Circulating CXCL11 and CXCL10 are increased in hepatitis C-associated cryoglobulinemia in the presence of autoimmune thyroiditis
Department of Internal Medicine, University of Pisa, School of Medicine, Via Roma, 67, 56100, Pisa, Italy, . Modern Rheumatology
(Impact Factor: 2.4).
12/2011; 22(5):659-67. DOI: 10.1007/s10165-011-0565-x
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.
Available from: Anna Linda Zignego
- "This chemokine, also known as BCA-1 (B-cell-attracting chemokine-1) or BLC (B-lymphocyte chemoattractant), is a major regulator of B-cell trafficking, and its expression has been found to be significantly enhanced in microdissected samples from liver biopsy of patients with active cutaneous vasculitis. Antonelli and coworkers showed that serum concentrations of different cytokines and chemokines are significantly modified in MC patients  and have recently investigated the potential role of CXCL-10 and CXCL-11 in the pathogenesis of MC [61, 62]. In fact, high serum concentration of these soluble factors has been shown in HCV patients with MC when compared to patients without MC and healthy controls. "
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ABSTRACT: Hepatitis C virus (HCV) infection is a serious public health problem because of its worldwide diffusion and sequelae. It is not only a hepatotropic but also a lymphotropic agent and is responsible not only for liver injury--potentially evolving to cirrhosis and hepatocellular carcinoma--but also for a series of sometimes severely disabling extrahepatic diseases and, in particular, B-cell lymphoproliferative disorders. These latter range from benign, but prelymphomatous conditions, like mixed cryoglobulinemia, to frank lymphomas. Analogously with Helicobacter pylori related lymphomagenesis, the study of the effects of viral eradication confirmed the etiopathogenetic role of HCV and showed it is an ideal model for better understanding of the molecular mechanisms involved. Concerning these latter, several hypotheses have been proposed over the past two decades which are not mutually exclusive. These hypotheses have variously emphasized the important role played by sustained stimulation of the immune system by HCV, infection of the lymphatic cells, viral proteins, chromosomal aberrations, cytokines, or microRNA molecules. In this paper we describe the main hypotheses that have been proposed with the corresponding principal supporting data.
Clinical and Developmental Immunology 07/2012; 2012(5):980942. DOI:10.1155/2012/980942 · 2.93 Impact Factor
Available from: Alessandro Antonelli
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ABSTRACT: Cytokines are intercellular mediators involved in viral control and liver damage being induced by infection with hepatitis C virus (HCV). The complex cytokine network operating during initial infection allows a coordinated, effective development of both innate and adaptive immune responses.
However, HCV interferes with cytokines at various levels and escapes immune response by inducing a T-helper (Th)2/T cytotoxic 2 cytokine profile. Inability to control infection leads to the recruitment of inflammatory infiltrates into the liver parenchyma by interferon (IFN)-gamma-inducible CXC chemokine ligand (CXCL)-9, -10, and -11 chemokines, which results in sustained liver damage and eventually in liver cirrhosis. The most important systemic HCV-related extrahepatic diseases—mixed cryoglobulinemia, lymphoproliferative disorders, thyroid autoimmune disorders, and type 2 diabetes—are associated with a complex dysregulation of the cytokine/chemokine network, involving proinflammatory and Th1 chemokines. The therapeutical administration of cytokines such as IFN-alpha may result in viral clearance during persistent infection and reverts this process.
Clinical and Developmental Immunology 05/2012; 2012(2, supplement):468107. DOI:10.1155/2012/468107 · 2.93 Impact Factor
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ABSTRACT: Until now, no study has evaluated CXCL9 in hepatitis C virus (HCV) infection-related mixed cryoglobulinemia (MC) patients in presence/absence of autoimmune thyroiditis (AT). Serum CXCL9 and CXCL10 have been measured in 60 patients with MC (MCo), in 35 patients with MC and AT (MC-AT), in sex and age-matched controls: 60 healthy (Control 1); 35 patients with AT without cryoglobulinemia (Control 2). CXCL9 and CXCL10 were higher in MC-AT patients than Control 2 (P<0.0001) and MCo (P=0.01), in MCo than Control 1 (P<0.0001), and in Control 2 than Control 1 (P<0.001). By defining a high CXCL9 level as a value>2 SD above the mean value of the Control 1 (>122 pg/mL), 5% of Control 1, 34% of Control 2, 91% of MCo, and 97% of MC+AT had high CXCL9 (P<0.0001, chi-square). By simple regression analysis CXCL9 and CXCL10 were related to each other in MCo (r=0.426, P=0.001) and in MC-AT (r=0.375, P=0.001). We first demonstrate high serum levels of CXCL9 in cryoglobulinemic patients, especially with AT. Further, a strong association between serum CXCL9 and CXCL10 has been observed in patients with MC in presence/absence of AT.
Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 07/2013; 33(12). DOI:10.1089/jir.2012.0091 · 2.00 Impact Factor
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