Yanfang Jiang

High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis

This study aimed to examine the frequency of different subsets of circulating B and T follicular helper (Tfh) cells in patients with new‐onset rheumatoid arthritis (RA) and following standard therapies. Twenty‐five RA patients and 15 healthy controls (HC) were recruited for characterizing the frequency of CD27+, immunoglobulin (Ig)D+, CD86+, CD95+, Toll‐like receptor (TLR)‐9+ B cells and inducible T cell co‐stimulator (ICOS) and programmed death 1 (PD‐1)‐positive Tfh cells and the level of serum interleukin (IL)‐21. The potential correlation between the frequency of different subsets of B and Tfh cells and the values of clinical measures in RA patients was analysed. In comparison with HC, significantly higher percentages of circulating IgD+CD27−CD19+ naive B, CD86+CD19+ and CD95+CD19+ activated B, CD3+CD4+CXCR5+, CD3+CD4+CXCR5+ICOS+, CD3+CD4+CXCR5+PD‐1+ and CD3+CD4+CXCR5+ICOS+PD‐1+ Tfh cells but lower IgD+CD27+CD19+ preswitch memory B cells were detected, accompanied by significantly higher levels of serum IL‐21 in the RA patients. Furthermore, the percentages of CD95+ B cells were correlated positively with the frequency of PD‐1+ Tfh cells, but negatively with ICOS+ Tfh cells. The percentages of CD86+ B cells and ICOS+ Tfh cells were correlated positively with the values of disease activity score 28 (DAS28). Following the drug therapies for 1 month, the percentages of CD86+ B and PD‐1+ Tfh cells were reduced significantly in the drug‐responding patients. Our data suggest that activated B and Tfh cells may contribute to the pathogenesis of RA and the frequency of activated B and Tfh cells may be used as biomarkers for evaluating the therapeutic responses of individual patients with RA.

IL28B Genetic Variation Is Associated with Spontaneous Clearance of Hepatitis C Virus, Treatment Response, Serum IL-28B Levels in Chinese Population

Background The interleukin-28B gene (IL28B) locus has been associated with host resistance to hepatitis C virus (HCV) infection and response to PEG-IFN/RBV treatment in western populations. This study was to determine whether this gene variant is also associated with spontaneous clearance of HCV infection, treatment response and IL-28B protein production in Chinese patients. Methods We genotyped IL28B genetic variations (rs12980275, rs8103142, rs8099917 and rs12979860) by pyrosequencing DNA samples from cohorts consisting of 529 subjects with persistent HCV infection, 196 subjects who cleared the infection, 171 healthy individuals and 235 chronic HCV patients underwent IFN/RBV treatment. The expression of IL-28B were measured by ELISA and RT-PCR. Results We found that the four IL28B variants were in complete linkage disequilibrium (r2 = 0.97–0.98). The rs12979860 CC genotype was strongly associated with spontaneously HCV clearance and successful IFN/RBV treatment compared to the CT/TT. IL-28B levels in persistent HCV patients were significantly lower than subjects who spontaneously resolved HCV and healthy controls and were also associated with high levels of ALT (alanine aminotransferase) and AST (aspartate aminotransferase). IL-28B levels were also significantly lower in individuals carrying T alleles than CC homozygous. Conclusions Thus, the rs12979860-CC variant upstream of IL28B gene is associated with spontaneous clearance of HCV, susceptible to IFN/RBV treatment and increased IL-28B levels in this Chinese population.

High frequency of CD4+ CXCR5+ TFH cells in patients with immune-active chronic hepatitis B.

