Biologic and clinical significance of cryoglobulins

Abstract

Eighty-six patients with cryoglobulinemia repeatedly underwent complete immunochemical and clinical evaluation during the course of their disease. Immunochemical analysis of the purified cryoglobulins allowed us to classify them into three groups. Type I cryoglobulins are made of isolated monoclonal immunoglobulin: IgM (11 cases), IgG (7 cases), IgA (2 cases) or Bence Jones protein (1 case). Type II cryoglobulins are mixed cryoglobulins with a monoclonal component possessing antibody activity towards polyclonal IgG. These cryoglobulins were mainly IgM-IgG (19 cases), sometimes IgG-IgG (2 cases) or IgA-IgG (1 case). Type III cryoglobulins (43 cases) are mixed polyclonal cryoglobulins, i.e., composed of one or more classes of polyclonal immunoglobulins and sometimes nonimmunoglobulin molecules such as beta₁C or lipoprotein. Most of these type III cryoglobulins are also immunoglobulin-anti-immunoglobulin immune complexes. This classification enabled us to establish correlations between the biologic findings and the clinical features as well as the underlying diseases. Cutaneous and vasomotor symptoms were most severe in patients with type I and II cryoglobulins. The usual clinical picture in patients with type II or III cryoglobulins consisted of chronic vascular purpura and mild Raynaud's phenomenon. Renal and neurologic involvement were more frequent in patients with type II and III cryoglobulins, and were of major prognostic significance. In our series, immunoproliferative and autoimmune disorders were the most frequent diseases associated with cryoglobulinemia. The former were associated with type I or II cryoglobulins and the latter mainly with type III cryoglobulins. Of note is that idiopathic cryoglobulinemia accounted for nearly 30 per cent of the cases despite repeated careful clinical evaluation and a mean follow up of 9 years. In 10 per cent of the cases, acute and severe symptoms necessitated emergency treatment with plasmapheresis and chemotherapy which allowed a satisfactory initial remission in all but one patient. Conversely, no treatment was definitively effective in patients with chronic symptoms such as vascular purpura.