Silvia Martina Ferrari

Università di Pisa, Pisa, Tuscany, Italy

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Publications (132)377.71 Total impact

  • [Show abstract] [Hide abstract]
    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)-γ-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-α may result in viral clearance during persistent infection and revert this process. Theoretically agents that selectively neutralize CXCL10 could increase patient responsiveness to traditional IFN-based HCV therapy. Several studies have reported IL-28B polymorphisms and circulating CXCL10 may be a prognostic markers for HCV treatment efficacy in HCV genotype 1 infection.
    Immunologic research. 11/2014;
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    ABSTRACT: Autoimmune thyroid diseases (AITD) result from a dysregulation of the immune system leading to an immune attack on the thyroid. AITD are T cell-mediated organ-specific autoimmune disorders. The prevalence of AITD is estimated to be 5%; however, the prevalence of antithyroid antibodies may be even higher. The AITD comprise two main clinical presentations: Graves' disease (GD) and Hashimoto's thyroiditis (HT), both characterized by lymphocytic infiltration of the thyroid parenchyma. The clinical hallmarks of GD and HT are thyrotoxicosis and hypothyroidism, respectively. The mechanisms that trigger the autoimmune attack to the thyroid are still under investigation. Epidemiological data suggest an interaction among genetic susceptibility and environmental triggers as the key factor leading to the breakdown of tolerance and the development of disease. Recent studies have shown the importance of cytokines and chemokines in the pathogenesis of AT and GD. In thyroid tissue, recruited T helper 1 (Th1) lymphocytes may be responsible for enhanced IFN-γ and TNF-α production, which in turn stimulates CXCL10 (the prototype of the IFN-γ-inducible Th1 chemokines) secretion from the thyroid cells, therefore creating an amplification feedback loop, initiating and perpetuating the autoimmune process. Associations exist between AITD and other organ specific (polyglandular autoimmune syndromes), or systemic autoimmune disorders (Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, cryoglobulinemia, sarcoidosis, psoriatic arthritis). Moreover, several studies have shown an association of AITD and papillary thyroid cancer. These data suggest that AITD patients should be accurately monitored for thyroid dysfunctions, the appearance of thyroid nodules, and other autoimmune disorders.
    Autoimmunity Reviews. 10/2014;
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    ABSTRACT: Hepatitis C virus (HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus (T1DM) and T2DM. T2DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2DM and chronic hepatitis C (CHC) infection. The processes through which CHC is associated with T2DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immune-mediated mechanisms. Few data have been reported on the association of CHC and T1DM and reports on the potential association between T1DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoimmunity and in certain cases lead to the development of T1DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with non-diabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effective programmes for the surveillance and treatment of diabetic CHC patients.
    World journal of diabetes. 10/2014; 5(5):586-600.
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    ABSTRACT: We report the antineoplastic and anti-angiogenic activity of the pyrazolo[3,4-d]pyrimidine derivative CLM3 and the cyclic amide CLM94, both multiple tyrosine kinase inhibitors (TKIs), in human primary medullary thyroid cancer (P-MTC) cells, and in vitro in the medullary thyroid cancer (MTC) cell lines TT (harboring a RET C634W activating mutation) and MZ-CRC-1 (carrying the MEN2B RET mutation Met891Thr).
    Surgery 08/2014; · 3.37 Impact Factor
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    ABSTRACT: IFN-γ-induced protein 10 (IP-10) and its receptor, CXCR3 chemokine (C-X-C motif) receptor 3 (CXCR3), appear to contribute to the pathogenesis of HCV related mixed cryoglobulinemia (HCV+MC). The secretion of IP-10 by CD4+, CD8+ and natural killer (NK)-T cells is dependent on interferon (IFN)-γ, which is itself mediated by the interleukin (IL)-12 cytokine family. Under the influence of IFN-γ, IP-10 is secreted by several cell types including lymphocytes, hepatocytes, endothelial cells, fibroblasts, etc. In tissues, recruited T helper (Th) 1 lymphocytes may be responsible for enhanced IFN-γ and tumor necrosis factor (TNF)-α production, which in turn stimulates IP-10 secretion from the cells, therefore creating an amplification feedback loop, and perpetuating the autoimmune process. High levels circulation of IP-10 have been found in HCV+MC, especially in patients with clinically active vasculitis. Furthermore, HCV+MC patients with autoimmune thyroiditis (AT), have higher levels than those without AT. Further studies are needed to investigate interactions between chemokines and cytokines in the pathogenesis, and to evaluate whether IP-10 is a novel therapeutic target in HCV+MC.
