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Hepatology 03/2013; · 11.66 Impact Factor
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ABSTRACT: BACKGROUND: MicroRNA, as an important regulator of gene expression, has been found to be associated with several diseases. MicroRNA expression profiles have been identified in several autoimmune diseases such as RA, SLE and MS. However, the expression profile in PBMCs from PBC patients and the role of microRNA in PBC remained unclear. The present study aimed to explore abnormal microRNAs regulation in PBC. METHODS: MicroRNA array was performed in PBMCs obtained from PBC patients versus healthy controls. Then, 6 of the 17 differentially expressed microRNAs were confirmed using qRT-PCR. Based on Bioinformatics analysis, we identified the potential biological processes, significant signaling pathways affected by these microRNAs and generated the microRNA-gene network. RESULTS: According to microRNA array, a total of 17 microRNAs were found to be differentially expressed. 6 microRNAs have been validated using qRT-PCR, and the results were consistent with microRNA array analysis. The bioinformatics analysis showed that the potential target genes of these microRNAs were involved in cell proliferation, cell differentiation, apoptosis, signal transduction. Similarly, these microRNAs also affected endocytosis, MAPK signaling pathway, TGF-β signaling pathway, Wnt signaling pathway, calcium signaling pathway, etc. CONCLUSION: In the present study, 17 microRNAs were identified to be differentially expressed in PBMCs from PBC patients. Functional bioinformatics analysis demonstrated that prediction genes targeted by these microRNAs were involved in multiple biological processes and signaling pathways. The present study offers intriguing new perspectives on the involvement of microRNA in PBC, but the precise mechanisms need to be validated further.
Journal of Gastroenterology and Hepatology 11/2012; · 2.87 Impact Factor
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ABSTRACT: BACKGROUD: Anti-SSA and -SSB antibodies are clinically important antinuclear antibodies in patients with systemic rheumatic diseases.
We evaluated fluorescence characteristics and clinical significance of anti-SSA and -SSB and explored whether identification of these antibodies was necessary in clinical application.
Of 4,978 consecutive samples, 259 showed anti-SSA or -SSB reactivity, clinical information of which were analyzed. Compared with SSA+SSB- and SSA-SSB+ group, SSA+SSB+ group showed a lower proportion (0.5%) of negative specimens detected with antinuclear antibody assay and a higher proportion (53.5%) of specimens with high titer. Anti-SSA- and/or -SSB-positive samples presented various patterns. However, 64.6% of SSA+SSB+ samples presented speckled pattern, significantly higher than SSA+SSB- and SSA-SSB+ samples. A total of 475 specimens containing anti-SSA or -SSB were obtained from 302 individuals. Clinical information was obtained for 259 of them, which were further analyzed. The prevalence of Sjögren syndrome (SS) was significantly higher, and that of other diseases was lower in SSA+SSB+ than in SSA+SSB- group. Of the 259 individuals, 71 anti-SSA- and/or -SSB-positive patients had blood drawn on 2 or more occasions over the 2-year study period. The number of tests per patient was 2.7 ± 1.1. In 7 of the 71 patients, anti-SSA was observed in some but not all samples, so was anti-SSB in 6.
In conclusion, the identification of anti-SSA and -SSB antibodies is necessary, when corresponding diseases are suspected. The specificity of anti-SSA for the diagnosis of SS could be improved, when combined with anti-SSB. SS patients need not be identified frequently for anti-SSA and -SSB because of their stability.
