The association between the genetic polymorphism of HLA-DQA1, DQB1, and DRB1 and serum alanine aminotransferase levels in chronic hepatitis C in the Chinese population.

BACKGROUND AND AIM: To investigate a possible association between HLA genes with serum alanine aminotransferase (ALT) levels and evaluate whether the HLA-DQA1, DQB1, and DRB1 genes could influence the development of liver damage in chronic hepatitis C. METHODS: A total of 145 patients with chronic hepatitis C virus (HCV) infection (36 patients with persistently normal ALT values; 109 patients with elevated ALT levels) and 160 uninfected healthy controls were examined for HLA-DQA1, DQB1, and DRB1 molecules by using polymerase chain reaction-sequencing based typing (PCR-SBT). RESULTS: Among the patients chronically infected with HCV, the frequencies of DQA1*0501, DQB1*0301, and DRB1*0401 alleles were significantly increased in the normal ALT group compared with those with abnormal ALT levels, whereas that of DQB1*0201 was significantly lower. As compared to uninfected healthy controls, DQA1*0501, DQB1*0301, and DRB1*0401 allele frequencies were also statistically higher in the normal ALT group, whereas that of DQB1*0201 was the inverse. The haplotype frequencies of DQA1*0301-DQB1*0301, DQA1*0501-DQB1*0301, and DRB1*1101-DQB1*0301 were found to be significantly higher in the normal ALT group. Multivariate logistic regression indicated that female sex, and the DQB1*0301 allele and DRB1*0401 allele were independently associated with normal ALT values, whereas DQB1*0201 allele was the inverse. CONCLUSIONS: These results suggest that particular HLA alleles may have an influence on the serum ALT level of chronic HCV infection as a host genetic factor in the Chinese population. The DQA1*0501, DQB1*0301, and DRB1*0401 alleles, and the DQA1*0301-DQB1*0301, DQA1*0501-DQB1*0301, and DRB1*1101-DQB1*0301 haplotypes seem to be associated with low hepatitis activity; whereas DQB1*0201 allele is closely correlated with the progression of liver injury in chronic HCV infection.

[CD4+ CD25+ regulatory T cells suppress CD4+ T cell responses in patients with persistent hepatitis C virus infection].

OBJECTIVE: To study the role of CD(4)(+) CD(25)(+) regulatory T cells (CD(4)(+) CD(25)(+) Treg cells) in CD(4)(+) T cell responses in patients with persistent infection of hepatitis C viruses. METHODS: Flow cytometry was used to determine the number of CD(4)(+) CD(25)(+) Treg cells and intracellular cytokine production by CD(4)(+) CD(25)(+) Treg cells in patients with chronic HCV infection. To assess their regulatory properties CD(4)(+) CD(25)(+) Treg cells were co-cultured with CD(4)(+) CD(25)(-) T cells from patients or controls; the expressions of Foxp3 were measured by RT-PCR. RESULTS: CD(4)(+) CD(25)(+) Treg cells comprised (13.5 +/- 1.8)% of peripheral CD(4)(+) T cells in the blood of persistent hepatitis C virus infected patients, which was significantly higher than that of healthy controls (5.3 +/- 0.8)% (P = 0.004). CD(4)(+) CD(25)(+) Treg cells highly expressed Foxp3 and mainly synthesized IL-10; CD(4)(+) CD(25)(+) Treg cells dramatically suppressed the proliferation of CD(4)(+) T cells and the production of IFN gamma; the suppressive activity of CD(4)(+) CD(25)(+) Treg cells in patients with persistent HCV-infection was higher than that in healthy controls (P = 0.034). These effects were dose-dependent but IL-10 and transforming growth factor beta independent. CONCLUSION: Patients with persistent hepatitis C virus infection show an increased number and suppressive activity of CD(4)(+) CD(25)(+) Treg cells, which could function in a highly regulatory capacity to suppress Th1 response.

[Isolation, identification and functional characterization of human CD4+ CD25+ Treg cells from human peripheral blood].

