BackgroundAlpha-fetoprotein (AFP) is a tumor-associated glycoprotein that functions in regulation of both ontogenic and oncogenic growth. Recent study showed that AFP can induce apoptosis or impair monocyte-derived dendritic cell (MDDC) function. However, it is still unclear which AFP domain (D-AFP) plays major role in this function.ResultsAs expected monocytes cultured in the presence of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Interleukin-4 (IL-4) developed into MDDC. Up-regulation of HLA-DR and CD11c as well as loss of CD14 molecules could be observed. Full length AFP (FL-AFP), domain 2 AFP (D2-AFP) and D3-AFP, but not D1-AFP, significantly inhibited the expression of HLA-DRhigh/CD11chigh and CD80+/CD86high molecules. In contrast, CD83 expression was substantially down-regulated in all samples. Expression of CD40 was significantly suppressed by FL-AFP but not by any D-AFPs. Finally, both FL-AFP and D-AFP impaired the MDDC ability to secrete IL-12 (p70).ConclusionsD2- and D3- but not D1-AFP extensively suppresses the MDDC function. All the recombinant AFP proteins impaired the ability of MDDC to secrete IL-12.

The molecular epidemiological study of hepatitis B virus (HBV) in Indonesia is still limited. This study was aimed to identify the prevalence of HBV pre-S deletion/insertion mutations, and to assess the association of pre-S deletion mutation with liver disease progression in Indonesia. Pre-S mutations were identified by direct sequencing. Of the 265 subjects, 32 samples (12.1%) harbored pre-S deletion/insertion mutations. The prevalence of those pre-S mutations was 2.7% (2/75), 12.9% (8/62), 16.7% (11/66), and 17.7% (11/62) in asymptomatic carrier, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma groups, respectively. Statistical analysis showed significant difference among them (P = 0.024). In HBV genotype B (HBV/B), pre-S1, pre-S1/S2, and pre-S2 deletion mutations were detected respectively in 3 (17.6%), 4 (23.5%), and 9 (52.9%) of 17 samples. On the other hand, in HBV/C, 12 of 15 samples (80.0%) showed a pre-S2 deletion mutation, and only 2 samples (13.3%) demonstrated a pre-S1/S2 deletion mutation. These results suggest that in HBV/B deletion mutation tends to occur in pre-S1 or pre-S1/S2 region, while in HBV/C the deletion mutation usually occurs in the pre-S2 region. Analysis of complete genome of four viruses confirmed that 3 isolates were classified into HBV/B3, and 1 isolate was HBV/C1. However, SimPlot and BootScan analyses showed that isolate 08.10.002 was an intragenotypic recombinant between HBV/B3 and HBV/B4. As conclusion, the prevalence of HBV pre-S mutations was relatively low in Indonesian patients compared to those from Taiwan, Japan, and other Asian countries. There was a weak association between pre-S deletion mutation and progressive liver disease.

Pre-S2 start codon mutation was higher in Indonesian patients compared to other Asian countries, and its prevalence was associated with advanced liver disease, particularly in HBeAg⁺ patients.

BackgroundThe Minangkabau is one of the major ethnic groups in Indonesia. Previous studies with a limited number of samples have shown a different prevalence of HBV/C in the Minangkabau compared to the Indonesian population in general. The aim of this study was to assess the HBV genotype distribution pattern and the prevalence of pre-S, T1753V and A1762T/G1764A mutations among the Minangkabau HBV carriers. The samples were collected from Padang, West Sumatera and from western Java. Mixed primers for specific genotypes were used to determine the HBV genotype. Pre-S or S genes were amplified, sequenced and aligned with reference sequences from GenBank to derive a phylogenetic tree for subgenotyping. Pre-S genes were also analyzed for mutations. The basal core promoter (BCP) region was amplified and directly sequenced to analyze T1753V and A1762T/G1764A mutations.ResultsThe predominant HBV genotype among the Minangkabau HBV carriers (n=117) was C (72.6%) followed by B (24.8%) and co-infection with B and C (2.6%). The prevalence of pre-S mutations, including both the pre-S deletion and pre-S2 start codon mutation, was 41.0%, and the T1753V and A1762T/G1764A mutations were found in 51.9% and 71.2% respectively. HBV/C1 was the predominant HBV subgenotype in the Minangkabau HBV carriers, and was found in 66.2%, followed by B3, B7, C8, B2, B9, C2, and C10 (18.3%, 7.0%, 2.8%, 1.4%, 1.4%, 1.4%, and 1.4% respectively). From samples that were found to be co-infected with HBV B and C, two samples were successfully cloned and subgenotyped, including one with mixed subgenotypes of B3 and C1, and another one with mixed subgenotypes of B7, C1, putative intergenotypic of B/A, and C/A. Furthermore, three samples from donors of non-Minangkabau ethnicity from Padang were found to be infected with an intragenotypic recombination form, including a putative recombinant of B8/B3 and B9/B7.ConclusionHBV/C with subgenotype C1 was the predominant HBV genotype among HBV carriers of Minangkabau ethnicity. The prevalence of pre-S, A1762T/G1764A, and T1753V mutations was higher among the Minangkabau compared to Indonesian HBV carriers in general.