Background T follicular helper (TFH) cells are a special subpopulation of T helper cells and can regulate humoral immune responses. This study examined whether the frequency of CD4+CXCR5+ TFH cells could be associated with active immunity in chronic hepatitis B (CHB) patients. Methodology and Findings The frequencies of peripheral blood CD4+CXCR5+ TFH cells, inducible T cell costimulator (ICOS), and/or programmed death 1 (PD-1) positive CD4+CXCR5+ TFH cells in immune-active (IA), immune-tolerant (IT) CHB, and healthy controls (HC) were characterized by flow cytometry analysis. The effect of adevofir dipivoxil treatment on the frequency of CD4+CXCR5+ TFH cells, the concentrations of serum IL-2, IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-21, ALT, AST, HBsAg, HBsAb, HBeAg, HBeAb and HBV loads in IA patients were determined. The potential association of the frequency of CD4+CXCR5+ TFH cells with clinical measures was analyzed. In addition, the frequency of splenic and liver CD4+CXCR5+ TFH cells in HBV-transgenic mice was examined. We found that the frequency of CD4+CXCR5+ TFH cells in IA patients was significantly higher than that of IT patients and HC, and the percentages of CD4+CXCR5+ TFH in IA patients were positively correlated with AST. Furthermore, the percentages of ICOS+, PD-1+, and ICOS+PD-1+ in CD4+CXCR5+ TFH cells in CHB patients were significantly higher than that of HC. Treatment with adefovir dipivoxil reduced the frequency of CD4+CXCR5+ TFH, PD-1+CD4+CXCR5+ TFH cells and the concentrations of HBsAg and HBeAg, but increased the concentrations of HBsAb, HBeAb, IL-2 and IFN-γ in IA patients. Moreover, the frequency of splenic and liver CD4+CXCR5+ TFH cells in HBV-transgenic mice was higher than that of wild-type controls. Conclusions These data indicate that CD4+CXCR5+ TFH cells may participate in the HBV-related immune responses and that high frequency of CD4+CXCR5+ TFH cells may be a biomarker for the evaluation of active immune stage of CHB patients.

Expression and gene polymorphisms of interleukin 28B and hepatitis B virus infection in a Chinese Han population

Background: Recent genome‐wide association studies found that genetic polymorphisms near the IL28B gene is strongly associated with sustained viral response and spontaneous viral clearance in chronically infected hepatitis C patients.

Th1 and Th2 Immune Response in Chronic Hepatitis B Patients during a Long-Term Treatment with Adefovir Dipivoxil

Adefovir dipivoxil treatment has significantly improved the outcome of chronic hepatitis B virus (HBV) infection. However, it remains largely unknown how immune system responds to the treatment. Chronic HBV patients were treated with adefovir dipivoxil and examined for serum HBV DNA loads, cytokines, and T helper (Th1) and 2 (Th2) cytokine producing T cells during 104 weeks of the treatment. Th1/Th2 cytokines producing T cells were significantly lower in chronic HBV patients as compared to normal individuals. Adefovir dipivoxil treatment led to the increase of Th1/Th2 cytokines producing T cells and serum cytokine levels in association with the decline of HVB DNA load. In contrast, Th1/Th2 cytokines producing T cells remained lower in one patient detected with adefovir dipivoxil resistant HBV A181T/V mutation. This study has established inverse correlation of the increase of Th1/Th2 immunity and the decline of HBV DNA load in chronic HBV patients during adefovir dipivoxil treatment.

Plasma levels of IL-37 and correlation with TNF-α, IL-17A, and disease activity during DMARD treatment of rheumatoid arthritis.

The aim of this study was to assess the change of IL-37 concentrations in rheumatoid arthritis (RA) patients under Disease-modifying anti-rheumatic drug (DMARD) therapy, and to establish a correlation between Interleukin-37 and pro-inflammatory cytokines in plasma and disease activity. The plasma level of IL-37 was determined using ELISA in 50 newly diagnosed RA patients and 30 healthy controls (HC). Plasma levels of IL-17A, IL-6 and TNF-α were measured using flow a cytometric bead array assay. We found that the concentrations of IL-37, as well as IL-17A, IL-6 and TNF-α, were higher in plasma of RA patients compared to HCs. Compared to patients who did not respond to DMARD treatment, treatment of patients responsive to DMARDs resulted in down-regulation of IL-17A, IL-6 and TNF-α expression. The plasma level of the anti-inflammatory cytokine IL-37 was also decreased in drug responders after DMARD treatment. The plasma level of IL-37 in RA patients was positively correlated with pro-inflammatory cytokines (IL-17A, TNF-α) and disease activity (CRP, DAS28) in RA patients. IL-37 expression in RA and during DMARD treatment appears to be controlled by the level of pro-inflammatory cytokines. This results in a strong correlation between plasma levels of IL-37 and disease activity in RA patients.

Serum IL-33 Levels Are Associated with Liver Damage in Patients with Chronic Hepatitis B

This aim of this study was to assess the potential role of IL-33 in the pathogenic process of chronic hepatitis B (CHB). The levels of serum IL-33 and soluble ST2 (sST2) in CHB patients and healthy controls (HC) were determined using enzyme-linked-immunosorbent serologic assay, and the Th1 (IFN-γ, TNF-α, IL-2) and Th2 (IL-4, IL-6, IL-10) cytokines by cytometric bead array. It was found that the levels of serum IL-33 in CHB patients were significantly higher than that of HC at the base line, but decreased after treatment with adefovir dipivoxil for 12 weeks. The levels of serum sST2, as a decoy receptor of IL-33, were significantly higher in CHB patients than the HC. There was no correlation between the levels of serum sST2 and IL-33. The concentrations of serum Th1 (IFN-γ, IL-2) and Th2 (IL-6, IL-10) cytokines in CHB patients significantly increased after treatment compared to the baseline. These results suggest that IL-33 is involved in the pathogenesis of CHB and that adefovir dipivoxil therapy can attenuate the production of IL-33 in patients with CHB.

