26:T453,

Neutralizing antibodies (NAb), a subset of antibodies against interferon-β (IFN-β) that inhibit activation of the IFN-β receptor, are presumed to bind to the receptor-binding site of IFN-β. The aim of this study was to identify specific epitopes for human NAb and nonneutralizing antibodies (NNAb) on the IFN-β molecule. Thirty-one 12-mer peptides and one 11-mer peptide representing the amino acid sequence of the human IFN-β molecule were used as antigens in an ELISA antibody assay. Significant antibody binding was observed at residues 1-12, 121-132, and 151-162. NNAb and NAb recognized residues 121-132 with equal frequency, but NAb had higher titers. NAb bound significantly more frequently to residues 1-12 and 151-162. There was a significant positive correlation between NAb titers and titers against residues 1-12. Binding to residues 1-12 was more pronounced in patients treated with IFN-β1a than in patients treated with IFN-β1b. Our results indicate a qualitative and quantitative difference between NAb and NNAb, with special emphasis on the recognition of different epitopes.

27:T4dc,

Interleukin-18 (IL-18), a unique cytokine that stimulates both T helper 1 (Th1) and Th2 responses, is associated with acute graft-versus-host disease (aGVHD), the major limiting toxicity following allogeneic stem cell transplantation. Here, we investigated the mechanism underlying the upregulation of IL-18 receptor (IL-18R) expression on T cells in murine aGVHD models. The induction of aGVHD elevated host serum IL-12 levels and increased expression of IL-18Rα chain (IL-18Rα) on engrafted T cells, in particular on CD8⁺ T cells. However, IL-18Rα expression did not increase on the CD4⁺ T cells of an IL-12-deficient host, indicating the IL-12-dependent upregulation of IL-18Rα expression on CD4⁺ T cells during aGVHD. Purified donor CD8⁺ T cells transferred in the host increased IL-18Rα expression. In vitro experiments showed that IL-18Rα expression upregulated on CD8⁺ T cells but not on CD4⁺ T cells on stimulation through the T cell receptor (TCR). These results suggest that IL-18Rα expression is differentially upregulated between CD4⁺ and CD8⁺ T cells during aGVHD, depending on endogenous IL-12 and TCR engagement, respectively.

28:T523,

We performed a pilot study to evaluate whether portal flow volume (PFV) changed in subjects with chronic hepatitis C virus (HCV) infection with respect to control patients after infusion of iloprost, a prostacyclin analog. Six subjects with chronic HCV infection and arteriopathy of the lower limbs (CHCVIA) and 4 control patients affected only by HCV infection (CHCV) were studied with color Doppler sonography. CHCVIA patients were examined before and after 3 days of iloprost infusion, and CHCV patients were examined before and after 3 days with no treatment. In each patient, PFV was obtained after calculating portal flow velocity (PV), portal diameter, and portal vein cross-sectional area. The mean difference between basal and final values of the PFV of CHCVIA patients was significant (p = 0.03), as was the difference in the PFV (final values expressed as percent of basal values) in CHCVIA patients compared with those obtained in the CHCV patients (p = 0.01). We have observed significant improvement in hepatic perfusion in CHCVIA patients compared with CHCV patients after iloprost infusion. In light of these results, we suggest some possible therapeutic implications in patients with HCV infection. Further studies are necessary to confirm this hypothesis.

29:T664,