AIM: To isolate CD4(+) CD25(+) Treg cells from human peripheral blood, and study their functional characteristics. METHODS: The expressions of Foxp3 in human CD4(+) CD25(+) Treg cells were test by RT-PCR. The regulatory properties of CD4(+) CD25(+) Treg cells were assessed by co-culturing with CD4(+) CD25(-) T cells and CD8(+) T cells, or adding exogenous IL-2. The detection of intracellular cytokine production of IL-4, IL-10 and IFN-gamma was done by flow cytometry. RESULTS: CD4(+) CD25(+) Treg cells highly expressed Foxp3 and mainly synthesized IL-10 that suppressed the proliferation of CD4(+) CD25(-) T and CD8(+) T cells. Its suppressive function was reversed by high concentration of IL-2 and (or) IL-4. CONCLUSION: CD4(+) CD25(+) Treg cells exhibited a subpopulation of immunoregulatory T cells with suppressive function, which could be reversed by high concentration of IL-2.

Human leukocyte antigen class II DQB1*0301, DRB1*1101 alleles and spontaneous clearance of hepatitis C virus infection: a meta-analysis.

AIM: To assess the associations of human leukocyte antigen (HLA) class II DQB1*0301 and/or DRB1*1101 allele with spontaneous hepatitis C virus (HCV) clearance by meta-analysis of individual dataset from all studies published till date. METHODS: To clarify the impact of HLA class II polymorphisms on viral clearance, we performed a meta-analysis of the published data from 11 studies comparing the frequencies of DQB1*0301 and DRB1*1101 alleles in individuals with spontaneous resolution to those with persistent infection. As we identified the heterogeneity between studies, summary statistical data were calculated based on a random-effect model. RESULTS: Meta-analyses yielded summary estimates-odds ratio (OR) of 2.36 [95%CI (1.62, 3.43), P<0.00001] and 2.02 [95%CI (1.56, 2.62), P<0.00001] for the effects of DQB1*0301 and DRB1*1101 alleles on spontaneous clearance of HCV, respectively. CONCLUSION: These results support the hypothesis that specific HLA class II alleles might influence the susceptibility or resistance to persistent HCV infection. Both DQB1*0301 and DRB1*1101 are protective alleles and present HCV epitopes more effectively to CD4(+)T lymphocytes than others, and subjects with these two alleles are at a lower risk of developing chronic HCV infection. Large, multi-ethnic confirmatory and well-designed studies are needed to determine the host genetic determinants of HCV infection.

[Hepatitis c virus genotype research by ABC programs of 5'-NCR restriction endonuclease digestion].

OBJECTIVE: In order to fully understand hepatitis c virus (HCV) genotype 3b, 1a, 2b and 6a infection in China, We built HCV 5'-noncoding region (5'-NCR) of different genotypes and subtypes. METHODS: The classification HCV into variable genotypes (subtypes) was carried on by programs A, B and C A. Using a combination of three restriction endonuclease BHH' (BsrB I, Hae II, Hinf I) digestions at the same time. The distinct genotypes were classified into 5 groups: genotype 1 (1a, 1b), 6a, 2 (2a, 2b), genotype 3 (3a, 3b), genotype4 (4a). B. With regard to genotype 1, we could distinguish subtype 1a from 1b using BstU I digestion. C. Using restriction endonuclease Hae III, genotype 2a, 2b, 3b, 4a, 6a are differentiated respectively. RESULTS: (1) HCV genotype 1a, 1b, 2a, 2b, 3a, 3b, 4a, 6a are fully discriminated by comparison with the genotypes regular samples. (2) Of the 93 patients, HCV genotype distribution in China was 66.67% for 1b, 18.28% for 2a, 3.23% for 1b/2b, 3b, 2b respectively. 2.15% for 2a/2b, 1b/2a respectively. 1.08% for 1a. CONCLUSION: This research indicated that adoption of HCV 5'-NCR A B C restriction endonuclease digestions techniques, might be sensitive and efficient to detect HCV and discriminate HCV genotype (subtypes) 1a to 6a.