title: Activation-induced cytidine deaminase in B cells of hepatits C virus-related cryoglobulinaemic vasculitis.
abstract: Immunoglobulin variable region heavy chain (IgVH ) somatic gene diversification is instrumental in the transformation process that characterizes hepatitis C virus (HCV)-related B cell lymphoproliferative disorders. However, the extent to which activation-induced cytidine deaminase (AID), an enzyme essential for IgV gene somatic hypermutation (SHM), is active in cryoglobulinaemic vasculitis (CV) remains unclear. AID mRNA expression in the peripheral blood of 102 chronically hepatitis C virus (HCV)-infected patients (58 with and 44 without CV) and 26 healthy subjects was investigated using real-time reverse transcription-polymerase chain reaction (RT-PCR). The features of activation-induced cytidine deaminase (AID) protein and mRNA transcripts were explored in liver tissue biopsies and portal tracts isolated using laser capture microdissection. In chronically HCV-infected patients, AID mRNA expression was almost threefold higher in those with than in those without CV and sevenfold higher than in healthy subjects (median-fold: 6.68 versus 2.54, P = 0.03 and versus 0.95, P = 0.0003). AID transcript levels were significantly higher in polyclonal than in clonally restricted B cell preparations in either CV or non-CV patients (median-fold, 15.0 versus 2.70, P = 0.009 and 3.46 versus 1.58, P = 0.02, respectively). AID gene expression was found to be related negatively to age and virological parameters. AID protein was found in portal tracts containing inflammatory cells that, in several instances, expressed AID mRNA transcripts. Our data indicate that the aberrant expression of AID may reflect continuous B cell activation and sustained survival signals in HCV-related CV patients.
authors.affiliation: Liver Unit, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Russi
authors.affiliation: Liver Unit, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Dammacco
authors.affiliation: Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia Medical School, Foggia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sansonno
authors.affiliation: Liver Unit, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pavone
authors.affiliation: Liver Unit, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Sansonno
mesh_terms: D000367:Age Factors; D000368:Aged; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D002470:Cell Survival / Q000276:immunology; D003449:Cryoglobulinemia / Q000150:complications / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D003564:Cytidine Deaminase / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000276:immunology; D014657:Vasculitis / Q000150:complications / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: HCV infection; cryoglobulinaemia; immunoglobulin variable gene; lymphoproliferation; somatic hypermutation