8 research outputs found
A matched cross-sectional study of the association between circulating tissue factor activity, immune activation and advanced liver fibrosis in hepatitis C infection
Abstract Background Tissue factor (TF) is a protein that mediates the initiation of the coagulation cascade. TF expression is increased in patients with poorly-controlled HIV, and may be associated with increased immune activation that leads to cardiovascular morbidity. The role of TF in immune activation in liver disease in hepatitis C virus (HCV)-monoinfection and HIV/HCV-coinfection has not been explored. Methods Fifty-nine patients were stratified: A) HIV-monoinfection (Nβ=β15), B) HCV-monoinfection with chronic hepatitis C (CHC) (Nβ=β15), C) HIV/HCV-coinfection with CHC (Nβ=β14), and D) HIV/HCV-seropositive with cleared-HCV (Nβ=β15). All HIV+ patients had undetectable HIV viremia. Whole blood was collected for CD4/CD8 immune activation markers by flow cytometry and plasma was assayed for microparticle TF (MPTF) activity. Subjects underwent transient elastography (TE) to stage liver fibrosis. Undetectable versus detectable MPTF was compared across strata using Fisher's Exact test. Results MPTF activity was more frequently detected among patients with HCV-monoinfection (40%), compared to HIV-monoinfection and HIV/HCV-seropositive with cleared HCV (7%) and HIV/HCV-coinfection with CHC (14%) (pβ=β0.02). Mean TE-derived liver stiffness score in kPa was higher in patients with detectable MPTF (12.4βΒ±β8.5) than those with undetectable MPTF (6.4βΒ±β3.0) (pβ=β0.01). Mean CD4β+βHLADR+ and CD4β+βCD38-HLADR+ expression were higher in those with detectable MPTF (44βΒ±β9.8% and 38βΒ±β8.7%, respectively) than those with undetectable MPTF (36βΒ±β11% and 31βΒ±β10.4% respectively) (pβ=β0.05 and 0.04 respectively). Conclusions HCV-monoinfection and HIV/HCV-coinfection with CHC were associated with MPTF activity. MPTF activity is also associated with advanced liver fibrosis and with CD4β+βHLADR+ immune activation
Multiplex Immunoassay of Lower Genital Tract Mucosal Fluid from Women Attending an Urban STD Clinic Shows Broadly Increased IL1Γ and Lactoferrin
BACKGROUND: More than one million new cases of sexually transmitted diseases (STDs) occur each day. The immune responses and inflammation induced by STDs and other frequent non-STD microbial colonizations (i.e. Candida and bacterial vaginosis) can have serious pathologic consequences in women including adverse pregnancy outcomes, infertility and increased susceptibility to infection by other pathogens. Understanding the types of immune mediators that are elicited in the lower genital tract by these infections/colonizations can give important insights into the innate and adaptive immune pathways that are activated and lead to strategies for preventing pathologic effects. METHODOLOGY/PRINCIPAL FINDINGS: 32 immune mediators were measured by multiplexed immunoassays to assess the immune environment of the lower genital tract mucosa in 84 women attending an urban STD clinic. IL-3, IL-1Γ, VEGF, angiogenin, IL-8, Γ2Defensin and Γ3Defensin were detected in all subjects, Interferon-Ξ± was detected in none, while the remaining mediators were detected in 40% to 93% of subjects. Angiogenin, VEGF, FGF, IL-9, IL-7, lymphotoxin-Ξ± and IL-3 had not been previously reported in genital mucosal fluid from women. Strong correlations were observed between levels of TNF-Ξ±, IL-1Γ and IL-6, between chemokines IP-10 and MIG and between myeloperoxidase, IL-8 and G-CSF. Samples from women with any STD/colonization had significantly higher levels of IL-8, IL-3, IL-7, IL-1Γ, lactoferrin and myeloperoxidase. IL-1Γ and lactoferrin were significantly increased in gonorrhea, Chlamydia, cervicitis, bacterial vaginosis and trichomoniasis. CONCLUSIONS/SIGNIFICANCE: These studies show that mucosal fluid in general appears to be an environment that is rich in immune mediators. Importantly, IL-1Γ and lactoferrin are biomarkers for STDs/colonizations providing insights into immune responses and pathogenesis at this mucosal site
Relationships between STDs/Conditions and Immune Mediators.
