Serum Interferon-γ-inducible Protein-10 Research Articles

Performance analysis of Luminex and ELISA to profile serum IP-10 as a biomarker in systemic lupus erythematosus.

Interferon-γ inducible protein-10 (IP-10) is a promising biomarker in systemic lupus erythematosus (SLE). The optimal quantification platform has not yet been identified. We compared the performance of bead-based multiplex assay (Luminex) and high-sensitivity enzyme-linked immunosorbent assay (hs-ELISA) for profiling serum IP-10 as a biomarker of lupus activity. A cross-sectional study was conducted on outpatients with SLE. Serum IP-10 was measured simultaneously on Luminex and hs-ELISA, and correlation between platforms was assessed. Additionally, IP-10 levels were tested against disease activity and organ involvement. One-hundred and forty-one patients (88% women; 38 years old) were studied. Median IP-10 levels were 100.9 (125.2) pg/mL by Luminex and 156.5 (191.7) pg/mL by hs-ELISA. Correlation analysis showed Spearman's ρ = 0.621 (p < 0.0001) between Luminex and hs-ELISA. Quantification of IP-10 by Luminex showed a significant correlation (ρ = 0.198; p = 0.021) with disease activity, while this was not observed (ρ = 0.036; p = 0.683) when measured using hs-ELISA. Serum IP-10 levels were lower in quiescent patients than in those with active disease (70.8 [68.4] versus 114.3 [123.9] pg/mL; p = 0.024), with an AUC-ROC = 0.62 (p = 0.029), sensitivity = 47.9%, specificity = 77.5%, and positive likelihood ratio = 2.1. Patients with active arthritis had higher IP-10 levels than non-arthritis patients (158.1 [505.4] versus 94.1 [114.0] pg/mL; p = 0.008), with an AUC-ROC = 0.73 (p = 0.0009), sensitivity = 72.7%, specificity = 66.4%, and positive likelihood ratio = 2.1. No other type of organ involvement was identified by serum IP-10. Luminex performs better than hs-ELISA as a quantification platform for IP-10 as it correlates with disease activity and identifies active arthritis in SLE.

Changes in serum interferon-γ-inducible protein-10 levels and liver stiffness among chronic hepatitis C Egyptian patients in response to directly acting antiviral agents.

Interferon-γ inducible protein-10 (IP-10) is chemokine biomarker of liver inflammation, elevated in patients with chronic hepatitis C infection. Investigating if changes in serum IP-10 levels in response to directly acting antiviral agents (DAAs) treatment for chronic HCV patients are paralleled by changes in liver stiffness measurements (LSM), and assessing role of using serum IP-10 as a noninvasive accurate method to predict changes in hepatic necro-inflammation and fibrosis. A prospective observational study included 92 Egyptian chronic HCV patients, who received treatment with sofosbuvir with daclatasvir regimen. Patients were classified into two groups; group I (53 patients) with non to mild significant liver fibrosis (F0-F1), and group II (39 patients) with significant to advanced liver fibrosis (F2-F4). Fibroscan and serum IP-10 were assessed pretreatment and 3 months after end of treatment. All patients achieved SVR. Both IP-10 and LSM showed significant decline after treatment in both groups. No significant correlation was found between changes in LSM and IP-10. IP-10 detected liver cirrhosis at cut off level of 17.8 pg/ml, with 75% sensitivity and 73.86% specificity, with area under the curve = 0.66, however, IP-10 had no statistical significance in detecting advanced fibrosis. IP-10 might be of significance as a noninvasive predictor of liver cirrhosis. IP-10 significant decline post-DAAs treatment in chronic HCV genotype IV infected patients reflects significant improvement in fibrosis stage and hepatic necro-inflammation in response to treatment. No significant correlation was detected in the changes of both IP-10 and LSM.

Interferon-γ inducible protein-10 and interleukin 28B gene polymorphism as predictive markers for genotype 4 hepatitis C virus treatment response.