    La Clinica terapeutica. 07/2014; 165(4):e317-e322.
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    ABSTRACT: The interferon-γ-inducible protein 10 (IP-10) was initially identified as a chemokine that is induced by interferon (IFN)-γ. IP-10 exerts its function through binding to chemokine (C-X-C motif) receptor 3 (CXCR3). IP-10 and its receptor, CXCR3, appear to contribute to the pathogenesis of many autoimmune diseases, organ specific (such as type 1 diabetes, Graves' disease and ophthalmopathy), or systemic (such as systemic lupus erythematosus, mixed cryoglobulinemia, Sjogren syndrome, or systemic sclerosis). The secretion of IP-10 by (CD)4+, CD8+, and natural killer is dependent on IFN-γ. Under the influence of IFN-γ, IP-10 is secreted by thyrocytes. Determination of high level of IP-10 in peripheral fluids is therefore a marker of a T helper 1 orientated immune response. High levels of circulating IP-10, have been shown in patients with autoimmune thyroiditis (AT). Among patients with AT, IP-10 levels were significantly higher in those with a hypoechoic ultrasonographic pattern, which is a sign of a more severe lympho-monocytic infiltration, and in those with hypothyroidism. For these reasons, it has been postulated that IP-10 could be a marker of a stronger and more aggressive inflammatory response in the thyroid, subsequently leading to thyroid destruction and hypothyroidism. Further studies are needed to investigate whether IP-10 is a novel therapeutic target in AT.
    06/2014;
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    ABSTRACT: An increasing body of evidence shows the importance of the chemokine (C-X-C motif) receptor (CXCR)3 and cognate chemokines (C-X-C motif) ligand (CXCL)9, CXCL10 and CXCL11 in the T helper 1 immune response, and in inflammatory diseases such as bowel inflammatory disorders, allograft rejection, thyroid autoimmune disorders, vascular and renal inflammation, and others. Peroxisome proliferator-activated receptor (PPAR)-γ agonists show a strong inhibitory effect on the expression and production of CXCR3 chemokines in vitro, in various kinds of cells, such as denditric cells, monocytes, macrophages, endothelial and vascular smooth muscle cells, intestinal cells, thyrocytes, fibroblasts, preadypocytes and mesangial cells, and in vivo in animal models. As rosiglitazone has recently been linked to a higher risk of heart failure, stroke, and all-cause mortality in old patients, it has been interrupted from the European market. On the contrary, the safety profile of pioglitazone seems favorable. However, further studies are ongoing to explore the use of new PPAR-γ agonists in the treatment of the above mentioned inflammatory disorders, and many interesting patents have been recently applied.
    Recent Patents on Inflammation & Allergy Drug Discovery 06/2014;
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    ABSTRACT: The C-X-C chemokine receptor (CXCR)3 and its chemokines (CXCL9, CXCL10, CXCL11) are involved in the pathogenesis of autoimmune thyroiditis (AT), Graves' disease (GD) and Graves' Ophthalmopathy (GO). Under the influence of interferon(IFN)γ, the IFNγ-induced protein 10 (IP-10/CXCL10) is secreted by thyrocytes, orbital fibroblasts and preadipocytes. In tissue, Th1 lymphocytes are recruited, hence IFNγ is enhanced, which stimulates CXCL10 secretion reiterating the autoimmune process. The presence of elevated levels of CXCL10 in peripheral liquids is considered a marker of Th1 orientated immune response. High levels of circulating CXCL10 (sCXCL10) have been shown in patients with AT, overall with hypothyroidism. In GD and GO patients high sCXCL10 have been shown particularly in the active disease. A modulatory role of peroxisome proliferator-activated receptor(PPAR)γ or -α agonists on CXCR3 chemokines in AT, GD and GO and the immuno-modulatory effect of methimazole on CXCR3 chemokines in GD have been shown. Further studies are ongoing to explore the use of new molecules that act as antagonists of CXCR3, or block CXCL10, in autoimmune disorders, and many interesting patents have been recently applied.
    Recent Patents on Endocrine Metabolic & Immune Drug Discovery 06/2014;
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    ABSTRACT: It has been frequently reported a higher incidence of psychotic disorders in immigrants than in native populations. There is, however, a lack of knowledge about risk factors which may explain this phenomenon. A better understanding of the causes of psychosis among first-generation migrants is highly needed, particularly in Italy, a country with a recent massive migration.