<p>Levels in pg/ml except that HBD2, MPO, HBD3 and Lactoferrin are in
ng/ml. Any STD includes BV and Candida. Only variables with
p-value<0.05 have OR, 95% confidence interval and p-value
shown. The p-values are calculated based on Fisher exact test and
the odds ratios are calculated with correction, i.e., by adding 0.5
to counts if there were zero counts. Only two variables are selected
in the final model.</p><p>*Number missing in parenthesis.</p
Levels of Immune Mediators in CVL.
<p>Table is arranged from lowest to highest median values. ND: Not
Detectable; Mean and SD (Standard Deviation) are computed for the
detectable.</p><p>The total sample size:
N<sub>0</sub>+N<sub>1</sub>+N<sub>2</sub>β=β84.</p><p>*Levels in pg/ml except that HBD2, MPO, HBD3 and Lactoferrin are
in ng/ml.</p
Associations Between Mediators with Pearson Correlation Coefficients >0.7.
<p>The statistic is the correlation coefficient. Correlation
coefficients smaller than 0.7 are suppressed. All displayed
correlation coefficients have p-values smaller than 0.0001 in
testing the hypothesis of no correlation.</p
Heat map of cytokine levels.
<p>The heat map was generated using the web-based program Matrix2png <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019560#pone.0019560-Pavlidis1" target="_blank">[34]</a>
that displays microarray data visually (<a href="http://www.bioinformatics.ubc.ca/matrix2png/" target="_blank">http://www.bioinformatics.ubc.ca/matrix2png/</a>). The mean
for each row of cytokine values is 0 with red representing values
greater than 0, green lower than 0 and black 0.</p
A matched cross-sectional study of the association between circulating tissue factor activity, immune activation and advanced liver fibrosis in hepatitis C infection
Abstract Background Tissue factor (TF) is a protein that mediates the initiation of the coagulation cascade. TF expression is increased in patients with poorly-controlled HIV, and may be associated with increased immune activation that leads to cardiovascular morbidity. The role of TF in immune activation in liver disease in hepatitis C virus (HCV)-monoinfection and HIV/HCV-coinfection has not been explored. Methods Fifty-nine patients were stratified: A) HIV-monoinfection (Nβ=β15), B) HCV-monoinfection with chronic hepatitis C (CHC) (Nβ=β15), C) HIV/HCV-coinfection with CHC (Nβ=β14), and D) HIV/HCV-seropositive with cleared-HCV (Nβ=β15). All HIV+ patients had undetectable HIV viremia. Whole blood was collected for CD4/CD8 immune activation markers by flow cytometry and plasma was assayed for microparticle TF (MPTF) activity. Subjects underwent transient elastography (TE) to stage liver fibrosis. Undetectable versus detectable MPTF was compared across strata using Fisher's Exact test. Results MPTF activity was more frequently detected among patients with HCV-monoinfection (40%), compared to HIV-monoinfection and HIV/HCV-seropositive with cleared HCV (7%) and HIV/HCV-coinfection with CHC (14%) (pβ=β0.02). Mean TE-derived liver stiffness score in kPa was higher in patients with detectable MPTF (12.4βΒ±β8.5) than those with undetectable MPTF (6.4βΒ±β3.0) (pβ=β0.01). Mean CD4β+βHLADR+ and CD4β+βCD38-HLADR+ expression were higher in those with detectable MPTF (44βΒ±β9.8% and 38βΒ±β8.7%, respectively) than those with undetectable MPTF (36βΒ±β11% and 31βΒ±β10.4% respectively) (pβ=β0.05 and 0.04 respectively). Conclusions HCV-monoinfection and HIV/HCV-coinfection with CHC were associated with MPTF activity. MPTF activity is also associated with advanced liver fibrosis and with CD4β+βHLADR+ immune activation