MicroRNA-424 Is Down-Regulated in Hepatocellular Carcinoma and Suppresses Cell Migration and Invasion through c-Myb

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are important regulators of multiple cellular processes, and the aberrant miRNAs expressions have been observed in different types of cancer including HCC. Their pathysiologic role and their relevance to tumorigenesis are still largely unknown. In this study, we demonstrated the down-regulation of miR-424 in HCC cell lines and tissues by quantitative RT-PCR analyses. Overexpression of miR-424 reduced the HCC cell prolifetation, migration, and invasion. Conversely, inhibiton of miR-424 expression significantly accelerated the cell proliferation, migration, and invasion. In addition, we further identified c-Myb as a functional downstream target of miR-424 by directly targeting the 3′UTR of c-Myb. Furthermore, overexpression of c-Myb impaired miR-424-induced inhibition of proliferation and invasion in HCC cells. Our results demonstrated that miR-424 was involved in tumorigenesis of HCC at least in part by suppression of c-Myb.

A high frequency of circulating th22 and th17 cells in patients with new onset graves' disease.

T-helper (Th) 22 and Th17 cells are involved in the pathogenesis of autoimmune diseases. However, their roles in the pathogenesis of Graves’disease (GD) are unclear. This study is aimed at examining the frequency of peripheral blood Th22, Th17, and Th1 cells and the levels of plasma IL-22, IL-17, and IFN-γ in patients with GD. A total of 27 patients with new onset GD and 27 gender- and age-matched healthy controls (HC) were examined for the frequency of peripheral blood Th22, Th17, and IFN-γ cells by flow cytometry. The concentrations of plasma IL-22, IL-17, and IFN-γ were examined by enzyme-linked immunosorbent assay. The levels of serum TSHR antibodies (A-TSHR), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) were examined by radioimmunoassay and chemiluminescent assay, respectively. The levels of serum TSAb were examined by enzyme-linked immunosorbent assay. In comparison with those in the HC, significantly elevated percentages of Th22 and Th17 cells, but not Th1 cells, and increased levels of plasma IL-22 and IL-17, but not IFN-γ, were detected in GD patients (P<0.0001, for both). The percentages of both Th22 and Th17 cells and the levels of plasma IL-22 and IL-17 were correlated positively with the levels of serum TSAb in GD patients (r = 0.7944, P<0.0001; r = 0.8110, P<0.0001; r = 0.7101, p<0.0001; r = 0.7407, p<0.0001, respectively). Th22 and Th17 cells may contribute to the pathogenesis of GD.

Elevated Levels of Cerebrospinal Fluid and Plasma Interleukin-37 in Patients with Guillain-Barré Syndrome

Aims. Interleukin-37 (IL-37) is an anti-inflammatory cytokine. This study aims to investigate the concentrations of plasma and cerebrospinal fluid (CSF) IL-37 in patients with Guillain-Barré Syndrome (GBS). Methods. The levels of plasma and CSF IL-37, IL-17A, IFN-γ, and TNF-α in 25 GBS patients and 20 healthy controls (HC) were determined by enzyme-linked immunoabsorbent assay and flow cytometric bead array assay, respectively. The values of clinical parameters in the patients were also measured. Results. The concentrations of plasma IL-37, IL-17A, IFN-γ, and TNF-α and CSF IL-37 and IL-17A in patients at the acute phase of GBS were significantly higher than those in the HC. The levels of plasma IL-37, IL-17A, IFN-γ, and TNF-α were positively correlated in those patients, and the levels of CSF IL-37 and IL-17A as well as the levels of plasma TNF-α were correlated positively with the GBS disability scale scores (GDSs) in those patients. Treatment with intravenous immunoglobulin significantly reduced the levels of plasma IL-37, IL-17A, IFN-γ, and TNF-α in the drug-responding patients. Conclusions. Our findings indicate higher levels of plasma and CSF IL-37 and IL-17A and other proinflammatory cytokines in patients with GBS.