Le crioglobuline miste: epidemiologia, clinica ed eziopatogenesi. Contributo personale.

The study of cryoglobulinemic syndromes carried out over the years by our research group has been wide-ranging and includes:1 immunochemical characterisation of the cryoimmunoglobulin, 2) histological and immunoistochemical study of bone marrow, 3) role of HCV, 4) HCv, cryoglobuinaemia and monoclonal gammopathies, 5) HCV, mixed cryoglobulinemia and lymphoprolifaration, 6) natural history and epidemiology of type II mixed cryoglobulinaemia, 7) followup of patients with cryoglobulinemic syndrome.Our most important achievements have been in the demostration of the monoclonal nature of symptomatic tipeII mixed cryoglobulinemia (igMk-IgG) associated with medullary aspects of nodular clonal B expansion. The subsequent report ( at the beginning of the 90s) of anti-HCV antibodies in the course of essential mixed cryoglobulinemia (EMC) was confirmed by us on a target population of 180 patients enlisted with the help of various medical and specialist department of Modena Policlinic and of hospitals in the Modena area. Accordingly we postulated a possible aetiopathogenetic role of the virus with respect to the aspects of clonal expansion. At the same time our case studies of patients qith monoclonal gammopathies, without cryoglobulinemic activity failed to reveal any connenction with HCV infection. Our findings qhich were followed up over a period of time by clinical, laboratory and instrumental checks, enabled us to show that nodular clonal B expansion, present in 75% of the HCV -correlated MCII cases, remains unchanged over time and that clinical manifestations of lymphoma do not appear; death in these cases is due mainly to vasculitis and/or infectious process. In conclusion, therefore HCV-correlated MCII must be seen as an autoimmune systemic disease of infectious origin in which bone-marrow complications are an expression of chronic viral stimulation.