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Serum Interferon (serum + interferon)
Selected AbstractsCpG oligodeoxynucleotides accelerate reovirus type 2-triggered insulitis in DBA/1 suckling miceINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2002T. Hayashi Summary. We reported previously that reovirus type-2 (Reo-2) triggers T-helper (Th) 1-mediated autoimmune insulitis resulting in temporal impaired glucose tolerance (IGT) approximately 10 days post infection (d.p.i) in suckling DBA/1 mice. We hypothesized that CpG motifs in bacteria may enhance virus-induced insulitis through its content of unmethylated CpG motifs. In the infected mice, the intraperitoneal treatment of synthetic 20-base oligodeoxynucleotides with CpG motifs (CpG ODN) caused increase in cumulative incidence of insulitis with IGT, increased serum interferon (IFN)-, concentration, and high frequency of autoantibody against pancreatic islet cells, compared to the infected mice without CpG ODN at 17 d.p.i. Also CD4+ and CD8+ lymphocytes infiltrated in and/or around pancreatic islets in the CpG ODN-treated mice. This evidence suggests that CpG ODN may contribute to accelerate Reo-2-induced autoimmune reaction against pancreatic islet cells via additional effects of Th1 cytokines especially IFN-,. [source] Increased circulating and intrahepatic T-cell-specific chemokines in chronic hepatitis C: relationship with the type of virological response to peginterferon plus ribavirin combination therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2004A. Apolinario Summary Aims :,To determine the serum and intrahepatic levels of T-helper-1-associated chemokines in patients with chronic hepatitis C before, during and after peginterferon plus ribavirin combination therapy and to search for correlations with baseline characteristics of hepatitis C virus-related chronic liver disease and type of therapeutic response. Methods :,Serum chemokine levels were determined by enzyme-linked immunosorbent assays and intrahepatic chemokine messenger RNA and protein levels were tested by ribonuclease protection assay and immunohistochemistry. Results :,Serum and intrahepatic chemokine levels were elevated in all patients with chronic hepatitis C and showed a marked decrease in patients who obtained a virological response vs. non-responders. Increased serum interferon-,-inducible protein-10 levels at baseline in genotype 1-infected patients were significantly associated with greater degrees of intrahepatic inflammation and fibrosis (P = 0.0046 and P = 0.02, respectively) and with virological non-response (P = 0.01). In patients with genotype 1, basal serum interferon-,-inducible protein-10 levels greater than 299 pg/mL identified 80% of non-responders and lower than 299 pg/mL identified 63% of responders. Conclusions :,Circulating and intrahepatic T-helper-1-associated chemokines are abnormally elevated in patients with chronic hepatitis C. Increased baseline serum interferon-,-inducible protein-10 levels in genotype 1-infected patients are associated with virological non-response to peginterferon plus ribavirin combination therapy. [source] Genetic variation at the IRF7/PHRF1 locus is associated with autoantibody profile and serum interferon-, activity in lupus patientsARTHRITIS & RHEUMATISM, Issue 2 2010Rafah Salloum Objective Interferon-, (IFN,) is a heritable risk factor for systemic lupus erythematosus (SLE). Genetic variation near IRF7 is implicated in SLE susceptibility. SLE-associated autoantibodies can stimulate IFN, production through the Toll-like receptor/IRF7 pathway. This study was undertaken to determine whether variants of IRF7 act as risk factors for SLE by increasing IFN, production and whether autoantibodies are important to this phenomenon. Methods We studied 492 patients with SLE (236 African American, 162 European American, and 94 Hispanic American subjects). Serum levels of IFN, were measured using a reporter cell assay, and single-nucleotide polymorphisms (SNPs) in the IRF7/PHRF1 locus were genotyped. Results In a joint analysis of European American and Hispanic American subjects, the rs702966 C allele was associated with the presence of anti,double-stranded DNA (anti-dsDNA) antibodies (odds ratio [OR] 1.83, P = 0.0069). The rs702966 CC genotype was only associated with higher serum levels of