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ABSTRACT: Aim: D-3-phosphoglycerate dehydrogenase (3-PHGDH) was identified as a putative target of autoantibodies in autoimmune hepatitis (AIH). The aims of the present study were to detect anti-3-PHGDH in patients with AIH and other chronic liver diseases and to analyze their clinical relevance. Methods: Human 3-PHGDH gene was cloned and expressed in Escherichia coli and used in enzyme-linked immunosorbent assays and Western blots. Serum from patients with AIH (n = 101), primary biliary cirrhosis (PBC, n = 122), chronic hepatitis C (CHC, n = 117), chronic hepatitis B (CHB, n = 112), and from patients with other autoimmune disease (n = 125) were investigated. Results: The highest incidence and activity of anti-PHGDH was observed in AIH patients. Thirty-two of 40 untreated (80%) and 37 of 61 AIH patients treated with corticosteroid (60.7%) were positive. Antibody titers decreased significantly during corticosteroid treatment. 15.8% of PBC patients, 9.8% of CHB and 12.8% of CHC patients, were anti-PHGDH-positive, with less than 12% of patients positive with other autoimmune diseases via reactions with recombinant 3-PHGDH protein. Conclusion: Anti-PHGDH were detected in chronic liver diseases. They occur predominantly in AIH, and corticosteroid treatment seems to decrease antibody titers. Whether the antibodies are primary or secondary phenomena and whether they are related to the etiology or pathogenesis, at least in a subgroup of patients with chronic liver diseases, has still to be evaluated.
Hepatology Research 06/2011; 41(9):867-76. · 2.20 Impact Factor
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ABSTRACT: To identify soluble liver antigen (SLA)-specific dominant epitopes and analyse the correlation between SLA-specific T cell response and the status of the disease.
A cross-sectional analysis of SLA-specific T cell responses to 54 overlapping peptides covering the entire SLA sequence was performed using an interferon (IFN)-γ ELISpot assay in 31 patients with auto-immune hepatitis (AIH)-1, 15 patients with primary biliary cirrhosis, 16 hepatitis B virus, seven hepatitis C virus infection and 10 healthy subjects, in order to assess the correlation between SLA-specific T cell responses and the clinical outcome.
Soluble liver antigen-specific IFN-γ responses in AIH were significantly more frequent in AIH patients (58.1%) than those in controls (6.7% in PBC, P=0.001; 4.3% in hepatitis B/C, P<0.001 and 0% in healthy subjects, P=0.0015). Among 31 AIH patients, the frequency of recognition and the magnitude of response to SLA peptides in anti-SLA antibody-positive patients were higher and stronger than those negative for anti-SLA antibodies (P=0.02 and 0.037 respectively). We further analysed T-cell restriction and found that six individual SLA peptides (4, 9, 11, 12, 41 and 44) were recognized by CD4 T cells, and the most frequently recognized peptides were peptides 12 (61.1% of participants), followed by peptide 4 and peptide 44 (55.6 and 38.9% respectively). Moreover, a positive association was found between the breadth of recognition of SLA peptides and the indices of liver damage.
T cell response to SLA in Chinese patients with AIH is broad and associated with hepatocyte damage.
Liver international: official journal of the International Association for the Study of the Liver 05/2011; 31(5):721-9. · 3.82 Impact Factor
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Yan Zhao,
Yong-hong Zhang,
Lian-chun Liang,
Xin Zhang,
Qiang Zhang,
Yue-ke Zhu, Yan Liu,
Xia Feng,
Dong-mei Ma,
Yu-fen Tan,
Hao Wu,
Hui-ping Yan
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ABSTRACT: To describe the feature of different age patients with A-H1N1.
Cross-sectional study was performed in 95 patients who were confirmed to be infected with A-H1N1 from May, 2009 to July, 2009, in according to their age.
The average age of patients with A-H1N1 infection was 23.44 +/- 14.73. Accumulative prevalence in children and young adult reached 74.7% of total patients. There was a trend that the subclinical infection rate raised gradually from 0-15 years group to over 45 years group. The percent of lymphocyte in 0-15 years group was significantly higher than other age groups, P = 0.039. The average time of virus shedding were 6.5 +/- 2.10 days (from 2 days to 12 days) , and there were no significant difference in diverse age groups, P = 0.272. 13 out of 95 (13.7%) patients presented complications related with A-H1N1 infection, and 4 of 6 patients complicated with pneumonia were in the 0-15 years group.
The distribution of age in A-H1N1 infection is markedly different from seasonal influenza, with more cases in school children and young adults and fewer cases in older adults. Flu-like symptoms in children were apparent and pneumonia was the major complication in children.
Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology 06/2010; 24(3):218-20.
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ABSTRACT: To investigate the clinical significance of liver function and autoantibodies in patients with acute or chronic drug-induced liver injury.
51 patients with drug-induced liver injury were divided into acute drug induced liver injury group and chronic drug induced liver injury group, liver function and autoantibodies were compared between these two groups.
There was no significant difference (P more than 0.05) in alanine aminotransferase [(412.1+/-387.5) U/L and (376.0+/-319.7) U/L], aspartate aminotransferase [(352.5+/-457.9) U/L and (198.8+/-142.7) U/L], total bilirubin [(109.7+/-104.80)micromol/L and(102.4+/-135.7)micromol/L], direct bilirubin [(66.4+/-73.3)micromol/L and (61.2+/-72.1)micromol/L], alkaline phosphatase [(133.4+/-50.1) U/L and (147.4+/-97.3) U/L], gamma-glutamyltransferase [(139.9+/-134.1) U/L and (180.6+/-227.9) U/L], and albumin [(41.3+/-4.9) g/L and (39.8+/-5.3)g/L] between these two groups, however, the level of globulin [(25.1+/-5.3) g/L and (28.6+/-5.1) g/L] was significantly different between these two groups (P less than 0.05). The titers of Anti-nuclear antibody (ANA) and smooth muscle antibody (SMA) were less than or equal to 1:320 in patients with acute drug induced liver injury. The titers of ANA, antimitochondrial antibody (AMA), and SMA were more than or equal to 1:320 in most of the patients with chronic drug induced liver injury.
Liver function has no value in the diagnosis of acute or chronic drug induced liver injury. High titer autoantibodies are found in patients with chronic drug induced liver injury.
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 01/2010; 18(1):37-40.
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ABSTRACT: To analyze the etiology and clinical manifestations of 70 patients with hand-foot-mouth disease (HFMD).
The viral RNA from the pharynx swab samples were extracted and collected from 70 HFMD patients (of which, 60 cases were under 5 years old) to detect the 5'-UTR gene of EV, the Vp3-Vp1 genes of EV71 and Cox-A16 by utilizing the technique of RT-PCR.
Of 70 HFMD patients, 30 cases (42.8%, 30/70) were positive in enterovirus nucleic acid, including EV71 and Cox-A16, pharynx swab sample testing. While, of the enteroviral pathogen RNA-positive 30 cases, EV71 accounted for 66.7% (20/30). The proportion of etiological positive of 39 samples collected within 4 days after onset was 66.7% (26/39), but the probability of 31 samples collected after more than 5 days after onset was 12.9% (4/31), the difference was significantly (chi(2) = 20.4, P < 0.01).
HFMD patients were mainly infants and young children between 0-5 years old, but adults could also be attacked. The enterovirus detected was mainly EV71, and the pharynx swab samples should be collected within 4 days after onset to increase the related viral nucleic acid positive detection probability.
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] 10/2009; 43(10):872-4.
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ABSTRACT: To investigate the ability of secreting interferon-gamma (IFN-gamma) of the peripheral blood monocular cells (PBMC) stimulated by hepatitis B virus (HBV)-specific cytotoxic T lymphocyte (CTL) epitopes peptides and to analyze the difference of CTL immune response in patients with HBV infection.
Four HLA-A2-restricted HBV cytotoxic T lymphocyte epitopes [Tp: HBV polymerase 575-583 (FLLSLGIHL), Te1: envelope 28-39 (IPQSLDSWWTSL), Te2: envelope 183-191 (FLLTRILTI) and Tc: core 18-27 (FLPSDFFPSV)] were synthesized. Human leucocyte antigen (HLA)-A2 typing was detected by Flow cytometry. PBMCs which were isolated from patients with chronic hepatitis B(CHB), patients with chronic severe hepatitis B(CSH), subjects with past HBV infection(N1) and healthy blood donors (N2) were stimulated by the four HLA-A2-restricted HBV CTLs epitopes. Enzyme linked immunospot (ELISPOT) assay was used to detect the frequency of secreting IFN-gamma CTL in each group.