Journal of Clinical Laboratory Analysis 11/2012; 26(6):447-51. · 1.38 Impact Factor
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ABSTRACT: BACKGROUND: Previous studies have shown the genetic association of tumor necrosis factor (TNF)-α polymorphisms and susceptibility to primary biliary cirrhosis (PBC), but the results of individual studies have remained contradictory. Therefore, a meta-analysis was carried out to evaluate comprehensively the association of TNF-α polymorphisms and susceptibility to PBC. METHODS: The relevant published articles were searched in PubMed, EMBASE, and Cochrane library. Data were extracted using standardized forms and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each study. Pooled data were estimated by fixed-effects and random-effects models when appropriate. We analyzed the association between the 'A' allele at position -308(rs1800629) and -238(rs361525) and the risk of PBC. RESULTS: We examined eight publications, showing that all eight studies discussed the TNF-α -308(rs1800629) polymorphism; four studies were relevant with -238(rs361525). No significant associations were found between the 'A' allele frequency of rs1800629 and rs361525 and the risk of PBC in the overall population (OR=0.89, 95% CI 0.71-1.11, P=0.91; OR=0.98, 95% CI 0.66-1.47, P=0.93) and in Whites (OR=0.94, 95% CI 0.74-1.19, P=0.58; OR=1.01, 95% CI 0.64-1.59, P=0.97). Besides, it was also found that the genotype (AA+AG vs. GG, GG+AG vs. AA) was not linked to susceptibility to PBC. CONCLUSION: The meta-analysis indicated that none of these two polymorphisms (-308G/A and -238G/A) showed any significant association with the risk of PBC.
European journal of gastroenterology & hepatology 09/2012; · 1.66 Impact Factor
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ABSTRACT: Several studies have indicated that primary biliary cirrhosis (PBC) may be associated with increased risk of some cancers, but the results are controversial. We conducted a systematic review of studies to examine the association of PBC with cancer risk by meta-analysis. We searched the PubMed and EMBASE databases for English-language studies published before November 2011. Studies were included if they reported relative risk estimates with 95% confidence intervals (CIs) or related data for the association between PBC and cancer risk. Approximately 16,300 PBC patients from several countries were included in this analysis. Of the 3510 titles identified, 16 publications involving 17 studies meeting the inclusion criteria were included in the meta-analysis. Compared with the general population, PBC patients had a significantly higher risk of overall cancer (pooled rate ratio [RR], 1.55; 95% CI, 1.28-1.83) and hepatocellular carcinoma (HCC) (pooled RR, 18.80; 95% CI, 10.81-26.79). For stomach and pancreas cancers, the results of one study that only examined male patients with PBC indicated that PBC patients had increased risk of stomach cancer and pancreatic cancer, whereas the results of other studies of mixed-sex patients showed no significant association. Therefore, despite inconsistent results, the meta-analysis could not be conducted for assessing the association. PBC was not significantly associated with increased risk of other cancers. Conclusion: The present systematic review and meta-analysis demonstrate that PBC is closely associated with a greater risk of overall cancer and HCC, but not with other cancers. The data regarding the association between PBC and risks of several cancers need to be further confirmed in future studies. (HEPATOLOGY 2012).
Hepatology 04/2012; 56(4):1409-17. · 11.66 Impact Factor
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ABSTRACT: Some studies have reported that serum CA125 level is elevated in SLE patients, and elevated CA125 level may be associated with kidney involvement and disease activity in SLE. However, none of the previous studies controlled confounding variables and the results remained controversial. The present study was aimed to investigate whether elevated serum CA125 level is independently associated with clinical and laboratory features of SLE by excluding various confounders in Chinese patients.
A total of 156 SLE patients, consisting of 139 women and 17 men, were included in the study. Some clinical and laboratory characteristics of the patients were obtained by medical record review. Serum CA125 levels were measured by electrochemiluminescence immunoassays.
Compared with patients with normal CA125, those with elevated CA125 had significantly more serositis (37.5% vs. 1.9%, p<0.001) and lung involvement (37.5% vs. 12%, p=<0.001), higher SLEDAI scores (p<0.007). Furthermore, disease duration was significantly longer in those with elevated CA125. Univariate logistic regression analysis showed that elevated serum CA125 level was closely associated with disease duration (OR, 95%CI:1.005, 1.001-1.010; p=0.014), serositis (OR, 95%CI: 32.258, 6.993-142.857; p<0.001), renal involvement (OR, 95%CI: 2.283, 1.114-4.673; p=0.024), lung involvement (OR, 95%CI: 4.386, 1.927-10.000; p<0.001) and SLEDAI scores (OR, 95%CI: 1.098, 1.027-1.174; p=0.006). After controlling for various confounding variables, serositis and disease duration were the only two clinical variables significantly associated with elevation of serum CA125 level. The best cut-off value for CA125 using the ROC curve was 38 kU/L (sensitivity 85%, specificity 75%) and the area under the ROC curve was 0.777 with 95%CI of 0.685-0.868 (p<0.001). Furthermore, the serum CA125 levels can fall into the normal range again with the improvement of serositis.