IFN, in European American and Hispanic American patients with anti-dsDNA antibodies (joint analysis P = 4.1 × 10,5 in anti-dsDNA,positive patients and P = 0.99 in anti-dsDNA,negative patients). In African American subjects, anti-Sm antibodies were associated with the rs4963128 SNP near IRF7 (OR 1.95, P = 0.0017). The rs4963128 CT and TT genotypes were associated with higher serum levels of IFN, only in African American patients with anti-Sm antibodies (P = 0.0012). In African American patients lacking anti-Sm antibodies, an effect of anti-dsDNA,rs702966 C allele interaction on serum levels of IFN, was observed, similar to the other patient groups (overall joint analysis P = 1.0 × 10,6). In European American and Hispanic American patients, the IRF5 SLE risk haplotype showed an additive effect with the rs702966 C allele on IFN, level in anti-dsDNA,positive patients. Conclusion Our findings indicate that IRF7/PHRF1 variants in combination with SLE-associated autoantibodies result in higher serum levels of IFN,, providing a biologic relevance for this locus at the protein level in human SLE in vivo. [source] Elevated serum interferon-, activity in juvenile dermatomyositis: Associations with disease activity at diagnosis and after thirty-six months of therapyARTHRITIS & RHEUMATISM, Issue 6 2009Timothy B. Niewold Objective Interferon-, (IFN,) has been implicated in the pathogenesis of juvenile dermatomyositis (DM). The aim of this study was to examine serum IFN, activity in a cohort of children with juvenile DM to determine relationships between IFN, and indicators of disease activity and severity. Methods Thirty-nine children with definite/probable juvenile DM were included in the study. Serum samples were obtained at the time of diagnosis from 18 untreated patients with juvenile DM. Second samples from 11 of these patients were obtained at 24 months, while they were receiving treatment, and third samples were obtained from 7 of these patients at 36 months. The remaining 21 children were studied 36 months after their initial diagnosis. Serum IFN, activity was measured using a functional reporter cell assay. Results Patients with juvenile DM had higher serum IFN, activity than both pediatric and adult healthy control subjects. In untreated patients, serum IFN, activity was positively correlated with serum muscle enzyme levels (P < 0.05 for creatine kinase, aspartate aminotransferase, and aldolase) and inversely correlated with the duration of untreated disease (P = 0.017). The tumor necrosis factor , ,308A allele was associated with higher serum IFN, levels only in untreated patients (P = 0.030). At 36 months, serum IFN, levels were inversely correlated with muscle enzyme levels in those patients still requiring therapy and with the skin Disease Activity Score in those patients who had completed therapy (P = 0.002). Conclusion Serum IFN, activity was associated with higher serum levels of muscle-derived enzymes and a shorter duration of untreated disease in patients with newly diagnosed juvenile DM and was inversely correlated with measures of chronic disease activity at 36 months postdiagnosis. These data suggest that IFN, could play a role in disease initiation in juvenile DM. [source] The PTPN22 C1858T polymorphism is associated with skewing of cytokine profiles toward high interferon-, activity and low tumor necrosis factor , levels in patients with lupusARTHRITIS & RHEUMATISM, Issue 9 2008Silvia N. Kariuki Objective The C1858T polymorphism in PTPN22 has been associated with the risk of systemic lupus erythematosus (SLE) as well as multiple other autoimmune diseases. We have previously shown that high serum interferon-, (IFN,) activity is a heritable risk factor for SLE. The aim of this study was to determine whether the PTPN22 risk variant may shift serum cytokine profiles to higher IFN, activity, resulting in risk of disease. Methods IFN, was measured in 143 patients with SLE, using a functional reporter cell assay, and tumor necrosis factor , (TNF,) was measured by enzyme-linked immunosorbent assay. The rs2476601 single-nucleotide polymorphism in PTPN22 (C1858T) was genotyped in the same patients. Patients were grouped, using a clustering algorithm, into 4 cytokine groups (IFN, predominant, IFN, and TNF, correlated, TNF, predominant, and both IFN, and TNF, low). Results SLE