    BMC Psychiatry 06/2014; 14(1):186. · 2.23 Impact Factor
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    ABSTRACT: Although generally the prognosis of differentiated thyroid carcinoma (DTC) is good, approximately 5% of people are likely to develop metastases which fail to respond to radioactive iodine, and other traditional therapies, exhibiting a more aggressive behavior. Nowadays, therapy is chosen and implemented on a watch-and-wait basis for most DTC patients. Which regimen is likely to work best is decided on the basis of an individual's clinical information, but only data referring to outcomes of groups of patients are employed. To predict the best course of therapy, an individual patient's biologic data is rarely employed in a systematic way. Anyway, the use of not expensive individual genomic analysis could lead us to a new era of patient-specific and personalized care. Recently, key targets that are now being evaluated in the clinical setting have been evidenced in the pathogenesis of these diseases. Some of the known genetic alterations playing a crucial role in the development of thyroid cancer include B-Raf gene mutations, rearranged during transfection/ papillary thyroid carcinoma gene rearrangements, and vascular endothelial growth factor receptor-2 angiogenesis pathways. The development of targeted novel compounds able to induce clinical responses and stabilization of disease has overcome the lack of effective therapies for DTC, which are resistant to radioiodine and thyroid stimulating hormone-suppressive therapy. Interestingly, the best responses have been demonstrated in patients treated with anti-angiogenic inhibitors such as vandetanib and XL184 in medullary thyroid cancer, and sorafenib in papillary and follicular DTC.
    Current genomics. 06/2014; 15(3):190-202.
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    ABSTRACT: The chemokine (C-X-C motif) ligand 10 (CXCL10, also called IP-10) was initially identified as a chemokine that is induced by interferon (IFN)-γ. CXCL10 exerts its function through binding to chemokine (C-X-C motif) receptor 3 (CXCR3). CXCL10 and its receptor, CXCR3, appear to contribute to the pathogenesis of many autoimmune diseases, organ specific (such as type 1 diabetes, Graves' disease and ophthalmopathy), or systemic (such as systemic lupus erythematosus, mixed cryoglobulinemia, Sjogren syndrome, or systemic sclerosis). The secretion of CXCL10 by CD4+, CD8+, and natural killer is dependent on IFN-γ. Under the influence of IFN-γ, CXCL10 is secreted by thyrocytes. Determination of high level of CXCL10 in peripheral fluids is therefore a marker of a T helper 1 orientated immune response. High levels of circulating CXCL10, have been shown in patients with autoimmune thyroiditis (AT). Among patients with AT, CXCL10 levels were significantly higher in those with a hypoechoic ultrasonographic pattern, that is a sign of a more severe lympho-monocytic infiltration, and in those with hypothyroidism. For these reasons it has been postulated that CXCL10 could be a marker of a stronger and more aggressive inflammatory response in the thyroid, subsequently leading to thyroid destruction and hypothyroidism. Further studies are needed to investigate whether CXCL10 is a novel therapeutic target in AT.
    La Clinica terapeutica. 05/2014; 165(3):e237-e242.
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    ABSTRACT: Systemic sclerosis (SSc) is a connective tissue disease associated with increased functional impairment, body image distress due to skin lesions, and psychosocial comorbidity, particularly depression. Prevalence of depressive symptoms in SSc patients ranges from 36% to 65% and it contributes to the worsening of any aspect of the disease. The aim of this study was to investigate the prevalence and clinical and non-clinical correlates of depressive symptoms in a sample of outpatients with SSc. Seventy-eight consecutive SSc outpatients were recruited from February 2005 to July 2007. Socio-demographic and SSc-related clinical data were collected, including a modified Rodnan Skin Score, the Valentini Disease Activity Index and psycho-metric assessment of disability and pain. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Two questions on perception of support from relatives and impact of disfigurements were also directly addressed to subjects. The BDI mean score was 10.5 (± 8.3), with 36 subjects (46.2%) scoring above clinical significance. Unemployment, increased disability, pain, disease activity and articular involvement were significantly associated with more depressive symptoms. Older age, unemployment and more depressive symptoms were also related with complaints of disfigurements due to skin involvement. Depression is an influential prognostic factor in SSc. The present study contributes to the knowledge of the relationship between depression and clinical features routinely collected in rheumatology settings in order to develop a standardized assessment of psychosocial distress in routine rheumatologic procedures.