Of various clinical and laboratory variables of SLE, only serositis is independently associated with serum CA125 elevation.
Clinical and experimental rheumatology 01/2012; 30(1):93-8. · 2.15 Impact Factor
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ABSTRACT: Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by intrahepatic bile-duct destruction, cholestasis, and fibrosis. It can lead to cirrhosis and eventually liver failure. PBC also shows some regional differences with respect to incidence and prevalence that are becoming more pronounced each year. Recently, researchers have paid more attention to PBC. To evaluate the development of PBC research during the past 11 years, we determined the quantity and quality of articles on this subject. We also compared the contributions of scientists from the US, UK, Japan, Italy, Germany, and China.
The English-language papers covering PBC published in journals from 2000 through 2010 were retrieved from the PubMed database. We recorded the number of papers published each year, analyzed the publication type, and calculated the accumulated, average impact factors (IFs) and citations from every country. The quantity and quality of articles on PBC were compared by country. We also contrasted the level of PBC research in China and other countries.
The total number of articles did not significantly increase during the past 11 years. The number of articles from the US exceeded those from any other country; the publications from the US also had the highest IFs and the most citations. Four other countries showed complex trends with respect to the quantity and quality of articles about PBC.
The researchers from the US have contributed the most to the development of PBC research. They currently represent the highest level of research. Some high-level studies, such as RCTs, meta-analyses, and in-depth basic studies should be launched. The gap between China and the advanced level is still enormous. Chinese investigators still have a long way to go.
PLoS ONE 01/2012; 7(4):e35366. · 4.09 Impact Factor
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ABSTRACT: The results from previous studies on association of TLR9 polymorphisms with the risk of systemic lupus erythematosus (SLE) remained contradictory. Therefore, a meta-analysis was performed to assess the association between TLR9 polymorphisms and SLE susceptibility. A literature-based search was conducted to identify all relevant studies. Pooled data were estimated by fixed- and random-effects models when appropriate. We examined seven publications, showing that there were only three polymorphisms (-1486C/T, +1174A/G and +1635C/T) existing in Asian populations. The meta-analysis indicated that none of these three polymorphisms showed any significant association with SLE risk in Asian populations. In conclusion, the present study indicates that TLR9 polymorphisms are not candidates for susceptibility to SLE, at least, in eastern Asian population. Furthermore, a large number of studies should be performed to explore the association of TLR9 polymorphisms with the risk of SLE in other populations, such as Europeans, Americans and Africans.
Cytokine 12/2011; 57(2):282-9. · 3.02 Impact Factor
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ABSTRACT: The aim of this study was to investigate the prevalence of autoantibodies in various liver diseases and evaluate the performance parameters of AMA, ANA and their combinations for PBC.
This study enrolled 115 PBC patients, 695 patients with other liver diseases and 105 healthy subjects.
AMA were detected mainly in PBC patients, while ANA were detected in all categories. The high titer and multiple nuclear dot, rim-like and centromere (MRC) patterns of ANA were found in the majority of PBC patients, in contrast to moderate titers and other patterns. All the liver diseases but HAV and NAFLD had significantly independent association with ANA. The combination of MRC patterns and AMA showed superior performance parameters for PBC.
Although ANA can occur in various liver diseases, high titer and MRC patterns of ANA are more specific for PBC. The combination of MRC patterns and AMA has superior performance for PBC.
