Symposium on the Pathogenetic Mechanisms in Nephritis

Kidney International (1989) 35, 1004–1014; doi:10.1038/ki.1989.84

Renal involvement in essential mixed cryoglobulinemia

Giuseppe D'Amico1, G Colasanti1, F Ferrario1 and R A Sinico1

1Division of Nephrology, S. Carlo Borromeo Hospital, Milano, Italy

Correspondence: Professor Giuseppe D'Amico, Division of Nephrology, S. Carlo Hospital, Via Pio 11, No. 3, 20153 Milano, Italy.

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Abstract

Cryoglobulinemia is a pathological condition in hich the blood contains immunoglobulins that precipitate reversibly in the cold. According to the most idely used classification, based on the chemistry of the cryoglobulins involved, there are three types of cryoglobulinemia [1]. In type I cryoglobulinemia, the cryoprecipitable immunoglobulin is a single monoclonal immunoglobulin, usually a myeloma protein or a macroglobulin [2, 3]. Type II and III cryoglobulinemia are both mixed cryoglobulinemias, composed of at least to immunoglobulins. In both, a polyclonal IgG is bound to another immunoglobulin, hich is an antiglobulin, that is, it acts as an anti-IgG rheumatoid factor [4]. The important difference between these to types of mixed cryoglobulinemia is that in type II the antiglobulin component, which is usually of the IgM class, is monoclonal, while in type III it is polyclonal. As we will see later, this difference probably reflects different pathogenetic mechanisms: polyclonal anti-IgG immunoglobulins involved in type III cryoglobulinemia are derived from perturbation and magnification of the physiologic mechanism of production of antiglobulins concerned with immunoregulation and are probably antigen-driven, whereas the monoclonal anti-IgG immunoglobulins of type II-mixed cryoglobulinemia may be derived from the abnormal proliferation of a special clone of B lymphocytes, probably as a consequence of lymphoproliferative disorder [5].

In the last 20 years, cryoglobulinemia has been found in association with an increasing variety of diseases [1, 6]. Type I cryoglobulins are usually found in myelomas and Waldenstrom's macroglobulinemias. A great percentage of the mixed cryoglobulinemias, hich are 60 to 75% of all cryoglobulinemias [1, 7], are found in connective tissue diseases, in infectious or lymphoproliferative disorders, in hepatobiliary diseases or in immunologically-mediated glomerular diseases, and can therefore be considered "secondary mixed cryoglobulinemias". However, for approximately 30% of all mixed cryoglobulinemias the etiology is not clear and the cryoglobulinemia is referred to as "essential". The clinical syndrome of essential mixed cryoglobulinemia (EMC) as first described by Meltzer et al in 1966 [3]. It as characterized by purpura, weakness, arthralgia, and in some of the patients by glomerular lesions. Many subsequent reports have further defined this syndrome. They also indicate that the incidence of EMC varies in different geographical areas, the majority of cases having been reported in the Mediterranean countries, namely Italy, France, Spain and Israel [5,6]. They have confirmed that the syndrome can be associated with either type II or type III cryoglobulins. In the rheumatological surveys, patients with type III outnumbered those with type II EMC [3, 7–10]. On the contrary, surveys based on renal involvement indicated a large prevalence of type II EMC, the monoclonal IgM component being nearly always an IgMk [10–12].

While the glomerular lesions were variable and non-specific in the few cases of type III EMC with renal involvement, in type II EMC, in which IgMk as the monoclonal component, a particularly well characterized pattern of glomerular disease has been described.

We will consider to this special subgroup of patients with type II-EMC in this review , since we think that the description of their renal disease may shed light on the more general problem of the pathogenesis and mechanisms of glomerular and vascular damage in immunologically-mediated renal diseases.

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