Restricted isotypic antibody reactivity to hepatitis C virus synthetic peptides in immunocompromised patients.

An enzyme immunoassay based on three synthetic peptides from the core, NS4, and NS5 regions of hepatitis C virus allowed the detection of antibodies in 100% of immunocompetent infected patients and in 91% of immunocompromised patients (hemodialysis and hemophiliac patients). Immune impairment seemed to restrict the spectrum of antibody isotypes reacting to the core peptide.

High incidence of hepatitis C virus infection in hemodialysis patients in units with high prevalence.

The prevalence of hepatitis C virus (HCV) infection was evaluated in 227 hemodialysis patients from four units in Caracas, Venezuela, by using different second- and third-generation enzyme immunoassays (EIAs) and immunoblot assays. HCV antibodies were detected in 162 patients (71%) by the recombinant-based second-generation assays (Abbott and Ortho) and in 161 patients by the synthetic peptide-based EIA (UBI). Of the 162 HCV antibody-positive serum samples, 161 were confirmed to be positive by RIBA 3. HCV RNA was detected in 49 of 68 (72%) of the seropositive patients and in 5 of 21 (24%) of the seronegative ones. HCV RNA was not always correlated with an increase in alanine aminotransferase (ALT) levels. Among 20 patients positive for HCV RNA and for HCV antibodies (without any hepatitis B virus [HBV] marker), only 10 had elevated ALT levels. The possible interference of HBV for HCV replication was evaluated. No significant difference was found between the presence of HCV RNA and the presence of any HBV serological markers. The possible routes of transmission of HCV in hemodialysis patients are multiple, and some of them are still controversial. Of the HCV-positive patients, 30% received a blood transfusion, significantly more than the 15% found for the HCV-negative group. However, blood transfusions alone could not account for the high incidence observed in this group of patients (38% from 1994 to 1995). In conclusion, about one-quarter of the apparently non-HCV-infected patients were probably seroconverting, ALT may not be a useful indicator of HCV infection in hemodialysis patients, and nosocomial transmission of HCV may play a role in the spread of HCV in this group.

T cell hyperreactivity to IL-6 in chronic nonviremic HBV carriers despite normal IL-6 receptor or gp130 expression.

We previously showed that T cells from chronic nonviremic HBsAg carriers activated with immobilized OKT3 MAb are hyperreactive to monocyte accessory signals, mainly to interleukin-6 (IL-6). We have further characterized this T cell hyperreactivity using phytohemagglutinin (PHA) as the primary activating signal. PHA-stimulated T cells from nonviremic patients had a significantly higher response to addition of monocytes, monocyte supernatants, and IL-6 alone or combined with IL-1 beta when compared to controls. We examined if these effects could be mediated by a differential expression of IL-6 receptor (p80) or gp130 on resting or PHA-stimulated T cells. We found that PHA, IL-6, IL-1 beta, or IL-2 induced only small changes of the dull p80 expression on T cells. In contrast, we found a significant increase of gp130 expression on PHA-activated T cells compared to unstimulated T cells, which was down-regulated by the presence of IL-6. However, no significant differences in p80 or gp130 expression were detected between patients and controls within all the culture conditions tested. Our results confirm that IL-6 is involved in the in vitro T cell hyperreactivity of nonviremic HBV carriers and indicate that this effect is not mediated by disturbances of IL-6 receptor expression.

Anti-CD3-activated T cells from chronic nonviremic HBV carriers are hyperreactive to monocytic accessory signals.

We analyzed T cell responses through the CD3 activation pathway in a group of chronic HBV carriers. PBMC stimulated with the mAb OKT3 showed higher proliferative response in HBV-DNA(-) carriers compared to HBV-DNA(+) carriers and to controls. In contrast, no differences in proliferative responses were observed between HBV-DNA(-) carriers and controls in cell cultures stimulated with immobilized 64.1 mAb (SPB-64.1) which induces proliferation in the absence of monocytes. We further examined T cell responses in the presence of monocytes and their soluble factors to immobilized OKT3 mAb (SPB-OKT3). Purified T cells did not proliferate to SPB-OKT3. When autologous monocytes were added, higher proliferative response, IL-2 production, and IL-2 receptor expression were observed in HBV-DNA(-) carriers than in controls. An enhanced cell proliferation was also obtained when monocyte supernatants were added to T cells cultured with SPB-OKT3. Moreover, when IL-6 alone or combined with IL-1 was added to SPB-OKT3-stimulated T cell cultures, a significantly higher increase in T cell proliferation was detected in HBV-DNA(-) carriers. Our results thus show a T cell hyperreactivity to accessory signals from monocytes (mainly IL-6) in HBV-DNA(-) carriers, that is probably related to an ongoing viral clearance.