Clinical biochemistry 09/2011; 45(3):203-6. · 2.02 Impact Factor
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ABSTRACT: The aim of this study is to investigate the associations of serum urea, creatinine and uric acid levels with clinical and laboratory characteristics, independent of lupus renal involvement in SLE patients. A total of 191 SLE patients were included in the present study. Some clinical and laboratory characteristics of the patients were obtained by medical record review. The results showed that serum urea, creatinine and uric acid levels seemed to be associated with several clinical and laboratory characteristics of SLE. However, multivariate logistical regression analysis indicated that increasing serum urea levels were positively associated with disease duration and thrombocytopenia, but negatively with arthritis and skin rash. Compared with quartile 1 of urea, the ORs of quartile 2, quartile 3 and quartile 4 were, respectively, 1.008 (0.997-1.015, P = 0.189), 1.010 (1.001-1.019, P = 0.038) and 1.014 (1.004-1.024, P = 0.008) with increasing disease duration; 1.912 (0.516-7.088, P = 0.332), 10.126 (2.771-36.997, P = 0.000) and 5.583 (1.285-24.266, P = 0.022) with thrombocytopenia; 0.864 (0.331-2.254, P = 0.765), 0.516 (0.18-1.475, P = 0.217) and 0.162 (0.047-0.557, P = 0.004) with arthritis; and 0.342 (0.135-0.868, P = 0.024), 0.215 (0.074-0.622, P = 0.005) and 0.332 (0.097-1.13, P = 0.078) with skin rash. Increasing serum creatinine levels were positively associated with sex, disease duration and SLEDAI, but negatively with skin rash. Compared with quartile 1 of creatinine, the ORs of quartile 2, quartile 3 and quartile 4 were, respectively, 2.993 (0.282-31.74, P = 0.363), 7.937 (0.861-73.18, P = 0.068) and 13.411 (1.32-36.246, P = 0.028) with male, 1.011 (1.002-1.02, P = 0.017), 1.002 (0.991-1.013, P = 0.684) and 1.018 (1.008-1.028, P = 0.001) with increasing disease duration; 1.112 (1.006-1.228, P = 0.038), 1.065 (0.959-1.183, P = 0.239) and 1.140 (1.022-1.272, P = 0.019) with increasing SLEDAI; and 0.303 (0.119-0.771, P = 0.012), 0.282 (0.104-0.76, P = 0.012) and 0.174 (0.052-0.584, P = 0.005) with skin rash. Increasing serum uric acid levels were only positively associated with erythrocytopenia. Compared with quartile 1 of uric acid, the ORs of quartile 2, quartile 3 and quartile 4 were, respectively, 0.910 (0.37-2.239, P = 0.837), 2.147 (0.901-5.116, P = 0.085) and 3.079 (1.211-7.828, P = 0.018) with erythrocytopenia. The present study demonstrated that, except for reflecting renal function, serum urea, creatinine and uric acid exert separate clinical significances in SLE.
Rheumatology International 07/2011; 32(9):2715-23. · 1.88 Impact Factor
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ABSTRACT: The aim of this study was to investigate the serum bilirubin levels in SLE patients and their associations with clinical and laboratory characteristics of SLE. There were 198 SLE patients in this study, of whom 7 cases with tobacco smoking or alcohol intake were excluded. Some clinical and laboratory characteristics of the patients were obtained by medical record review. In addition, 154 age- and sex- matched healthy volunteers with no histories of SLE, liver diseases, and other autoimmune or inflammatory diseases were randomly recruited into this study. The serum bilirubin levels were lower in SLE patients without liver diseases than in healthy controls (P = 0.000). Univariate logistic analysis demonstrated that hypertension, lupus renal involvement, positive anti-dsDNA antibody, C3, C4, hsCRP, and albumin remained as impact factors of total bilirubins; lupus renal involvement, ESR, IgG, globulin, and ALT, as impact factors of direct bilirubins; and lupus renal involvement, positive anti-dsDNA antibody, C3, C4, hsCRP, and albumin, as impact factors of indirect bilirubins. However, multivariate logistic analysis showed that only hsCRP remained as an independent positive impact factor of total bilirubins, lupus renal involvement as an independent negative impact factor of direct bilirubins, and hsCRP and albumin as independent positive impact factors of indirect bilirubins. In conclusion, serum bilirubin levels are decreased in SLE and the decreased bilirubin levels could be associated with inflammatory process and lupus renal involvement of SLE.