HCV genotype 4 dominates the HCV epidemic in Egypt. Drug resistance was the most serious side effect that reflects bad clinical outcome. Several studies had demonstrated that baseline serum interferon-γ-inducible-protein 10 (IP-10) levels and interleukin 28B polymorphisms were associated with the resistance to the standard of care pegylated interferon alpha and ribavirin (PEG-IFNα/RBV) therapy and development of post-treatment relapse. Our purpose was to assess the predictive value of combining IP-10 levels and IL28B genotypes to PEG-IFNα/RBV therapy response in Egyptian chronic HCV infection patients with genotype 4. Ninety Egyptian patients chronically infected by HCV genotype-4 treated with pegylated interferon alpha and ribavirin (PEG-IFNα/RBV) therapy were enrolled. Serum IP-10 levels were determined by enzyme linked immunosorbent assay pre- and post- treatment. IL-28B (rs12979860 and rs8099917) polymorphisms were performed by PCR-RFLP in all patients. Overall, 38 patients (42.2%) achieved sustained virologic response (SVR) and 52 (57.8%) patients have non-viral response (NVR). Pretreatment serum IP-10 mean levels were significantly lower in patients who achieved SVR than in NVR (P<0.05). CC genotype in IL28B polymorphism (rs12979860) was the favorable genotype as 65.8% achieved SVR, while TT genotype in IL-28B polymorphism (rs8099917) was the favorable genotype as 81.5% achieved SVR. Baseline IP-10 was significantly correlated to genotypes CC in rs12979860 and TT in rs8099917. Combined use of serum baseline IP-10 levels with IL-28B polymorphisms could improve the prediction of SVR to PEG-IFNα/RBV therapy in Egyptian chronic HCV infection patients with genotype 4.

Interferon-gamma inducible protein IP-10 and left ventricular remodelling post-acute myocardial infarction: a longitudinal cardiovascular magnetic resonance imaging substudy of CAPRI clinical trial

Abstract Background Adverse left ventricular (LV) remodelling is associated with development of heart failure and poor outcomes in patients with acute myocardial infarction (AMI). Understanding the immunomodulatory mechanisms of LV remodelling is an essential step for the development of novel therapies. Interferon-γ-inducible protein-10 (IP-10)/CXCL10 is a chemokine involved in the recruitment of activated T cells into sites of tissue inflammation. Although IP-10 was reported to reduce adverse LV remodeling in a preclinical myocardial infarction model, its role in LV remodeling in humans with AMI remains unknown. Purpose To determine the clinical predictive value of serum IP-10 in LV remodeling in patients with ST-segment elevation myocardial infarction (STEMI). Methods This is a substudy of the double-blind, randomised controlled trial “Evaluating the effectiveness of intravenous ciclosporin on reducing reperfusion injury in patients undergoing primary percutaneous coronary intervention” (CAPRI; ClinicalTrials.gov registry number NCT02390674), which enrolled 52 acute STEMI patients. LV remodeling was assessed by cardiovascular magnetic resonance (CMR) imaging and was defined as the 12-week vs. the 3-day post-myocardial infarction change of the left ventricular ejection fraction (ΔLVEF), LV end-diastolic volume (ΔEDV) or LV end-systolic volume (ΔESV). Serum IP-10 was measured before and 5min, 15min, 30min, 90min and 24h after reperfusion by ELISA. Linear regression analysis was used to determine the independent association of IP-10 with the endpoints of the study. Results Serum IP-10 concentration peaked at 30min after reperfusion followed by a 2-fold decrease at the 24h post reperfusion compared to pre-reperfusion levels (P&amp;lt;0.001 for all). Comparison of the 12-week CMR to the baseline CMR imaging revealed that baseline pre-reperfusion as well as 5min, 15min, 30min and 90min, but not 24h, post-reperfusion IP-10 serum levels associated with increased LVEF and decreased ESV at 12-weeks (range correlation coefficient r=[0.35–0.41], P&amp;lt;0.05 with ΔLVEF and r=[−0.33 to −0.44], P&amp;lt;0.05 with ΔESV) indicating that the increase of IP-10 at the acute phase of myocardial infarction confers a cardioprotective role. Multivariable linear regression analysis for ΔLVEF showed that in a model including baseline pre-reperfusion or 5min or 15min or 30min or 90min post-reperfusion IP-10 and age, gender, traditional risk factors (arterial hypertension, body-mass index, hyperlipoproteinemia, diabetes mellitus, smoking, family history of CAD), infarct location, admission high-sensitivity troponin T, door-to-balloon time and ciclosporin treatment, only IP-10 was the independent determinant of ΔLVEF. Conclusions Increased serum IP-10 levels early after reperfusion are associated with reverse LV remodeling in patients with STEMI undergoing primary PCI. The clinical application of IP-10 as a novel biomarker of LV remodeling post-AMI should be further explored and validated. Funding Acknowledgement Type of funding source: None

Serum cytokine profiles and Mac-2 binding protein glycosylation isomer (M2BPGi) level in patients with autoimmune hepatitis.

