Twenty four-week peginterferon plus ribavirin after interferon-β induction for genotype 1b chronic hepatitis C

AIM:To investigate the possibility of shortening the duration of peginterferon(Peg-IFN)plus ribavirin(RBV) combination therapy by incorporating interferon-β (IFN-β)induction therapy. METHODS:A one treatment arm,cohort prospective study was conducted on seventy one patients.The patients were Japanese adults with genotype 1b chronic hepatitis C,HCV-RNA levels of≥5.0 Log IU/mL or 100 KIU/mL,and platelet counts of≥90 000/μL.The treatment regimen consisted of a 2 wk course of twicedaily administration of IFN-βfollowed by 24 wk PegIFN plus RBV combination therapy.We prolonged the duration of the Peg-IFN plus RBV therapy to 48 wk if the patient requested it. RESULTS:The patients,including 44%males,were characterized by an median age of 63 years(range: 32-78 years),an median platelet count of 13.9(range: 9.1-30.6)×10 4 /μL,62%IFN-na?ve,and median HCV- RNA of 6.1(range:5.1-7.2)Log IU/mL.The sustained virologic response(SVR)rates were 34%(Peg-IFN:1-24 wk,n=61,95%confidence interval(CI): 24%-47%)and 55%(Peg-IFN:20-24 wk,n=31,95% CI:38%-71%,P<0.001;vs Peg-IFN:1-19 wk).TheSVR rate when the administration was discontinued early was 13%(Peg-IFN:1-19 wk,n=30,95%CI: 5%-30%),and that when the administration was prolonged was 50%(Peg-IFN:25-48 wk,n=10,95% CI:24%-76%,P<0.05;vs Peg-IFN:1-19 wk).In the patients who received 20-24 wk of Peg-IFN plus RBV,only the higher platelet count(≥130 000/μL) was significantly correlated with the SVR(odds ratio: 11.680,95%CI:2.3064-79.474,P=0.0024).In 45% (14/31)of the patients with a higher platelet count (≥130000/μL)before therapy,the HCV-RNA level decreased to below 3.3 Log IU/mL at the completion of IFN-β,and their SVR rate was 93%(13/14)after 20-24 wk administration of Peg-IFN plus RBV. CONCLUSION:These results suggest the possibilities of shortening the duration of Peg-IFN plus RBV combination therapy by actively reducing HCV-RNA levels using the IFN-βinduction regimen.

Construction of retroviral vectors to induce a strong expression of human interferon-β gene in human hepatoma cells

Establishing the hepatoma cell-specific expression of human interferon gene mediated by retroviral vectors. Methods: Human interferon-β complementary DNA (IFN-β cDNA) was inserted into polylinker site of pMNSM retroviral vector to construct recombinant retroviral vector pMNSIFNB, where the transcription of IFN-β gene was driven by SV40 early region promoter, and MNAIFNB, where the transcription of IFN-β gene was driven by SV40 early region promoter regulated by α-fetoprotein enhancer. The retroviral constructs were respectively introduced into PA317 amphotropic packaging cells by means of lipofectamine mediated gene transfer procedure. The plasmids transfection efficiency was among (4-25)ｘ103 colonies/μg DNA/106 PA317 cells. The retrovirus infection efficiency was among (4. 5-500)ｘ104 Colony Forming Units (CFU)/ml. The recombinant retroviruses were used to infect human hepatoma cells, renal cell carcinoma cells and melanoma cell lines in the presence of 4 μg/ml polybrene. Results: Dot hybridization of total RNA from the neomycin resistant colonies and interferon expression assay indicated that human α-fetoprotein enhancer induced efficient and specific transcription and expression of IFN-β gene driven by the promoter of different origin in human hepatoma cells by which α-fetoprotein was highly produced. Conclusion: Cis-active element of α-fetoprotein gene can drive IFN-β gene specifically expressed in human hepatoma cells, which presents some valuable materials for the hepatoma-specific immune gene therapy.

Interferon-lambda:New functions on intestinal symptoms in COVID-19

The tremendous public health and economic impact of coronavirus disease 2019(COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2), has become a huge challenge globally. There is increasing evidence that SARS-CoV-2 induces intestinal infections. Type Ⅲ interferon(IFN-λ) has an antiviral role in intestinal infection, with focused, long-lasting, and non-inflammatory characteristics. This review presents a summary of the structure of SARSCoV-2, including its invasion and immune escape mechanisms. Emphasis was placed on the gastrointestinal impact of SARS-CoV-2, including changes to the intestinal microbiome, activation of immune cells, and inflammatory responses.We also describe the comprehensive functions of IFN-λ in anti-enteric SARS-CoV-2 infection, and discuss the potential application of IFN-λ as a therapeutic agent for COVID-19 with intestinal symptoms.