Rheumatology International 06/2011; 32(8):2423-30. · 1.88 Impact Factor
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ABSTRACT: Aim: This meta-analysis was conducted to provide more precise evidence for association between primary biliary cirrhosis (PBC) and smoking and some other factors. Methods: We searched the databases PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure up to 31 December 2010. Data were extracted by two persons independently. Homogeneity of effects across studies was assessed using the χ(2) -test statistic and quantified by I(2) . Odds ratio (OR) and 95% confidence intervals (CI) were calculated based on fixed- or random-effects models. The publication bias was analyzed by Egger and Begg tests. Results: A total of five studies were selected according to inclusion criteria. With the fixed-effects model, the pooled OR for PBC and smoking and family history of PBC were 1.67 (95% CI = 1.41-1.92) and 7.56 (95% CI = 1.90-13.22). With the random-effects model, the pooled OR for thyroid disease and urinary tract infection (UTI) were 3.08 (95% CI = 0.84-5.32) and 2.02 (95% CI = 1.40-2.65), respectively. No evidence of publication bias was observed by means of Begg and Egger tests for the factors. Conclusion: This meta-analysis suggested that smoking, family history of PBC and UTI were strongly associated with PBC in a white population by systematic review of five existing studies, and the association remains to be validated in other populations.
Hepatology Research 06/2011; 41(6):572-8. · 2.20 Impact Factor
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ABSTRACT: Some polymeric forms of immunoglobulin free light chains (FLCs) have been identified, such as dimer, trimer and tetramer, and the quantitative nephelometric assay of kappa and lambda light chains is very important to the diagnosis and management of multiple myeloma (MM), primary systemic amyloidosis (AL), etc. But, whether polymeric molecules could affect the results of the nephelometric assay, is rarely reported.
12 urinary samples from patients with light-chain MM were separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and every sample was run with reduced and nonreduced sample buffer in one gel. Urinary kappa and lambda light chains were measured on the BNII nephelometer. We then added 3 microL beta-mercaptoethanol (2-ME) to the samples to transform the dimers into monomeric forms and measured them again.
10 samples showed obvious dimers by SDS-PAGE, of which 2 samples were kappa light chain dimers. Six samples had decreased quantitative results contrasted with the former values. The two samples of kappa light chain dimers decreased more obviously.
The light chain dimer combined with more antibodies than the monomer and a larger antigen-antibody complex was formed. The larger complex could magnify the reaction between antigen and antibody of the nephelometric assay and therefore false elevated results could measured.
Clinical laboratory 01/2011; 57(1-2):53-7. · 0.90 Impact Factor
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ABSTRACT: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by abnormal production of autoantibodies and proinflammatory cytokines. Although interleukin-33 (IL-33), a novel number of the IL-1 family, has been reported to have proinflammatory effects, the association of IL-33 with SLE has remained unknown. The aim of this study was to examine whether the serum IL-33 level is associated with SLE. A total of 70 patients with SLE were recruited. Sera from these patients were obtained at their visit and were compared to sera from 40 healthy controls or 28 patients with rheumatoid arthritis (RA) for IL-33 level. Furthermore, blood samples from patients with SLE were determined for various SLE-related laboratory variables, including blood routine, complements, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and some autoantibodies. Serum IL-33 level was significantly increased in patients with SLE, compared with healthy controls, but was lower than that with RA. In patients with SLE, most clinical and laboratory characteristics did not correlate with serum IL-33 levels, with exceptions of thrombocytopenia, erythrocytopenia, anti-SSB antibody, ESR, CRP and IgA. By Spearman's correlation coefficient, patients with SLE showed close correlation of IL-33 with ESR, CRP and IgA, and by multivariate logistic regressions, patients with SLE showed significantly independent association of IL-33 with thrombocytopenia, erythrocytopenia and anti-SSB antibody. Our results suggest that IL-33 may play a role in acute phase of SLE, but it was not associated with course of the disease. Moreover, IL-33 may exert biologic effects on erythrocytes and platelets or their precursors in SLE.
Clinical and Experimental Medicine 10/2010; 11(2):75-80. · 1.58 Impact Factor
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ABSTRACT: The aim of the present study is to assess the association of elevated serum uric acid (UA) with lupus nephritis (LN) in systemic lupus erythematosus (SLE) patients. A total of 130 SLE patients were recruited, of whom 73 patients developed LN. Blood samples were obtained for determination of uric acid, complement 3 (C3), C-reactive protein (CRP) and some autoantibodies including anti-double-stranded DNA, -Smith, -SSA, -SSB, -U1RNP, SCL-70, and -Jo-1 antibodies. Correlations of UA with LN were assessed. UA was an independent risk factor for LN [odds ratio (95% CI): 1.01 (1.005-1.014); P=0.0000]. The best cut-off value for UA using the ROC curve was 330 μmol/L (sensitivity 78.1% and specificity 75.4%) and the area under the ROC curve was 0.803±0.039 (95% CI: 0.727-0.878, P=0.000). Spearman's correlation coefficient analysis showed negative association of UA with C3 in SLE patients with LN (r=-0.356, P=0.002), but no association in those without LN. No correlations were found between UA and age, SLEDAI, CRP, IgG, IgM or IgA. Furthermore, analysis of covariance demonstrated that anti-Sm (β=-0.218, P=0.004) and -U1RNP (β=0.177, P=0.008) autoantibodies were independent determinants of serum UA. The UA level is independently associated with the development of LN in SLE patients.