(1) HLA-A2 typing: 20 of 44 patients with CHB (45.5%) were HLA-A2 positive, 10/18 (55.6%) in CSH and 6/10 (60%) in group N1 were HLA-A2 positive.10 healthy blood donors' HLA-typing was detected in the early study.(2) ELISPOT results: (1) The total responses to the four epitopes in CHB, CSH, N1 and N2 groups were 50% (10/20), 10% (1/10), 83.3% (5/6) and 10% (1/10), respectively. The response in N1 group was significantly higher than that in CSH group (chi(2) = 9.000, P = 0.008) and N2 group (chi(2) = 9.000, P = 0.008). (2) The CTL average magnitude response to Tp epitope, Te1 epitope, Te2 epitope and Tc epitope was also significantly higher in past HBV infection group (77 SFC/10(6) PBMC, 59 SFC/10(6) PBMC, 100 SFC/10(6) PBMC and 57 SFC/10(6) PBMC, respectively) than that of CSH group (10 SFC/10(6) PBMC, 0 SFC/10(6) PBMC, 0 SFC/10(6) PBMC and 20 SFC/10(6) PBMC respectively, all P < 0.01) and N2 group (15 SFC/10(6) PBMC, 0 SFC/10(6) PBMC, 22 SFC/10(6) PBMC and 30 SFC/10(6) PBMC respectively, all P < 0.01).
This study indicates that the T cell immune response to HBV-specific epitopes might be detected either in patient with chronic HBV infection or with previous HBV infection. This response should be much higher in patients with past HBV infection, even the virus had been cleared for long time. These results demonstrate that HBV-specific CTL might play an important role in the clearance of the virus.
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] 08/2009; 43(8):690-4.
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ABSTRACT: To evaluate whether the D-3-phosphoglycerate dehydrogenase (Phgdh) correlative antibodies is crucial for AIH, we cloned Phgdh cDNA and constructed plasmid, then purified and identified the immunoreactivity of the recombinant protein, and established the enzyme linked immunosorbent assay (ELISA) to detect Phgdh autoantigen correlative antibodies in diagnosis of autoimmune hepatitis.
The constructed plasmid was transformed into E. coli. BL21(D3). This fusion protein was purified by Ni-NTA chromatography and its immunoreactivity was identified by SDS-PAGE and Western blot. The ELISA with the fusion protein was established first, then, the Phgdh autoantigen correlative antibodies in serum of patients with AIH (65) and patients with PBC (122) as well as chronic hepatitis B (CHB) (56), chronic hepatitis C (CHC) (117), and normal controls (60) were detected.
The sequence of Phgdh autoantigen gene was the same as the sequence reported on the genebank. The fusion protein was found about 60kD strip on SDS-PAGE. Western blot analysis showed that the fusion protein had immunoreactivity. When analyzing the serum by ELISA, the immune reactivity to Phgdh was detected in 66.15% of patients with AIH, 21.42% of patients with PBC, 12.50% of patients with CHB, 6.83% of patients with CHC, and 3.30% of normal individuals. The differences of prevalence between AIH patients and healthy controls as well as other diseases were of statistical significance (P less than 0.01).
The Phgdh cDNA is successfully cloned into E. coli BL21 (D3). The frequency of antibodies to Phgdh is much higher in patients with AIH than in patients with PBC, CHB, CHC and normal control. The antibodies to Phgdh may have utility in improved diagnosis of AIH.
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 06/2009; 17(5):378-82.
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ABSTRACT: To study the significance of anti-soluble liver antigen/liver-pancreas (anti-SLA/LP) in diagnosing and typing autoimmune hepatitis (AIH).
Six thousand patients with abnormal liver functions, who had their autoantibodies checked by immunofluorescent assay (IFA) and immune blotting assay, were reviewed retrospectively.
Of these 6000 patients with liver diseases, 84 were diagnosed AIH. Eighteen patients, 0.3% of the 6000, patients with abnormal liver functions, were SLA/LP antibody positive, of which 17 were with AIH-III [2/17 with AIH /primary biliary cirrhosis (PBC) overlap syndrome], and 1 with chronic hepatitis B. Sensitivity and specificity of SLA/LP antibody in diagnosing AIH were 20.2% and 99.7% respectively, and the positive prediction value was 94.44%. The antinuclear antibody (ANA) titer in the AIH-III group was significantly lower than that of the AIH-I group (P < 0.05). The age of patients with anti-SLA/LP was higher (58.8% were over 50 years old) than those without this antibody (52.2% were 30 to 50 years old). There were no significant differences between the type III and type I AIH regarding gender, age, abnormal degree of liver function, PTA, IgG, liver cirrhosis rates and response to immunosuppressive therapy.
Anti-SLA/LP is highly specific for diagnosing AIH. Comparing the clinical data of type III and type I AIH, we did not find significant differences between the two groups.
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 04/2007; 15(4):283-6.
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ABSTRACT: To analyze the clinical and laboratory features of anti-soluble liver antigen/liver-pancreas (SLA/LP) autoantibody positive patients with abnormal liver functions.
