Hepatitis C virus infection, cryoglobulinaemia, and beyond.
Hepatitis C virus (HCV) infection is the major cause of mixed cryoglobulinaemia (MC), an immune complex (IC)-mediated systemic vasculitis mainly involving the small blood vessels. The precise mechanism of cryoprotein production is currently unknown. HCV virions and non-enveloped core protein participate in the formation of cold-insoluble ICs. Cryoglobulinaemic patients represent a distinct HCV-infected population, in that significant HCV enrichment of lymphoid cells is accompanied by evidence of productive virus infection and increased frequency of B cells. Liver, the major target organ of HCV, is the site of accumulation of inflammatory infiltrates that shares many architectural features with lymphoid tissue and reflects a distorted homeostatic balance between factors that enhance cellular recruitment, proliferation and retention, and those that decrease cellularity (cell death and emigration). There is now overwhelming evidence of a direct contribution to B-cell growth and survival through production of a variety of cytokines and chemokines. Liver tissue over-expression and abnormal circulating levels of B-cell activating factor belonging to the TNF family can provide effective costimulatory mechanisms to sustain the B-cell clonal expansion, which constitutes molecular stigmata of MC. Indolent lymphoproliferation might act as the starting point of chronic, multistage lymphomagenesis. An innovative therapeutic strategy is directed to 'eradication of the virus' and deletion of B-cell clonalities.
Sansonno
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Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Italy. d.sansonno@dimo.uniba.it
Carbone
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De Re
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Dammacco
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D001402:B-Lymphocytes / Q000473:pathology; D049109:Cell Proliferation; D003449:Cryoglobulinemia / Q000628:therapy / Q000821:virology*; D003450:Cryoglobulins / Q000096:biosynthesis; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008221:Lymphoid Tissue / Q000821:virology; D016393:Lymphoma, B-Cell / Q000821:virology; D014657:Vasculitis / Q000821:virology
D003450:Cryoglobulins