Autoimmune hepatitis (AIH) is an autoimmune liver disease that is characterized by a progressive destruction of the liver parenchyma and the development of liver fibrosis. We aimed to examine the relationship between circulating cytokines/chemokines and the Mac-2 binding protein glycosylation isomer (M2BPGi) levels in Japanese patients with autoimmune hepatitis (AIH).We investigated the relationship between circulating cytokines/chemokines and M2BPGi levels in Japanese patients with AIH. Seventy-seven patients with well-documented AIH were enrolled in the National Hospital Organization (NHO)-AIH-liver-network database. We measured the serum levels of 20 cytokines in 31 selected AIH patients before and after steroid treatment using multisuspension cytokine array.Eleven cytokines and soluble adhesion molecules were increased in untreated AIH patients compared with treated AIH patients. Among these cytokines and soluble adhesion molecules, soluble intercellular adhesion molecule-1 (sICAM-1) and interferon-γ-inducible protein 10 (IP-10) were most downregulated by steroid therapy in AIH patients. We measured serum sICAM-1 and IP-10 by ELISA and found the levels were significantly higher in AIH patients (n = 77) compared with chronic viral hepatitis C patients (n = 32). Furthermore, there was a positive correlation between sICAM-1 or IP-10 and alanine aminotransferase, total bilirubin, and circulating M2BPGi levels. M2BPGi levels were increased in AIH patients with high stages of liver fibrosis. Additionally, M2BPGi levels were correlated with the histological grade of inflammation in AIH. Circulating M2BPGi levels were significantly reduced by steroid treatment in AIH patients.sICAM-1 and IP-10 are useful markers to assess immune-mediated hepatitis activity in AIH and they correlate with circulating M2BPGi. Serum M2BPGi levels increased in untreated AIH patients with active hepatitis and were decreased by steroid therapy. M2BPGi reflects autoimmune-mediated hepatic inflammation as well as liver fibrosis.

Elevated serum interferon γ-inducible protein-10 in women with polycystic ovary syndrome

Background: Interferon γ-induced protein 10 kDa (IP10/CXCL10) is a chemokine related to endocrine disorders; however, the serum concentrations of IP10 in women with polycystic ovary syndrome (PCOS) have not yet been reported. Therefore, we investigated whether IP10 is increased in PCOS patients and its potential clinical value in PCOS patients.Methods: For this research, the serum IP10, glucose, insulin, high sensitivity C-reactive protein (hs-CRP), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and total testosterone (TT) concentrations were measured in 60 women with PCOS and healthy controls.Results: The median IP10 concentration was 45.60 pg/mL [interquartile range (IQR):29.75, 79.69], which was significantly higher than that of the body mass index (BMI)-matched controls (median: 36.46 pg/mL; IQR:28.98, 45.80). In the multivariate linear regression analysis, hs-CRP and the homeostasis model assessment of insulin resistance index (HOMA2-IR) were independent predictors of the IP10 values, while FSH was inversely associated with the IP10.No significant association was observed between the IP10 and BMI, glucose, LH and TT.Conclusions: The serum IP10 concentrations increase in women with PCOS, moreover, IP10 appears to be correlated with the inflammatory and IR statuses of PCOS. IP10 may be a potential biomarker to estimate the disease activity of PCOS.