From July 1999 to August 2004, 4928 serum samples from patients with abnormal liver functions (ALT >40 U/L) were collected. A series of autoantibody examinations were carried out. Clinical manifestations and laboratory findings of 8 patients with anti-SLA/LP autoantibody positive were reviewed.
Among the 5500 serum samples, 8 cases (6 females and 2 males) with positive anti-SLA/LP autoantibodies were found with complete clinical information. The age of the patients was (27-76) years old. The case histories were from 2 years to 10 years. Of the 8 patients, 6 cases had liver cirrhosis and HBsAg-negative and anti-HCV-negative, active, 1 case had liver cirrhosis with HBsAg-positive, but HBVDNA negative; 1 case had liver cirrhosis and anti-HCV positive, but HCV RNA negative. The 8 cases were all ANA positive with titers of 31:320. Four cases were AMA positive and 2 among these 4 cases were M2 positive. The most frequent symptoms were fatigue, anorexia, nausea, jaundice, abdominal distention and edema of lower limbs. All patients had high hypergammaglobulinemia.
Anti-SLA/LP autoantibody was at a low detection rate in the study with females in preponderance, Clinical and laboratory characteristics of the 8 cases were consistent with those of the autoimmune hepatitis (AIH). Testing for anti-SLA autoantibodies helps in the diagnosis of AIH in many patients who may otherwise be misdiagnosed.
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 12/2005; 13(12):927-9.
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ABSTRACT: To study the clinical significance of the immunological characteristics in patients with primary biliary cirrhosis (PBC).
3000 patients with abnormal liver functions were examined for anti-nuclear antibodies (ANA), anti-mitochondrial antibodies (AMA), anti-smooth muscle antibodies (SMA) and anti-liver kidney microsomal antibody (LKM) using immunofluorescent assays (IFA). LKM-1, liver cytosolic-1 (LC-1), soluble liver antigen (SLA)/liver- pancreas antigen (LP) and subtype of AMA (M2, M4, M9) as well as ANA profile were detected by an immune blotting assay and an enzyme-linked immune absorbent assay (ELISA), respectively. Cytokines were tested by flow cytometry.
Of the 3000 patients with liver diseases, 52 (1.7%) were diagnosed with PBC. All the PBC cases were positive for AMA and M2. 94% of them showed high titer of AMA (> or = 1:320), and in 79% of them M2 was >200 RU/L, and 78% of them were ANA positive. Three main fluorescent patterns of ANA seen were nuclear membrane, nuclear dots and centromere patterns. Sjogren's Syndrome A/B (SS-A/B), homogenous, nucleolar or nuclear granular patterns were seen in only a few patients. IgM, ALP and GGT in PBC patients were significantly higher than those in hepatitis B related liver cirrhosis patients. The levels of IL-6, IL-10, TNF-alpha and IFN-gamma in PBC patients were higher than in the normal controls. Among the 52 PBC patients, 5 had autoimmune liver disease overlap syndromes. Two of them were SLA/LP positive, indicated as AIH type III and PBC overlapping, and 1 was LKM-1 positive showing AIH type II overlapping PBC, and 2 had ANA positive and were identified as AIH and PBC by liver biopsy.
The percentage of PBC in Chinese liver disease patients is about 1% to 2%. Most of the PBC patients have high levels of AMA and AMA-M2, IgM, ALP, GGT and several cytokines, indicating that abnormality of humeral and cellular immunity may be associated with the pathogenesis of PBC.
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 02/2005; 13(1):12-6.
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ABSTRACT: Silicon oxynitride (SiON) has received a great deal of attention in micro-electro-mechanical system (MEMS) integration due to its composition-dependent tunability in optical, electronic and mechanical properties. In this work, silicon oxynitride films with different oxygen and nitrogen content were deposited by RF magnetron sputtering. Energy dispersive X-ray (EDX) spectroscopy and Fourier-transform infrared (FT-IR) spectroscopy were employed to characterize the SiON films with respect to stoichiometric composition and atomic bonding structure. Time-dependent plastic deformation (creep) of SiON films were investigated by depth-sensing nanoindentation at room temperature. Young's modulus and indentation-hardness were found correlated with the nitrogen/oxygen ratio in SiON films. Results from nanoindentation creep indicated that plastic flow was less homogenous with increasing nitrogen content in film composition. Correspondingly, a deformation mechanism based on atomic bonding structure and shear transformation zone (STZ) plasticity theory was proposed to interpret creep behaviors of sputtered SiON films.
Materials Science and Engineering: A.