    International Journal of Rheumatic Diseases 02/2014; 17(2):186-94. · 1.65 Impact Factor
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    ABSTRACT: To report on the effects on health that the 2008 Great Recession is producing in Italy, by comparing the consistency of Italian data with general observations reported in the scientific literature, and by pointing out consequences on the rates of all-cause mortality, cardiovascular mortality, male suicidal behaviours, daytime alcohol drinking and traffic fatalities. This is an ecological study in which MEDLINE, PsycINFO and PubMed were searched for the literature with combinations of the following keywords: economic recession, financial crisis, unemployment, health, suicide and mental health. Data from two Italian government agencies (Italian Institute of Statistics, ISTAT, and Italian Agency of Drugs, AIFA) in the years from 2000 to 2010 were obtained and analysed, by producing models of multiple linear regressions. After the recession onset, all-cause mortality remained stable, and was not associated with the economic fluctuations. Differently, cardiovascular mortality was associated with the rate of unemployment, and showed a significant increase in 2010. Alcohol consumption increased in 2009, the year with the worst real GDP decrease (-5.1 %). Though the total rate of suicide was not associated with the economic situation, male completed and attempted suicides due to financial crisis were significantly associated with the rate of unemployment and the real GDP. The increasing diffusion of antidepressants was not associated with a lowering of the rate of suicide. The data on the Italian situation here discussed are sufficiently reliable to conclude that a link exists between the ongoing economic recession and health and mental health of Italians. Further research is needed to understand more in detail and with stronger reliability such link, to support primary and secondary preventive interventions and orient the development of effective sociopolitical interventions.
    Social Psychiatry 01/2014; · 2.05 Impact Factor
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    ABSTRACT: Recruitment to psychiatry is insufficient to meet projected mental health service needs world-wide. We report on the career plans of final year medical students from 20 countries, investigating factors identified from the literature which influence psychiatric career choice. Cross sectional electronic or paper survey. Subjects were final year medical students at 46 medical schools in participating countries. We assessed students' career intentions, motivations, medical school teaching and exposure to psychiatry. We assessed students' attitudes and personality factors. The main outcome measure was likelihood of specializing in psychiatry. Multilevel logistic regression was used to examine the joint effect of factors upon the main outcome. 2198 of 9135 (24%) of students responded (range 4 to 91%) across the countries. Internationally 4.5% of students definitely considered psychiatry as a career (range 1 to 12%). 19% of students (range 0 to 33%) were "quite likely", and 25% were "definitely not" considering psychiatry. Female gender, experience of mental/physical illness, media portrayal of doctors, and positive attitudes to psychiatry, but not personality factors, were associated with choosing psychiatry. Quality of psychiatric placement (correlation coefficient = 0.22, p < 0.001) and number of placements (correlation coefficient =0.21, p < 0.001) were associated with higher ATP scores. During medical school, experience of psychiatric enrichment activities (special studies modules and university psychiatry clubs), experience of acutely unwell patients and perceived clinical responsibility were all associated with choice of psychiatry.Multilevel logistic regression revealed six factors associated with students choosing psychiatry: importance of own vocation, odds ratio (OR) 3.01, 95% CI 1.61 to 5.91, p < 0.001); interest in psychiatry before medical school, OR 10.8 (5.38 to 21.8, p < 0.001); undertaking a psychiatry special study module, OR 1.45 (1.05 to 2.01, p = 0.03) or elective OR 4.28 (2.87- 6.38, p < 0.001); membership of a university psychiatry club, OR 3.25 (2.87 to 6.38, p < 0.001); and exposure to didactic teaching, OR 0.54 (0.40 to 0.72, p < 0.001). We report factors relevant to medical student selection and psychiatry teaching which affect career choice. Addressing these factors improve recruitment to psychiatry internationally.