Construction of Fluorescence Sensing Platform on the Basis of Carbon Nitride Nanosheet for the Detection of Interferon-γ

Purpose: Interferon-γ (INF-γ) is a cytokine that participates in the immune reaction of the body. Its level of secretion can reflect the immune response condition after the body is infected by pathogens, which is a significant indication of clinically-related diseases. Therefore, it is of great significance in application to develop a fluorescence biosensor to inspect INF-γ with rapidness, high sensitivity and high practicability. Method: The fluorescence sensor is made on the basis of the two-dimensional nano-material namely Carbon Nitride Nanosheet (CNNS) and the Aptamer probe to identify INF-γ (Apt&reg;INF-γ). CNNS can quickly quench the Cy5 fluorescent dye modified on the Apt&reg;INF-γ probe due to the Photoinduced Electron Transfer (PET), but when the INF-γ exists, Apt&reg;INF-γ specifically identifies and combines it. The complex of Apt&reg;INF-γ and INF-γ is away from CNNS, which can effectively block the fluorescent signal of Apt?INF-γ being quenched by CNNS. Result: The sensitive detection of IFN-γ protein can be achieved through the application of CNNS/Apt&reg;INF-γ fluorescence sensing platform. In this method, the intensity of the fluorescent signal is positively correlated with the concentration of IFN-γ, of which the liner response range is 0.5 - 100 ng/mL and the limit of detection is 0.303 ng/mL. In addition, this fluorescence sensing platform has the advantages of high specificity, simple operation and low costs. It can inspect the content of IFN-γ in clinical serum samples without interference. The actual recovery rate of serum samples is 97.11% - 106.96%. Conclusion: Therefore, the CNNS/Apt&reg;INF-γ sensing platform is expected to be implemented in the actual clinical detection, also conducive to developing a universal fluorescence biosensor to inspect other target materials.

Development and validation of a prognostic indicator for thyroid carcinoma based on interferon-γ-related gene analysis

Background:Women are mostly affected by thyroid carcinoma(THCA),an endocrine system cancer.However,the biomarkers of interferon-gamma(IFN-γ)in THCA have not been identified,so this study aimed to investigate whether IFN-γ-related genes could predict the overall prognosis of THCA patients.Methods:Transcriptome-related expression data were obtained from The Cancer Genome Atlas database.Differential expression of IFN-γ-responsive genes(DE-IFN-γ)between THCA and normal samples was determined based on the“limma”package in R.The prognostic value of the model was determined by least absolute shrinkage and selection operator,univariate Cox,and multivariate Cox analyses,as well as Kaplan-Meier curves.A nomogram was created to predict the THCA survival probabilities by combining clinicopathological features and prognostic genetic features.High-risk and low-risk groups were examined THCA-related pathways using gene set enrichment analysis.Correlations between the two groups with different scores and the immune microenvironment and immunotherapy were also explored.Finally,we verified the expression levels using real-time PCR.Results:From 48 DE-IFN-γ,4 DE-IFN-γ(METTL7B,VAMP8,CFB,IFIT3)associated with good prognosis were selected by least absolute shrinkage and selection operator and Cox co-screening.Based on these four genes,THCA patients were divided into two groups,with the high-risk group having a poorer overall survival rate.The risk score,age,and staging were identified as independent prognostic factors.The low-scoring group had significantly enriched 13 signaling pathways,according to gene set enrichment analysis.Meanwhile,the two groups delineated according to the risk score differed in terms of the immune microenvironment and immune checkpoints.Finally,our real-time PCR results corroborated previous hypotheses.Conclusion:Researchers identified four DE-IFN-γbiomarker genes with promising prognostic value for THCA patients,which may help guide immunotherapy preference.Moreover,it may subsequently influence our THCA treatment decisions.

