Circulating CXCL11 and CXCL10 are increased in hepatitis C-associated cryoglobulinemia in the presence of autoimmune thyroiditis.
ABSTRACT No data are available about circulating levels of the CXCL11 chemokine in hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) patients with or without autoimmune thyroiditis (AT). The aim of the present study, therefore, was to evaluate serum CXCL11 levels in these patients.
Serum CXCL11 (and for comparison, CXCL10) was measured in 45 patients with MC, 45 patients with MC and AT (MC + AT), 45 sex- and age-matched controls without AT (control 1), 45 sex- and age-matched patients with AT without cryoglobulinemia (control 2), and in 45 sex- and age-matched patients with hepatitis C chronic infection without MC (HCV+).
Serum CXCL11 and CXCL10 levels were significantly higher in control 2 than in control 1 (p < 0.01). MC patients had CXCL11 and CXCL10 significantly higher than control 1 (p < 0.01). MC + AT patients had CXCL11 and CXCL10 higher than control 2 (p < 0.01) and MC patients (p = 0.02). Serum CXCL11 levels were not associated with any of the clinical features of cryoglobulinemia in patients with MC and MC + AT, which was the same for CXCL10. CXCL10 and CXCL11 in HCV+ patients were significantly higher than in controls 1 and 2, but lower than in MC or MC+AT patients.
Our study first demonstrates higher serum levels of CXCL11 chemokine in patients with MC than in HCV+ patients, and in particular in the presence of AT.
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ABSTRACT: Chronic infection with hepatitis C virus (HCV) can result in both hepatic and extrahepatic disease and endocrine dysfunction represents an important class of HCV-related extrahepatic disease. The most frequently occurring--and clinically important--of these endocrine disorders are thyroid disease and type 2 diabetes mellitus. In this Review, we evaluate the evidence in support of a link between HCV infection and endocrine-system dysfunction, and discuss potential pathophysiological mechanisms. A meta-analysis of the literature has revealed significant associations between chronic HCV infection, thyroid autoimmunity and hypothyroidism. Furthermore, a high prevalence of thyroid cancer has been reported in HCV-positive patients. Several clinicoepidemiological studies have demonstrated that chronic HCV infection could lead to the development of type 2 diabetes mellitus, possibly as a result of HCV-induced metabolic disturbances. Some researchers have postulated that a type 1 T-helper -cell mediated immune response underpins the association of chronic HCV infection with endocrine disease. Indeed, the available data suggest that a common immunological, type 1 T-helper cell pattern of cytokine expression and activation (via interferon-gamma) could provide the pathophysiological basis for this association. Nonetheless, additional studies will be necessary to elucidate fully all the mechanisms involved in HCV-related endocrine dysfunction.Nature Clinical Practice Endocrinology & Metabolism 02/2009; 5(1):26-34. · 7.55 Impact Factor
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ABSTRACT: Chemokines represent a group of small, secreted proteins mainly involved in navigating leukocytes towards site of inflammation. Some chemokines have been implicated in the pathogenesis of autoimmune diseases, which are characterized by an ectopic retention of leukocytes within the target organ, ultimately leading to loss of function. To determine the chemokines profile expressed in the thyroid gland upon chronic exposure to interferon-gamma (IFNgamma), we analyzed C57BL6 transgenic mice that aberrantly express IFNgamma under control of the thyroglobulin promoter. We compared by reverse transcriptase PCR the thyroidal expression of 10 chemokines (CCL1 through 5 and CXCL9 through 13) in thyr-IFNgamma transgenics and wild-type littermates. We found that transgenics exclusively expressed CCL4, CXCL9, and CXCL11, and showed increased expression of CCL5 and CXCL10. This chemokine profile was associated with moderate mononuclear cell infiltration of the thyroid stroma that, however, decreased significantly after 2 months of age and did not organize into lymphoid structures. Our findings indicate that the isolated expression of IFNgamma is capable of recruiting mononuclear cells but they do not progress to full lymphoid transformation of the thyroid.Experimental and Molecular Pathology 01/2005; 77(3):161-7. · 2.13 Impact Factor
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ABSTRACT: The molecular mechanisms of acute hepatitis C virus (HCV) infection, end-stage hepatitis (cirrhosis), and hepatocellular carcinoma have been extensively studied, but little is known of the changes in liver gene expression during the early stages of liver fibrosis associated with chronic HCV infection, that is, the transition from normal liver (NL) of uninfected patients to the first stage of liver fibrosis (F1-CH-C). To obtain insight into the molecular pathogenesis of F1-CH-C, we used real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to study the mRNA expression of 240 selected genes in liver tissue with F1-CH-C, in comparison with NL. The expression of 54 (22.5%) of the 240 genes was significantly different between F1-CH-C and NL; 46 genes were upregulated and 8 were downregulated in F1-CH-C. The most noteworthy changes in gene expression mainly affected the transcriptional network regulated by interferons (IFNs), including both IFN-alpha/beta-inducible genes (STAT1, STAT2, ISGF3G/IRF9, IFI27, G1P3, G1P2, OAS2, MX1) and IFN-gamma-inducible genes (CXCL9, CXCL10, CXCL11). Interesting, upregulation of IFN-alpha/beta-inducible genes (but not IFN-gamma-inducible genes) was independent of histological scores (grade and stage of fibrosis) and HCV characteristics (hepatic HCV mRNA levels and the HCV genotype), and was specific to HCV (as compared to hepatitis B virus (HBV)). Other genes dysregulated in F1-CH-C, albeit less markedly than IFN-alpha/beta- and IFN-gamma-inducible genes, were mainly involved in the activation of lymphocytes infiltrating the liver (IFNG, TNF, CXCL6, IL6, CCL8, CXCR3, CXCR4, CCR2), cell proliferation (p16/CDKN2A, MKI67, p14/ARF), extracellular matrix remodeling (MMP9, ITGA2), lymphangiogenesis (XLKD1/LYVE), oxidative stress (CYP2E1), and cytoskeleton microtubule organization (STMN2/SCG10). Thus, a limited number of signaling pathways, and particularly the transcriptional network regulated by interferons, are dysregulated in the first stage of HCV-induced liver fibrosis. Some of the genes identified here could form the basis for new approaches aimed at refining IFN-based therapies for chronic HCV infection.Virology 03/2005; 332(1):130-44. · 3.37 Impact Factor