    BMC Medical Education 01/2014; 14(1):12. · 1.41 Impact Factor
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    ABSTRACT: Context and Objective. We have studied the antitumor activity of a "pyrazolo[3,4-d]pyrimidine" compound (CLM3) proposed for a multiple signal transduction inhibition [including the RET tyrosine kinase, epidermal growth factor receptor, vascular endothelial growth factor (VEGF) receptor (VEGFR) and with antiangiogenic activity], in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer) and in an ATC-cell line (AF). Design and Main Outcome Measures. CLM3 was tested: in primary ATC cells at the concentrations of 5, 10, 30, 50 μM; in 8305C cells, and in AF cells, at 1, 5, 10, 30, 50 or 100 μM; in AF cells in CD nu/nu mice. Results. CLM3 significantly inhibited proliferation of 8305C and AF cells, inducing also apoptosis. A significant reduction of proliferation with CLM3 in ATC cells (P < 0.01, ANOVA) was shown. CLM3 increased the percentage of apoptotic ATC cells dose-dependently (P < 0.001, ANOVA) and inhibited migration (P < 0.01) and invasion (P < 0.001). AF-cell line was injected sc in CD nu/nu mice and tumor masses became detectable 15 days after. CLM3 (50 mg/kg/die) inhibited significantly tumor growth (starting 16 days after the beginning of treatment). CLM3 significantly decreased the VEGF-A expression and microvessel density in AF tumor tissues. Furthermore, CLM3 inhibited EGFR, AKT and ERK1/2 phosphorylation and down-regulated cyclin D1 in 8305C and AF cells. Conclusions. The antitumor and antiangiogenic activity of a "pyrazolo[3,4-d]pyrimidine" compound (CLM3) is very promising in anaplastic thyroid cancer, opening the way to a future clinical evaluation.
    The Journal of Clinical Endocrinology and Metabolism 01/2014; · 6.31 Impact Factor
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    ABSTRACT: The prevalence and clinical features of thyroid involvement in patients with hepatitis C virus-associated mixed cryoglobulinemia (MC+HCV) have been reviewed. A PubMed Medline search was conducted through December 2011 to identify all studies that reported thyroid involvement in MC+HCV patients. Reference lists of the papers initially detected were manually searched to identify additional relevant reports. Studies had to contain sufficient and clear information to be included. In MC+HCV patients, the following thyroid autoimmune abnormalities were significantly more frequent than in controls: high levels of serum anti-thyroperoxidase autoantibody (AbTPO); high levels of serum AbTPO and/or anti-thyroglobulin autoantibody; humoral and ultrasonographical signs of thyroid autoimmunity (35% vs 16%); prevalence of subclinical hypothyroidism (11% vs 2%). Also, the prevalence of papillary thyroid cancer has been found higher in MC+HCV patients than in controls, in particular in patients with autoimmune thyroiditis. The involvement of T helper 1 immunity and chemokine (C-X-C motif) ligand 10 (CXCL10) may be the pathogenetic basis of the association between MC+HCV and thyroid autoimmunity. These results show a high prevalence of thyroid disorders in patients with MC+HCV and point to the need for careful monitoring of thyroid function in these patients.
    Hormones (Athens, Greece) 01/2014; 13(1):16-23. · 2.01 Impact Factor
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    ABSTRACT: Introduction: Recently, tyrosine kinase inhibitors (TKIs) have emerged as a new class of anticancer therapy. Although generally considered less toxic than cytotoxic chemotherapy, TKIs do cause significant side effects including fatigue and hypertension. In addition, thyroid dysfunction is a well-known adverse effect of TKI. Areas covered: This review provides a comprehensive assessment of TKI-induced thyroid dysfunctions by sunitinib, sorafenib, pazopanib, imatinib, dasatinib, nilotinib, vandetanib, axitinib, motesanib and tivozanib. Furthermore, the potential mechanisms that result in this toxicity, the clinical impact of thyroid dysfunction in these patients and the controversies regarding treatment with thyroid hormone (TH) therapy are evaluated. Expert opinion: Detection of TKI-induced thyroid dysfunction requires routine monitoring of thyroid function and may necessitate treatment. Potential benefits in developing thyroid dysfunction and potential harm in treating it necessitate controlled studies. Finally, if treatment is pursued, appropriate dosing and timing of TH replacement will require prospective clinical evaluation.