Therapeutic effect of Qinghuayin(清化饮)against chronic atrophic gastritis through the inhibition of toll or interleukin-1 receptor domain-containing adaptor inducing interferon-β signaling pathway

OBJECTIVE:To examine the efficacy of Qinghuayin(清化饮,QHY)in rat chronic atrophic gastritis(CAG)models and explored the molecular mechanism of QHY in treating CAG.METHODS:In total,65 Wistar rats were randomly divided into the control(n=10)and CAG groups(n=55).CAG model rats were further divided into five groups:model(n=10),vitacoenzyme(n=10),low-dose QHY(n=10),medium-dose QHY(n=10),and high-dose QHY groups(n=10).We analyzed histopathological changes using hematoxylin and eosin staining and measured interleukin(IL)-6 and IL-8 levels in serum using enzyme-linked immunosorbent assay(ELISA)(Boster Bio,Pleasanton,USA).In addition,gastrin(GAS),pepsinogen I(PGI),and PGII expressions were evaluated using ELISA.The protein and m RNA expression of toll-like receptor 4(TLR4)and toll or interleukin-1 receptor domaincontaining adaptor inducing interferon-β(TRIF)was detected by Western blotting and quantitative reverse transcription-polymerase chain reaction,respectively.RESULTS:Our results revealed that histopathological changes in CAG model rates could be restored by low-,medium-,and high-dose QHY.The changes in GAS and PGI/II expression demonstrated that QHY improved CAG.Serum IL-6 and IL-levels were decreased by QHY administration.TLR4 and TRIF were upregulated at the m RNA and protein levels in the model group but downregulated by QHY administration.CONCLUSION:We concluded that QHY could effectively improve the histopathological changes of the gastric mucosa induced by CAG in rats.The therapeutic mechanism of QHY may be related to inhibition of the inflammatory factors IL-6 and IL-8 and suppression of TLR4/TRIF m RNA and protein expression.

肺腺癌中医证型与诱导痰TGF-β、IFN-γ、MMP-9的关系

目的观察肺腺癌中医证型与诱导痰转化生长因子(TGF)-β、干扰素(IFN)-γ、基质金属蛋白酶9(MMP-9)的关系。方法选取2020年1月至2023年1月临泉县人民医院收治的80例肺腺癌患者作为研究组,并根据研究组中医症型将其分为脾肾阳虚型(A组),气阴两虚型(B组)以及肺脾气虚型(C组),另外选取同期体检健康人群80名作为对照组,比较各组诱导痰TGF-β、IFN-γ、MMP-9水平。结果80例肺腺癌患者中,脾肾阳虚型患者28例(35.00%),气阴两虚型患者26例(32.50%),肺脾气虚型患者26例(32.50%)。研究组患者诱导痰TGF-β、MMP-9水平高于对照组,差异有统计学意义(t=5.793、20.727,P<0.05),诱导痰IFN-γ水平低于对照组,差异有统计学意义(t=6.511,P<0.05)。A组患者诱导痰TGF-β、MMP-9水平高于B组、C组,差异有统计学意义(t=3.704、3.859、5.948、6.290,P<0.05),诱导痰IFN-γ水平及KPS评分低于B组、C组,差异有统计学意义(t=9.391、8.982、2.748、2.282,P<0.05)。B组与C组患者诱导痰TGF-β、IFN-γ、MMP-9水平及KPS评分之间的差异无统计学意义(t=0.269、0.808、0.421、0.376,P>0.05)。pearson相关性结果显示,诱导痰TGF-β、MMP-9水平与KPS评分成负相关(P<0.05),IFN-γ水平与KPS评分成正相关(P<0.05)。结论与气阴两虚型及肺脾气虚型肺腺癌患者相比,脾肾阳虚型患者诱导痰TGF-β及MMP-9水平较高,IFN-γ水平较低,且三者均与KPS评分具有相关性,可作为肺腺癌中医辨证的辅助指标。

Preliminary results of Thymosin-a1 versus interferon-α treatment in patients with HBeAg negative and serum HBV DNA positive chronic hepatitis B

INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .

Anti Cervix Cancer Activity of Co-immobilized Tumor Necrosis Factor-α and Interferon-γ

Tumor necrosis factor α （TNF-α） and interferon-γ （IFN-γ） are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and IFN-γ. The infrared （IR） spectra of these products showed the characteristic absorption of an azido group at 2127 cm^-1. By photo-immobilization, this modified TNF-α and IFN-γ were immobilized on polystyrene membranes for cell culture to prepare biomaterials. The micro-morphology of photoactive cytokines was observed with a scanning electron microscope （SEM）. The inhibitory effect on growth of Hela cells and inducing apoptosis activity of these two cytokines were analyzed by growth curve, transmission electron microscope （TEM） and fluorescence active cell sorter （FACS）. The results showed that co-immobilization of IFN-γ and TNF-α had significant inhibitory effect on growth of Hela cells, inhibitory rate up to 82%, and IFN-γ had obviously synergistic action.