patients carrying the risk allele of PTPN22 had higher serum IFN, activity than patients lacking the risk allele (P = 0.027). TNF, levels were lower in carriers of the risk allele (P = 0.030), and the risk allele was more common in patients in the IFN,-predominant and IFN, and TNF,-correlated groups as compared with patients in the TNF,-predominant and both IFN, and TNF,-low groups (P = 0.001). Twenty-five percent of male patients carried the risk allele, compared with 10% of female patients (P = 0.024); however, cytokine skewing was similar in both sexes. Conclusion The autoimmune disease risk allele of PTPN22 is associated with skewing of serum cytokine profiles toward higher IFN, activity and lower TNF, levels in vivo in patients with SLE. This serum cytokine pattern may be relevant in other autoimmune diseases associated with the PTPN22 risk allele. [source] Age- and sex-related patterns of serum interferon-, activity in lupus familiesARTHRITIS & RHEUMATISM, Issue 7 2008Timothy B. Niewold Objective Interferon-, (IFN,) levels are elevated in many patients with systemic lupus erythematosus (SLE) and may play a primary role in its pathogenesis. The purpose of this study was to determine whether serum IFN, activity in SLE patients and their healthy first-degree relatives is highest in early adulthood, when the incidence of SLE is greatest. Methods Serum samples from 315 SLE patients, 359 healthy first-degree relatives, and 141 healthy unrelated donors were measured for IFN, activity using a functional reporter cell assay. IFN, activity was analyzed in relation to age, and subgroups with high levels of IFN, activity were identified within the large data sets using a Mann-Whitney sliding window segmentation algorithm. The significance of each subgrouping was ranked by Kruskal-Wallis testing. Results Age was inversely correlated with IFN, activity in female SLE patients (r = ,0.20, P = 0.001) as well as their healthy female first-degree relatives (r = ,0.16, P = 0.02). In male patients and their healthy male first-degree relatives, there was no significant overall correlation between age and serum IFN, activity. The segmentation algorithm revealed significantly increased IFN, activity between the ages of 12 and 22 years in female SLE patients and between the ages of 16 and 29 years in male SLE patients. Both male and female healthy first-degree relatives had significantly decreased IFN, activity after the age of 50 years. Conclusion Serum IFN, activity is higher in younger individuals in the SLE family cohorts, and this tendency is accentuated in affected individuals. This age-related pattern of IFN, activity may contribute to the increased incidence of SLE in early adulthood, and interestingly, males and females had similar age-related patterns of IFN, activity. [source] Chemical induction of HO-1 suppresses lupus nephritis by reducing local iNOS expression and synthesis of anti-dsDNA antibodyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2004Y. TAKEDA SUMMARY There is accumulating evidence that haem oxygenase (HO)-1 plays a protective role in various disorders. The beneficial efficacy of HO-1 induction therapy has been shown in renal diseases such as glomerulonephritis, interstitial nephritis and drug induced nephrotoxicity. However, involvement of HO-1 in the development of autoimmune renal diseases remains uncertain. To assess the clinical efficacy of HO-1 induction therapy for lupus glomerulonephritis, MRL/lpr mice were intraperitoneally injected with 100 µmol/kg hemin, a potent HO-1 inducer, or PBS as controls, once a week from 6 weeks of age to 21,24 weeks-old. We found that treatment with hemin led to a significant reduction of proteinuria and remarkable amelioration of glomerular lesions accompanied by decreased immune depositions. In addition, the circulating IgG anti-double-stranded DNA antibody level was significantly decreased in hemin treated mice when compared with controls. A single intraperitoneal injection with hemin resulted in reduction of inducible nitric oxide synthase expression in the kidney and spleen, and serum interferon- , level. Our results suggest that HO-1 induction therapy ameliorates lupus nephritis by suppressing nitric oxide (NO) dependent inflammatory responses and attenuating production of pathogenic autoantibodies. [source] | ||||||||||