    Expert Opinion on Drug Safety 01/2014; 13(6). · 2.74 Impact Factor
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    ABSTRACT: Frequently, patients with hepatitis C virus (HCV) chronic infection have high levels of serum anti-thyroperoxidase and/or anti-thyroglobulin autoantibodies, ultrasonographic signs of chronic autoimmune thyroiditis, and subclinical hypothyroidism, in female gender versus healthy controls, or hepatitis B virus infected patients. In patients with "HCV-associated mixed cryoglobulinemia" (MC + HCV), a higher prevalence of thyroid autoimmune disorders was shown not only compared to controls, but also versus HCV patients without cryoglobulinemia. Patients with MC + HCV or HCV chronic infection show a higher prevalence of papillary thyroid cancer than controls, in particular in patients with autoimmune thyroiditis. Patients with HCV chronic infection, or with MC + HCV, in presence of autoimmune thyroiditis, show higher serum levels of T-helper (Th)1 (C-X-C motif) ligand 10 (CXCL10) chemokine, but normal levels of Th2 (C-C motif) ligand 2 chemokine, than patients without thyroiditis. HCV thyroid infection could act by upregulating CXCL10 gene expression and secretion in thyrocytes recruiting Th1 lymphocytes that secrete interferon-γ and tumor necrosis factor-α. These cytokines might induce a further CXCL10 secretion by thyrocytes, thus perpetuating the immune cascade, which may lead to the appearance of autoimmune thyroid disorders in genetically predisposed subjects. A careful monitoring of thyroid function, particularly where nodules occur, is recommended in HCV patients.
    International journal of endocrinology. 01/2014; 2014:935131.
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    ABSTRACT: Type 1 diabetes (T1D) is due to antigen-specific assaults on the insulin producing pancreatic β-cells by diabetogenic T-helper (Th)1 cells. (C-X-C motif) ligand (CXCL)10, an interferon-γ inducible Th1 chemokine, and its receptor, (C-X-C motif) receptor (CXCR)3, have an important role in different autoimmune diseases. High circulating CXCL10 levels were detected in new onset T1D patients, in association with a Th1 autoimmune response. Furthermore β-cells produce CXCL10, under the influence of Th1 cytokines, that suppresses their proliferation. Viral β-cells infections induce cytokines and CXCL10 expression, inducing insulin-producing cell failure in T1D. CXCL10/CXCR3 system plays a critical role in the autoimmune process and in β-cells destruction in T1D. Blocking CXCL10 in new onset diabetes seems a possible approach for T1D treatment.
    Cytokine & growth factor reviews 01/2014; · 6.49 Impact Factor
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    ABSTRACT: To our knowledge, no study has evaluated the involvement of T helper (Th)1- and Th2-chemokines in extra-ocular muscle (EOM) myopathy in “patients with thyroid-associated ophthalmopathy” (TAO-p). We tested the effects of interferon (IFN)γ and tumor necrosis factor (TNF)α stimulation, and of increasing concentrations of peroxisome proliferator-activated receptor (PPAR)γ agonists (pioglitazone or rosiglitazone; 0.1 μM–20 μM), on Th1-chemokine [C-X-C motif ligand (CXCL)10] and Th2-chemokine [C-C motif ligand (CCL)2] secretion in primary EOM cultures from TAO-p vs. control myoblasts. Moreover, we evaluated serum CXCL10 and CCL2 in active TAO-p with prevalent EOM involvement (EOM-p) vs. those with prevalent orbital fat expansion (OF-p). Serum CXCL10 was higher in OF-p and EOM-p vs. controls, while serum CCL2 was not significantly different in controls, or in OF-p and EOM-p. We showed the expression of PPARγ in EOM cells. In primary EOM cultures from TAO-p: a) CXCL10 was undetectable in the supernatant, IFNγ dose-dependently induced it, whereas TNFα did not; b) EOM produced basally low amounts of CCL2, TNFα dose-dependently induced it, whereas IFNγ did not; c) the combination of TNFα and IFNγ had a significant synergistic effect on CXCL10 and CCL2 secretion; and d) PPARγ agonists have an inhibitory role on the modulation of CXCL10, while they stimulate CCL2 secretion. EOM participates in the self-perpetuation of inflammation by releasing both Th1 (CXCL10) and Th2 (CCL2) chemokines under the influence of cytokines, in TAO. PPARγ agonist activation plays an inhibitory role on CXCL10, but stimulates the release of CCL2.
    Autoimmunity Reviews. 01/2014;

Publication Stats

1k Citations
377.71 Total Impact Points

Institutions

  • 2004–2014
    • Università di Pisa
      • Department of Clinical and Experimental Medicine
      Pisa, Tuscany, Italy
    • Università degli Studi di Modena e Reggio Emilia
      • Department of Biomedical, Metabolical and Neurosciences
      Modène, Emilia-Romagna, Italy
  • 2009–2011
    • University of Bologna
      • Institute of Psychiatry "P. Ottonello"
      Bologna, Emilia-Romagna, Italy
  • 2005–2011
    • National Research Council
      • Institute of Clinical Physiology IFC
      Roma, Latium, Italy