Study of interferon-γ-inducible protein-10 levels during antiviral therapy of hepatitis C patients with sofosbuvir plus ribavirin and interferon in Menoufia hospitals

Objective The aim of this work was to study the effect of treatment with sofosbuvir, ribavirin, and interferon on the level of interferon-γ-inducible protein-10 (IP-10) and to determine its role in hepatitis C virus (HCV) patients with liver cirrhosis. Background IP-10 is a small cytokine belonging to the CXC chemokine secreted by several cell types in response to interferons (interferon-γ). IP-10 has been attributed to several roles, such as chemoattraction for monocytes, macrophages, T cells, natural killer cells, and dendritic cells, promotion of T cell adhesion to endothelial cells, antitumor activity, and inhibition of bone marrow colony formation and angiogenesis. Patients and methods The study was conducted on 27 hepatitis C patients with cirrhosis and 15 age-matched and sex-matched healthy individuals. Serum levels of IP-10 were measured in patients using enzyme-linked immunosorbent assay technique three times: before beginning the treatment, after 1 week of treatment, and finally after 3 months of treatment. IP-10 levels were statistically analyzed in relation to liver cirrhosis and treatment outcome. Results IP-10 serum levels were highly elevated in patients when compared with healthy people. Serum IP-10 was significantly higher before beginning HCV treatment and then decreased after 1 week of treatment, and it was markedly decreased after 3 months of treatment. Conclusion IP-10 had a fundamental role in the pathogenesis of liver fibrosis and cirrhosis as it was significantly elevated in cirrhotic patients. Furthermore, there was a significant reduction in serum IP-10 concentration following a successful course of HCV treatment.

B-Cell Activating Factor Belonging to the Tumor Necrosis Factor Family and Interferon-γ-Inducible Protein-10 in Autoimmune Hepatitis.

The aims of the present study were to examine the relationship between serum B-cell activating factor belonging to the tumor necrosis factor family (BAFF) levels and serum interferon-γ-inducible protein-10 (IP-10) levels in patients with autoimmune hepatitis (AIH).A total of 80 corticosteroid therapy naive AIH patients were analyzed in this analysis. First, we examined the relationship between pretreatment serum BAFF and IP-10 levels and liver histological findings. Next, we investigated the relationship of pretreatment serum BAFF and IP-10 levels and aspartate aminotransferase value (AST), alanine aminotransferase value, and serum Immunoglobulin G (IgG) level as serum liver inflammation markers.Our study included 14 men and 66 women with the median (range) age of 64 (21–83) years. The serum BAFF levels ranged from 122.5 to 7696.0 pg/mL (median value, 1417.8 pg/mL), whereas the serum IP-10 levels ranged from 142.0 to 4198.7 pg/mL (median value, 640.1 pg/mL). The serum BAFF levels were significantly stratified in each 2 liver inflammation stage. Similarly, the serum IP-10 levels were significantly stratified in each 2 liver inflammation stage. Among 3 serum inflammation markers, AST value had the highest rs value in terms of the relationship with BAFF level (rs = 0.511, P < 0.001) and IP-10 level (rs = 0.626, P < 0.001). In addition, the serum BAFF level significantly correlated with serum IP-10 level (rs = 0.561, P < 0.001). In patients without advanced fibrosis (F3 or more), the serum BAFF level significantly correlated with serum IP-10 level (rs = 0.658, P < 0.001), whereas in patients with advanced fibrosis, the serum BAFF level significantly correlated with serum IP-10 level (rs = 0.542, P < 0.001).In conclusion, both BAFF and IP-10 are useful for predicting the degree of liver inflammation activity in AIH. BAFF and IP-10 may have the common clinical implication for liver inflammation activity for AIH patients.

Impact of serum Wisteria floribunda agglutinin positive Mac-2-binding protein and serum interferon-γ-inducible protein-10 in primary biliary cirrhosis.