Rheumatology International 02/2010; 31(6):743-8. · 1.88 Impact Factor
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Clinical Chemistry and Laboratory Medicine 02/2009; 47(1):116-7. · 2.15 Impact Factor
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ABSTRACT: Monoclonal gammopathies are characterized by the presence of monoclonal immunoglobulin in patients with or without evidence of multiple myeloma (MM), macroglobulinemia, amyloidosis (AL), or a related plasma cell proliferative disorder. This study aims to evaluate laboratory diagnostic characters of monoclonal gammopathies and investigates the correlation between monoclonal gammopathies and transforming growth factor beta1 (TGFbeta1). Immunofixation electrophoresis (IFE), serum protein electrophoresis (SPE), nephelometry and urine light chain ELISA were used for laboratory identification of monoclonal immunoglobulins. Plasma TGFbeta1 was detected with double-antibodies ELISA. Lightcycler was used for single nucleotide polymorphism (SNP) analysis. Totally 2,007 cases of monoclonal immunoglobulin (M protein) were identified in 10,682 samples. The isotypes of M protein were IgG type 47.1%, IgA 23.0%, IgM 8.7%, IgD 5.3%, free light chain kappa 6.1%, lambda 9.8%. In reference to IFE, the coherency of diagnosis was serum light chain ratio (kappa/lambda ) 94.4%, quantitation of Igs 83%, light chain quantitation 80.9%, and urine light chain ratio (kappa/lambda) 58.0%. Plasma TGFbeta1 was elevated significantly compared to normal control. The allelic frequency of codon 10 (C>T) was neither associated with the existence of the M protein nor with the M protein isotype. Monoclonal gammopathies can be identified with the combination of IFE, SPE, Igs quantitation and urine light chain determination. Although TGFbeta1, an important cytokine in immune regulation, was elevated in monoclonal gammopathies, the SNPs in coding region of TGFbeta1 gene did not confer susceptibility to the development of monoclonal gammopathies in this study.
Cellular & molecular immunology 08/2008; 5(4):293-8. · 2.99 Impact Factor
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ABSTRACT: Apoptosis plays a pivotal role in portal tract damage of primary biliary cirrhosis (PBC). Tumour necrosis factor-related apoptosis inducing ligand (TRAIL) is an apoptotic inducer, and it has been reported that the expression of TRAIL receptors is up-regulated by increased bile acid level and the serum level of soluble TRAIL (sTRAIL) is elevated in PBC patients. In the present study, we investigated the association of TRAIL in peripheral blood with the pathogenesis of PBC and chronic hepatitis B. The expression levels of TRAIL mRNA and protein on leukocytes and sTRAIL in plasma from 27 patients with PBC, 25 with CHB and 30 healthy controls were determined respectively by real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-PCR), flow cytometry (FCM) and ELISA. The expression levels of TRAIL mRNA and protein on leukocytes and plasma sTRAIL were all up-regulated in the patients with PBC and CHB compared to controls. In the two diseased groups, TRAIL mRNA showed significant correlation of both membrane-bound TRAIL (mTRAIL) on monocytes and plasma sTRAIL. So did plasma TNF-alpha. In PBC patients, mTRAIL and sTRAIL correlated well with gamma-glutamyltransferase and alkaline phosphatase, but not with aspartate aminotransferase and alanine amino-transferase. The opposite case was found in CHB patients. These results suggested that both mTRAIL and sTRAIL might be involved in the development and progression of PBC and CHB in humans, but the mechanisms might be different.
Clinical and Experimental Medicine 04/2008; 8(1):1-7. · 1.58 Impact Factor
