Association of T regulatory cells with natural course and response to treatment with interferon-α in patients with chronic hepatitis B infection / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Regulatory T cell populations, particularly CD4(+)CD25(+) T regulatory cells, have been implicated in the persistence of hepatitis B virus (HBV) infection. However, no clear relationship has been established between the frequency of CD4(+)CD25(+) T regulatory cells in the peripheral blood and either the disease phases in the natural history of chronic HBV infection or in the response to interferon-α therapy.</p><p><b>METHODS</b>In the present study, three different common markers of CD4(+)CD25(+) T regulatory cells were used to determine the numbers of T regulatory cells in healthy controls and in patients with chronic HBV infection.</p><p><b>RESULTS</b>No significant difference was found when samples were gated for CD25(hi) and CD25(+)FoxP3(+) T cells. A significant correlation was found between the number of CD4(+) Treg cells that gated with CD25(+)FoxP3(+) and CD25(+)CD127(low/-) in healthy controls and in patients with chronic hepatitis B (CHB) (r = 0.67, 0.59; P < 0.01). The percentages of Treg cells were (8.56 ± 2.01)% in asymptomatic carriers (Asc), (8.74 ± 3.04)% in inactive HBsAg carriers, (10.7 ± 2.93)% in CHB and (7.42 ± 1.28)% in healthy controls (F = 11.1, P < 0.001). The percentage of Treg cells in patients with CHB was higher than in asymptomatic HBV patients, inactive HBsAg carriers, or healthy controls (P < 0.01). The proportion of CD4(+)CD25(+)CD127(low/-) T cells in patients who responded to interferon-α was (11.9 ± 3.3)%, (9.1 ± 2.4)% and (9.0 ± 2.9)% at baseline, week 12 and week 24 after treatment, respectively (Z = 2.42, P < 0.05; Z = 2.67, P < 0.01).</p><p><b>CONCLUSIONS</b>These results suggest that the proportion of the CD4(+)CD25(+) regulatory T cells might be affected by the application of different markers in process to detect T regulatory cells. The frequency of Treg cells was increased in patients with CHB, which might be associated with the disease activity of these patients and contribute to prevention of extensive liver damage. A decline in Treg cells at week 12 of treatment might be associated with a better response to treatment with interferon-α.</p>

Preliminary identification and analysis of point mutations correlated with response to interferon-alpha in hepatitis B virus post-transcriptional regulatory elements / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is still unclear whether viral genetic variability influences response to interferon (IFN)-alpha treatment. Recent reports suggest that IFN-alpha effects may be associated with hepatitis B virus (HBV) post-transcriptional regulation. This study was designed to explore the heterogeneity of HBV post-transcriptional regulatory elements (HPRE) and the relationship between the diversity of HPRE and the response to IFN-alpha treatment.</p><p><b>METHODS</b>The HPRE sequences from 31 Chinese patients infected with HBV were determined by directly sequencing of polymerase chain reaction (PCR) product, and comparing them to those from Caucasian patients. Subsequently, eukaryotic expression vectors containing HPRE at various points were constructed and transfected into HepG2 cells, which were then exposed to recombinant human cytokines.</p><p><b>RESULTS</b>The T to C point mutation at nt 1504 and the C to T (G) at nt 1508 in HPRE were found in 21 and 19 patients with chronic hepatitis B, respectively; the C to T point mutation at nt 1509 was found in 17 patients. These point mutations did not exist in the HPRE of the Caucasian patients. The activity of the CAT gene obviously increased in the case of T to C point mutation at nt 1504, but did not change in the case of the C to T (G) mutations at nt 1508 and 1509. The activity of the CAT gene at these point mutations of HPRE could be inhibited by IFN-alpha/gamma and tumor necrosis factor (TNF)-alpha except for the point mutations at nt 1508 of HPRE which may escape the suppression role of IFN-alpha on HPRE.</p><p><b>CONCLUSIONS</b>There are point mutations between the HPRE of Chinese and Caucasian HBV patients, which might be correlated with response to IFN-alpha. The variation of HPRE might affect the function of HPRE and influence the regulative function of IFN-alpha other than that of IFN-gamma or TNF-alpha on HPRE.</p>