We aimed to examine the relationship between serum Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA(+) -M2BP) levels and serum interferon-γ-inducible protein-10 (IP-10) levels and liver histological findings for patients with primary biliary cirrhosis (PBC) compared with other laboratory fibrotic or inflammatory parameters. A total of 57 PBC patients were analyzed. Receiver-operator curve (ROC) analysis was performed for calculating the area under the ROC (AUROC) for WFA(+) -M2BP, IP-10 and four serum fibrosis markers for the presence of liver cirrhosis (F4) or advanced fibrosis (F3 or F4). Similarly, ROC analysis of WFA(+) -M2BP, IP-10, aspartate aminotransferase and alanine aminotransferase for the presence of severe inflammation activity (A3) was performed. There were eight men and 49 women (median age, 59years). As for histological findings, F4 was observed in five patients, F3 in 11, F2 in 17, F1 in 24 and F0 in zero, whereas A3 was observed in seven patients, A2 in 27, A1 in 19 and A0 in four. The WFA(+) -M2BP levels ranged from 0.5 cut-off index (COI) to 13.6 COI (median, 1.8), while serum IP-10 levels ranged 121.9-1835.9pg/mL (median, 571.5). For predicting liver cirrhosis, WFA(+) -M2BP yielded the highest AUROC (0.97, P <0.01). For predicting severe liver inflammation activity (A3), WFA(+) -M2BP and serum IP-10 yielded the highest AUROC with a level of 0.87. WFA(+) -M2BP levels significantly correlated with serum IP-10 levels (rs = 0.55, P <0.0001). Serum WFA(+) -M2BP and serum IP-10 can be useful markers for predicting histological findings in PBC patients.

Association of IL28B Genotypes and Baseline Serum Interferon-γ-Inducible- Protein-10 Levels with Treatment Response in Hepatitis C Virus Patients in China.

Background/AimsSeveral studies have demonstrated that serum interferon-γ-inducible-protein-10 (IP-10) levels at baseline and single nucleotide polymorphisms (SNPs) near the IL28B gene were associated with viral response and treatment outcomes. Our purpose was to assess the combination of pretreatment IP-10 levels with IL28B SNPs as predictors of treatment response to pegylated interferon α-2a plus ribavirin in patients infected with genotype 1 hepatitis C virus in China.MethodsSeventy-two patients with chronic hepatitis C without fibrosis/cirrhosis were enrolled in the study. The virologic parameters and baseline serum IP-10 levels were determined. IL-28B genotypes were determined by sequencing.ResultsIn this cohort, serum baseline IP-10 levels lower than 426.7 pg/mL could predict rapid virological response/sustained virological response (SVR). Patients carrying favorable IL28B SNP genotypes had higher SVRs than did those carrying unfavorable variants (IL28B rs12979860, p=0.002; IL28B rs8099917, p=0.020). Combining both baseline IP-10 and IL28B SNPs could improve the prediction of SVR in favorable allele carriers of IL28B, rs12979860 CC and rs8099917 TT. Serum baseline IP-10 levels and IL28B genotypes were independent predictors of SVR.ConclusionsOur study shows that the combination of baseline serum IP-10 levels and the determination of IL28B SNPs increase the predictability of SVR rates in this cohort.

IP-10 Serum Level in Chronic Hepatitis C Virus Patients: Relation to Fibrosis and Response to Combined Interferon/Ribavirin Therapy.

Despite the appearance of the direct acting antiviral drugs, pegylated interferon/ribavirin (PEG-IFN/RBV) still has a place in the standard of care (SOC) therapy for chronic HCV4. Studies were conducted to find an accurate prediction in response to SOC therapy. Pretreatment serum interferon-γ-inducible protein-10 (IP-10) is an independent predictive factor of sustained virological response (SVR) in HCV1-infected patients. To assess whether the pretreatment serum level of IP-10 influences hepatic fibrosis and PEG-IFN/RBV therapy response, a study was conducted on 88 chronic Hepatitis C virus (HCV) patients who received PEG-IFN/RBV. Patients were subjected to a pretreatment routine laboratory evaluation, liver biopsy, and serum IP-10 assessment. They were followed up for 6 months after cessation of therapy (week 72). Patients were classified into 3 groups according to their response; nonresponders, relapsers, or sustained virological responders. The relation of pretreatment IP-10 with fibrosis and response was assessed. The studied groups were matched regarding their demographic data. There was no statistically significant association between the pretreatment IP-10 level and fibrosis (P=0.86) and no relation to response was found at week 12, 24, 48, and 72 (P=0.58, 0.8, 0.47, and 0.43, respectively). Pretreatment IP-10 could not predict either fibrosis or response to PEG-IFN/RIB therapy in chronic HCV Egyptian patients.