Anti-rods/rings autoantibody generation in hepatitis Cpatients during interferon-α/ribavirin therapy

Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α(IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies(ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings(RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings(antiRR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2(IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon.

Precise prediction model and simplified scoring system for sustained combined response to interferon-α

AIM:To establish a predictive algorithm which may serve for selecting optimal candidates for interferon-α(IFN-α) treatment.METHODS:A total of 474 IFN-α treated hepatitis B virus e antigen(HBeAg)-positive patients were enrolled in the present study.The patients' baseline characteristics,such as age,gender,blood tests,activity grading(G) of intrahepatic inflammation,score(S) of liver fibrosis,hepatitis B virus(HBV) DNA and genotype were evaluated;therapy duration and response of each patient at the 24th wk after cessation of IFN-α treatment were also recorded.A predictive algorithm and scoring system for a sustained combined response(CR) to IFN-α therapy were established.About 10% of the patients were randomly drawn as the test set.Responses to IFN-α therapy were divided into CR,partial response(PR) and non-response(NR).The mixed set of PR and NR was recorded as PR+NR.RESULTS:Stratified by therapy duration,the most significant baseline predictive factors were alanine aminotransferase(ALT),HBV DNA level,aspartate aminotransferase(AST),HBV genotype,S,G,age and gender.According to the established model,the accuracies for sustained CR and PR+NR,respectively,were 86.4% and 93.0% for the training set,81.5% and 91.0% for the test set.For the scoring system,the sensitivity and specificity were 78.8% and 80.6%,respectively.There were positive correlations between ALT and AST,and G and S,respectively.CONCLUSION:With these models,practitioners may be able to propose individualized decisions that have an integrated foundation on both evidence-based medicine and personal characteristics.

Clinical Value of Vascular Endothelial Growth Factor Combined with Interferon-γ in Diagnosing Malignant Pleural Effusion and Tuberculous Pleural Effusion

In order to investigate the clinical value of vascular endothelial growth factor （VEGF） combined with interferon-γ （IFN-γ） in diagnosing malignant pleural effusion and tuberculous pleural effusion, 42 cases of malignant pleural effusion and 45 cases of tuberculous pleural effusion in Tongji Hospital, from March 2004 to May 2005, were included, The carcinoembryonic antigen （CEA）, VEGF and IFN-γ levels of pleural effusion were detected by using ELISA, and adenosine deaminase （ADA） activity was determined by using enzyme kinetic analytical method. The sensitivity, specificity, accuracy and area under the curve （AUCR^ROC） of CEA and VEGF, VEGF/IFN-γ ratio, ADA and IFN-γ were measured by receiver operating characteristic curve （ROC）, The results showed that CEA, VEGF levels and VEGF/IFN-γ ratio were significantly higher and the ADA and IFN-γ levels were significantly lower in malignant group than those in tuberculous group （P〈0,01）, The sensitivity, specificity, accuracy and AUCR^ROC of VEGF/IFN-γ ratio （88,7%, 99,8%, 94,4%, 0.96 respectively） were higher than those of CEA （67.8%, 96.1%, 82,4%, 0.78 respectively） and VEGF （81,5%, 84,3%, 82.9%, 0.79 respectively）. The sensitivity, specificity, accuracy and AUCR^ROC of IFN-γ （85.7%, 96,4%, 90.9%, 0.94 respectively） were higher than those of ADA （80,2%, 87,6%, 83.8%, 0,81 respectively）. It was concluded that VEGF/IFN-γ ratio and IFN-γ could be used as valuable parameters for the differential diagnosis of malignant pleural effusion and tuberculous pleural effusion.

Interferon-α induced severe thrombocytopenia:A case report and review of the literature

We report a case of severe thrombocytopenia following pegylated interferon-α 2a(Peg-IFN-α 2a)treatment of hepatitis C virus infection and summarize the clinical characteristics of 16 cases of IFN-α induced severe thrombocytopenia and its immune-mediated mechanism.Discontinuation of IFN-α and early administration of immunosuppressants are the effective therapy for IFN-αinduced severe thrombocytopenia.

