Hepatitis C virus RNA in plasma and blood mononuclear cells in patients with chronic hepatitis C treated with alpha-interferon.

Hepatitis C virus (HCV), a positive stranded RNA virus, is the main causative agent of post-transfusion and sporadic non-A non-B hepatitis worldwide. Paired samples of plasma and peripheral blood mononuclear cells (PBMC) from 11 patients with chronic hepatitis C treated with alpha-interferon (IFN) were tested, using a single step polymerase chain reaction (PCR), for the presence of HCV RNA. Before treatment, the viral genome was detected in all the plasma samples and 81.8% of PBMC. After 3 months of treatment, HCV RNA was still present in 63.6% of plasma samples but in only 27.3% of PBMC. A good correlation was observed between serum alanine aminotransferase level normalisation and disappearance of the viral genome in plasma. Among the six responder patients, five relapsed shortly after IFN withdrawal; HCV RNA became detectable again, especially in PBMC. These results show the presence of HCV in PBMC from most patients infected chronically. IFN therapy had an inhibitory effect on viral replication in lymphoid cells, but frequent relapses observed after cessation of treatment with IFN suggested persistence of HCV in these cells.

High prevalence of hepatitis C virus RNA in the supernatant and the cryoprecipitate of patients with essential and secondary type II mixed cryoglobulinemia.

Detection of hepatitis C virus RNA by polymerase chain reaction was performed in 26 patients with type II mixed cryoglobulinemia, and compared with anti-HCV antibody detection. The patients were divided into two groups according to etiology: 15 had essential type II mixed cryoglobulinemia and 11 had secondary type II mixed cryoglobulinemia. In the essential type II mixed cryoglobulinemia group, the prevalence of hepatitis C virus RNA detected by polymerase chain reaction was 60% in the supernatant and 93% in the cryoprecipitate. In the secondary type II mixed cryoglobulinemia group the prevalence of hepatitis C virus RNA was 45% in the supernatant and 55% in the cryoprecipitate. The differences between the two groups were not statistically significant. In both patient groups, detection of hepatitis C virus RNA in the cryoprecipitate was the most sensitive test for hepatitis C virus infection. These results suggest that hepatitis C virus might be involved in the origin of mixed cryoglobulinemia.

Characteristics of Epstein-Barr virus transformed B cell lines from patients with Alzheimer's disease and age-matched controls.

The characteristics of B cell lines isolated from patients with Alzheimer's disease (AD) and age-matched controls were investigated after having been transformed by Epstein-Barr virus (EBV). After isolation of mononuclear blood cells and in vivo or in vitro EBV infection, 35 and 21 lymphoblastoid cell lines (LCLs) were generated from 19 patients with AD (mean age 79.4 years) and 21 age-matched controls (mean age 80.0 years), respectively. B lymphocytes from AD patients were immortalised more easily than those from controls; the percentage of in vitro EBV infected LCLs (B95-LCLs) obtained in the AD group was significantly higher (76.2% versus 33.3% in the control group) and the mean time required for establishment was significantly lower (20.2 and 21.9 days versus 26.7 and 60.9 days in the control group). The EBV receptor and surface immunoglobulin (Ig) analyses showed no difference between the two groups. The expression of Epstein-Barr early antigens (EA) and viral capsid antigens (VCAs) revealed a tendency to higher viral replication in LCLs from AD patients; however, VCA expression remained limited to a small number of cells and did not affect overall cell growth. Finally, qualitative and quantitative differences were observed in the pattern of Ig production. Whereas spontaneously established LCLs from AD patients were generally monoclonal (80% of LCLs versus 33% in the control group), B95-LCLs were all polyclonal and secreted more IgM and IgA than those from controls; the mean IgM level was significantly higher in B95-LCLs from the AD group. These results suggest that B cells derived from AD patients seemed to be less differentiated than cells from age-matched controls.

Antibodies to viral antigens, xenoantigens, and autoantigens in Alzheimer's disease.

Sera from 19 patients with Alzheimer's disease (AD) and 21 control subjects were studied by immunofluorescence and enzyme immunoassay for antibody activity against various viruses and 12 self- and non-self-antigens. Total IgG mean level was significantly higher in the AD group; the IgG level was above 15 g/L in 52.8% of AD patients versus 14.3% of control subjects. Antiviral antibody titers showed no significant differences except for antibodies to herpes simplex virus-1, which were increased in control group. In contrast, autoantibodies were more frequently found in AD patients, and the prevalence of antibodies to spectrin, peroxidase, and thyroglobulin was significantly increased. Thus, in our series, autoimmune but not antiviral responses were heightened in at least 42% of AD patients (versus 9% of the control group) suggesting the existence of two subpopulations in the AD group.