Serum interferon-gamma-inducible protein-10 concentrations andIL28Bgenotype associated with responses to pegylated interferon plus ribavirin with and without telaprevir for chronic hepatitis C

Several studies have shown that high pretreatment concentrations of serum interferon-γ-inducible protein-10 (IP-10) are correlated with non-response to pegylated interferon (PEG-IFN) plus ribavirin (RBV) for chronic hepatitis C (CHC). However, there are few reports on their effect on the Asian population. We enrolled 104 Japanese genotype 1 CHC individuals treated with PEG-IFN/RBV and 45 with PEG-IFN/RBV/telaprevir, and evaluated the impact of pretreatment serum IP-10 concentrations on their virological responses. The pretreatment serum IP-10 concentrations were not correlated with IL28B genotype. The receiver-operator curve analysis determined the cut-off value of IP-10 for predicting a sustained virological response (SVR) as 300 pg/mL. In multivariate analysis, the IL28B favorable genotype and IP-10 concentration of less than 300 pg/mL were independent factors for predicting SVR. In a subgroup of patients with the IL28B favorable genotype, the SVR rate was higher in the patients with IP-10 of less than 300 than in those with 300 pg/mL or more, whereas no patient with the IL28B unfavorable genotype and IP-10 of 300 pg/mL or more achieved SVR. Among the patients treated with PEG-IFN/RBV/telaprevir, low pretreatment concentrations of serum IP-10 were associated with a very rapid virological response, defined as undetectable HCV RNA at week 2 after the start of therapy. Pretreatment serum IP-10 concentrations are associated with treatment efficacy in PEG-IFN/RBV and with early viral kinetics of hepatitis C virus in PEG-IFN/RBV/telaprevir therapy.

Serum and urinary MIP-1α and IP-10 levels in children with urinary tract infections.

Urinary tract infection (UTI) is a common bacterial disease in infants and children, with potentially serious complications, including kidney damage. The aim of this study was to test whether serum and urinary levels of interleukin-6 (IL-6), macrophage inflammatory protein-1a (MIP-1a) and interferon-γ-inducible protein-10 (IP-10) can be used as biomarkers in children with urinary tract infections. The study group consisted of 22 children with UTI and 20 controls. Blood and urine samples were collected in the acute phase and the convalescent phase, on the eighth day after the onset of antibiotic therapy. Serum and urine levels of MIP-1a, IP-10 and IL-6 were measured. In children with UTI in the acute phase, serum MIP-1a and IL-6 levels were significantly higher compared to the controls (p<0.05 and p<0.005, respectively). A correlation between the serum levels of the chemokines MIP-1a and IP-10 in the acute phase was found. The findings suggest that the chemokines MIP-1a or IP-10 respond to infection, but they cannot be used as biomarkers for UTI in childhood.

Serum IP-10 Levels Correlate with the Severity of Liver Histopathology in Patients Infected with Genotype-1 HCV

Background/AimsInterferon-γ-inducible protein 10 (IP-10) plays important roles in the pathogenesis of hepatitis C virus (HCV) infection. We investigated the association between serum IP-10 levels and liver pathology in patients with chronic HCV infection.MethodsThe serum IP-10 concentration was assessed in 85 patients with chronic HCV infection using a solid phase sandwich enzyme-linked immunosorbent assay, and a liver biopsy specimen was obtained. The pathology was scored using the Knodell histologic activity index (HAI).ResultsOf the 85 patients, 58 had genotype 1 HCV infection, 21 had genotype non-1, and 6 were undetermined. The serum IP-10 levels did not differ between patients infected with genotype 1 and genotype non-1 (p=0.472). In patients with genotype 1 infection, the total HAI score and the stage of fibrosis were highly correlated with the serum IP-10 level (r=0.555, r=0.578, p<0.001). Furthermore, the serum IP-10 concentrations of patients with severe fibrosis (stages 3, 4) were higher than those of patients with mild fibrosis (stages 0 to 2; 214.4 vs. 72.3 pg/mL, p=0.002) among patients with genotype 1 infection. However, in patients without genotype 1 infection, the histopathology was not associated with the serum IP-10 level. A multivariate analysis showed that serum IP-10 was an independent predictor of fibrosis (stages 3, 4) in patients with genotype 1 infection (odds ratio, 1.034; 95% confidence interval, 1.006 to 1.064; p=0.018).ConclusionsSerum IP-10 concentration was significantly correlated with the severity of liver histology in genotype 1 HCV infection.