IFIT1 polymorphisms predict interferon-α treatment efficiency for hepatitis B virus infection

AIM To investigate the association between interferoninduced protein with tetratricopeptide repeats 1(IFIT1) polymorphisms and interferon-α(IFNα) treatment efficiency among Chinese hepatitis B virus(HBV) infection patients.METHODS Two hundred and twenty five newly diagnosed chronichepatitis B(CHB) patients were enrolled in the study. All of these patients received IFNα treatment for a course of 48 wk, and were followed up for 24 wk after the treatment was end. Clinical information about virological response, hepatitis B e antigen(HBe Ag) seroconversion rate and combined response at the end of the treatment, as well as the sustained response by the time of following up 24 wk after the treatment, was collected. Four tag-single nucleotide polymorphisms(SNPs) of IFIT1 were selected and assessed for their association with these clinical outcomes.RESULTS At the end of the treatment, HBe Ag seroconversion was observed in 27.1% patients. Thirty-six point nine percent patients achieved virological response, and 15.6% patients exhibited combined response. Sustained response was obtained in 26.2% patients. The main HBV genotype of the study was genotype B. Patients who infected with HBV genotype B or C showed better treatment efficiency, no matter which clinical outcome was considered. Among the four SNPs assessed, rs303218(A > G) was found to be significantly associated with the end point virological response when assuming additive model [OR = 0.64(95%CI: 0.42-0.96), P = 0.032]. Patients who carried rs303218 GG genotype had a rather higher rate of achieving virological response(response rate: 52%, OR = 0.40, 95%CI: 0.18-0.91; P = 0.028) when compared to those had AA genotype(response rate: 27%). The most significant interaction was observed in patients who had relative lower baseline aspartate transaminase. No association between SNPs and HBe Ag seroconversion, combined response or sustained response was observed.CONCLUSION IFIT1 involves in the regulation of IFNα treatment for CHB and its polymorphism rs303218 can predict the end point virological response. The finding requires further validation.

Interferon-γ: Promising therapeutic target in atherosclerosis

Atherosclerosis is a chronic inflammatory disorder of the vasculature and is the primary cause of cardiovascular disease(CVD). CVD is currently the world's leading cause of death and the numbers are predicted to rise further because of a global increase in risk factors such as diabetes and obesity. Current therapies such as statins have had a major impact in reducing mortality from CVD. However, there is a marked residual CVD risk in patients on statin therapy. It is therefore important to understand the molecular basis of this disease in detail and to develop alternative novel therapeutics. Interferon-γ(IFN-γ) is a pro-inflammatory cytokine that is often regarded as a master regulator of atherosclerosis development. IFN-γ is able to influence several key steps during atherosclerosis development, including pro-inflammatory gene expression, the recruitment of monocytes from the blood to the activated arterial endothelium and plaque stability. This central role of IFN-γ makes it a promising therapeutic target. The purpose of this editorial is to describe the key role IFN-γ plays during atherosclerosis development, as well as discuss potential strategies to target it therapeutically.

Effect of oxymatrine on interferon-gamma and tumor necrosis factor-alpha serum levels in an experimental rat model of autoimmune encephalomyelitis

BACKGROUND： Studies have demonstrated that experimental autoimmune encephalomyelitis （EAE） onset correlates with increased interferon-v （IFN-γ） and tumor necrosis factor-α （TNF-α） expression. Oxymatrine （OM） has been shown to inhibit autoimmune responses, but there are no reports showing that it could prevent the development of EAE. OBJECTIVE： To observe the effect of OM on serum levels of IFN-γ and TNF-α in a rat model of EAE.DESIGN, TIME AND SETTING： A randomized, controlled, animal study was performed at the Experimental Animal Center of Henan Academy of Chinese Medicine and at the Key Disciplines Laboratory Clinical Medicine of Henan Province between July and December 2008. MATERIALS： OM was purchased from Chia-tai Tianqing Pharmaceutical, China; complete Freund＇s adjuvant was purchased from Sigma, USA. METHODS： Forty female Wistar rats were randomly assigned to four groups： EAE model （M）, low-dose OM treatment （OM-L）, high-dose OM treatment （OM-H）, and normal control （N, no immunization）, with 10 rats in each group. EAE was established in the M, OM-L, and OM-H groups following immunization with Guinea pig spinal cord homogenate and complete Freund＇s adjuvant. The M and N groups were intraperitoneally injected with normal saline （6.7 mL/kg per day）, the OM-L group received an intraperitoneal injection of OM （100 mg/kg per day）, and the OM-H group received OM （150 mg/kg per day）. MAIN OUTCOME MEASURES： At 16 days after immunization, the degree of histopathological changes in the spinal cord was assessed by hematoxylin-eosin stanining. Enzyme-linked immunosorbent assay was used to detect serum levels of IFN-γ, and radioimmunoassay was utilized to determine serum TNF-α level. Neurological scores were measured on a daily basis according to a 0-5 scale. RESULTS： Daily injections of OM, both high and low doses, resulted in decreased neurological scores in EAE rats （P〈0.01）, as well as reduced cellular infiltration in the spinal cord and decreased levels of serum IFN-γ and TNF-α （P〈 0.01）. CONCLUSION： OM reduced the onset and severity of EAE, which correlated with decreased IFN-γ and TNF-α expression.

