgM can be detected [3]. This particular serological subset, termed type II-III mixed cryoglobulinemia (MC), could represent an intermediate, evolutive state from type III to type II MC.…”

“…Type I cryoglobulinemia is almost invariably associated with well-known hematological disorders and is frequently asymptomatic per se; similarly, circulating mixed cryoglobulins are commonly detected in a great number of infectious or systemic disorders [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. On the contrary, 'essential' MC represents a distinct disorder [3][4][5][6], which can be classified among systemic vasculitides [3][4][5][6][7][8][9][10].…”