Quantitation of pretreatment serum interferon-γ-inducible protein-10 improves the predictive value of an IL28B gene polymorphism for hepatitis C treatment response

Polymorphisms of the IL28B gene are highly associated with sustained virological response (SVR) in patients with chronic hepatitis C treated with peginterferon and ribavirin. Quantitation of interferon-γ-inducible protein-10 (IP-10) may also differentiate antiviral response. We evaluated IP-10 levels in pretreatment serum from 115 nonresponders and 157 sustained responders in the Study of Viral Resistance to Antiviral Therapy of Chronic Hepatitis C cohort, including African American (AA) and Caucasian American (CA) patients. Mean IP-10 was lower in sustained responders compared with nonresponders (437 ± 31 vs 704 ± 44 pg/mL, P < 0.001), both in AA and CA patients. The positive predictive value of low IP-10 levels (<600 pg/mL) for SVR was 69%, whereas the negative predictive value of high IP-10 levels (>600 pg/mL) was 67%. We assessed the combination of pretreatment IP-10 levels with IL28B genotype as predictors of treatment response. The IL28B polymorphism rs12979860 was tested in 210 participants. The CC, CT, and TT genotypes were found in 30%, 49%, and 21% of patients, respectively, with corresponding SVR rates of 87%, 50%, and 39% (P < 0.0001). Serum IP-10 levels within the IL28B genotype groups provided additional information regarding the likelihood of SVR (P < 0.0001). CT carriers with low IP-10 had 64% SVR versus 24% with high IP-10. Similarly, a higher SVR rate was identified for TT and CC carriers with low versus high IP-10 (TT, 48% versus 20%; CC, 89% versus 79%). IL28B genotype and baseline IP-10 levels were additive but independent when predicting SVR in both AA and CA patients. When IL28B genotype is combined with pretreatment serum IP-10 measurement, the predictive value for discrimination between SVR and nonresponse is significantly improved, especially in non-CC genotypes. This relationship warrants further investigation to elucidate the mechanisms of antiviral response and prospective validation.

Serum IP-10 as a Biomarker of Human Rhinovirus Infection at Exacerbation of COPD

Human rhinovirus (HRV) is the most frequent virus associated with COPD exacerbations. Viral infections increase exacerbation severity and likelihood of hospitalization. As ease of sampling blood makes serum a more practical marker than sputum, we investigated whether changes in serum interferon-gamma-inducible protein 10 (IP-10) from baseline to exacerbation were higher in airway HRV-positive exacerbations and whether IP-10 levels related to HRV load. One hundred thirty-six patients with COPD and 70 controls were included over 2 years and 72 exacerbations sampled. HRV positivity and load were determined by reverse transcriptase-polymerase chain reaction in nasopharyngeal swabs and/or sputum at baseline and exacerbation. IP-10 was measured by enzyme-linked immunosorbent assay in serum and compared with HRV load. At baseline, serum IP-10 was higher in patients with COPD than controls; medians were 149.4 pg/mL (103-215) and 111.7 pg/mL (82-178), P = .02. The presence of HRV at baseline did not increase IP-10: patients with COPD, 166.9 pg/mL (110-240) and 149.4 pg/mL (103-215), P = .30; controls, 136.4 pg/mL (77-204) and 111.7 pg/mL (82-178), P = .53. IP-10 increased significantly from baseline to exacerbation in HRV-positive exacerbations: 154.9 pg/mL (114.0-195.1) to 207.5 pg/mL (142.1-333.5), P = .009. There was no change in IP-10 between baseline and exacerbation in HRV-negative exacerbations: 168.3 pg/mL (94.3-249.8) and 175.6 pg/mL (107.2-290.4), P = .49. At exacerbation, IP-10 correlated with sputum viral load: rho = 0.48; P = .02. In receiver operating characteristics analysis, the combination of IP-10 and coryzal symptoms gave an area under the curve of 0.82 (95% CI, 0.74-0.90). IP-10 increases from baseline to exacerbation in HRV-positive exacerbations and correlates with sputum HRV load. Serum IP-10 may be useful as a novel marker for these events.