Failure of interferon-γ pre-treated mesenchymal stem cell treatment in a patient with crohn's disease

Mesenchymal stem cells(MSC) are cells of stromal origin which exhibit unlimited self-renewal capacity and pluripotency in vitro.It has recently been observed that MSC may also exert a profound immunosuppressive and anti-inflammatory effect both in vitro and in vivo with consequent potential use in autoimmune disorders.We present the case of a patient suffering from childhood-onset, multidrug resistant and steroiddependent Crohn's disease who underwent systemic infusions of MSC, which led to a temporary reduction in CCR4, CCR7 and CXCR4 expression by T-cells, and a temporary decrease in switched memory B-cells, In addition, following MSC infusion, lower doses of steroids were needed to inhibit proliferation of the patient's peripheral blood mononuclear cells.Despite these changes, no significant clinical benefit was observed, and the patient required rescue therapy with infliximab and subsequent autologous hematopoietic stem cell transplantation.The results of biological and in vitro observations after MSC use and the clinical effects of infusion are discussed, and a brief description is provided of previous data on MSC-based therapy in autoimmune disorders.

Hepatitis C virus genotypes, HLA-DRB alleles and their response to interferon-α and ribavirin in patients with chronic hepatitis C

BACKGROUND: Hepatitis C virus (HCV) is a worldwide common disease. Some predictive factors influencing the response to interferon alpha (IFN-α) therapy have been identified, but the conclusions differ in various counties and areas. The aim of this study was to study the associa- tions between HCV genotypes, HLA-DRB alleles and their response to IFN-α and ribavirin in Chinese patients with chronic hepatitis C in Northeast China. METHODS: HCV genotypes of 113 patients with HCV were investigated. Gene chips were used to analyze the fre- quency of HLA-DRB in 25 of these patients and their re- sponse to IFN-α and ribavirin. The associations of HCV genotypes, HLA-DRB alleles and their response to IFN-α and ribavirin were also studied. RESULTS: The response rates differed in several types of HCV, with HCV 2b being the highest (57.78% ), HCV 1a and 2a lower (46.15% and 47.62% ) and HCV 1b the low- est (11.76% ). The response rates to IFN-α and ribavirin in patients with DRB1 07 were higher than those with DRB1 04. Sex, HCV type and HLA-DRB were all related to the response. Most female patients with HCV 2b and HLA- DRB1 07 presented complete response, whereas male pa- tients with HCV 1b and HLA-DRB1 04 usually demon- strated no response. DRB1 07 allele and HCV 2b were the factors closely related to the response. CONCLUSIONS: The response rate of HCV 1b may be the lowest even IFN-α and ribavirin are combined in treat- ment. Not only virus but also the host plays an important role in anti-virus therapy. Thus, it is necessary to adjust the host's immune status to accelerate the clearance of HCV.

Heterogeneity of immune control in chronic hepatitis B virus infection:Clinical implications on immunity with interferon-αtreatment and retreatment

Hepatitis B virus(HBV)infection is a global public health issue.Interferon-α(IFN-α)treatment has been used to treat hepatitis B for over 20 years,but fewer than 5%of Asians receiving IFN-αtreatment achieve functional cure.Thus,IFN-αretreatment has been introduced to enhance antiviral function.In recent years,immune-related studies have found that the complex interactions between immune cells and cytokines could modulate immune response networks,including both innate and adaptive immunity,triggering immune responses that control HBV replication.However,heterogeneity of the immune system to control HBV infection,particularly HBV-specific CD8^(+)T cell heterogeneity,has consequential effects on T cell-based immunotherapy for treating HBV infection.Altogether,the host’s genetic variants,negative-feedback regulators and HBV components affecting the immune system's ability to control HBV.In this study,we reviewed the literature on potential immune mechanisms affecting the immune control of HBV and the clinical effects of IFN-αtreatment and retreatment.