Daniela Ferrari

HCV-related autoimmune and neoplastic disorders: the HCV syndrome

Hepatitis C virus (HCV) chronic infection may be associated with a great number of both hepatic and extrahepatic manifestations. HCV lymphotropism is responsible for poly-oligoclonal B-lymphocyte expansion, which is the common underlying alteration in a significant percentage of HCV-infected individuals. The consequent production of different autoantibodies and immune-complexes, including cryoglobulins, may lead to organ- and non-organ-specific immunological alterations. Mixed cryoglobulinemia, a small-vessel systemic vasculitis, is characterized by the coexistence of autoimmune and lymphoproliferative alterations; therefore, it represents the prototype of HCV-associated disorders. Moreover, HCV shows an oncogenic potential; several studies support its pathogenetic link with some malignancies, mainly hepatocellular carcinoma and B-cell lymphomas. On the whole, HCV-related disorders present a heterogeneous geographical distribution, suggesting a role of other important genetic and/or environmental cofactors. While the majority of HCV-infected individuals is asymptomatic or may develop only liver manifestations, a significant percentage of them may develop a variable combination of autoimmune lymphoproliferative disorders. The resulting multiform clinico-pathological condition can be termed HCV syndrome. The natural history of HCV syndrome is the expression of multifactorial and multistep pathogenetic process, which usually proceeds from mild, often isolated manifestations to systemic immune-mediated disorders, and less frequently to overt malignancies.

High Values of CXCL10 Serum Levels in Mixed Cryoglobulinemia Associated With Hepatitis C Infection

OBJECTIVES:No study has evaluated circulating CXCL10 in patients with mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) chronic infection. The aim of this study is to measure inteferon-inducible protein 10 (CXCL10/IP-10), interferon-gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) (Th1 cytokines) in a series of cryoglobulinemic patients and to correlate this parameter to the clinical phenotype.METHODS:Serum CXCL10, IFN-gamma, and TNF-alpha were assayed in 102 patients with hepatitis C-associated cryoglobulinemia (MC + HCV), in 102 sex- and age-matched patients with type C chronic hepatitis without cryoglobulinemia (HCV+), and in 102 sex- and age-matched controls.RESULTS:Cryoglobulinemic patients showed significantly higher mean CXCL10 serum levels than controls (P < 0.0001) or HCV+ patients (P < 0.0001) (397 ± 132 pg/mL, 92 ± 53 pg/mL, 280 ± 149 pg/mL, respectively). Moreover, CXCL10 was significantly increased in 30 cryoglobulinemic patients with active vasculitis compared to those without it (460 ± 104 pg/mL vs 369 ± 139 pg/mL, respectively; P < 0.001). Both groups of MC + HCV patients with or without active vasculitis had serum CXCL10 significantly higher than HCV+ patients (P < 0.001, P= 0.02, respectively). IFN-gamma levels were not significantly different in MC + HCV than in HCV+ patients or controls. Serum TNF-alpha levels were significantly higher in MC + HCV than in HCV+ patients or controls (median [interquartile range]: 12.0 [9.8], 5.7 [5.4], 1.3 [2.1] pg/mL, respectively; P < 0.0001).CONCLUSIONS:The study demonstrates high CXCL10 and TNF-alpha serum levels in patients with hepatitis C-associated cryoglobulinemia. Moreover, in MC + HCV patients, increased CXCL10 levels were significantly associated with the presence of active vasculitis.

Differentiation-dependent lysine 4 acetylation enhances MEF2C binding to DNA in skeletal muscle cells

Myocyte enhancer factor 2 (MEF2) proteins play a key role in promoting the expression of muscle-specific genes in differentiated muscle cells. MEF2 activity is regulated by the association with several transcriptional co-factors and by post-translational modifications. In the present report, we provide evidence for a novel regulatory mechanism of MEF2C activity, which occurs at the onset of skeletal muscle differentiation and is based on Lys4 acetylation. This covalent modification results in the enhancement of MEF2C binding to DNA and chromatin. In particular, we report that the kinetic parameters of MEF2/DNA association change substantially upon induction of differentiation to give a more stable complex and that this effect is mediated by Lys4 acetylation. We also show that Lys4 acetylation plays a prominent role in the p300-dependent activation of MEF2C.

Correlation of articular involvement, skin disfigurement and unemployment with depressive symptoms in patients with systemic sclerosis: a hospital sample

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.

THU0246 Psychiatric disorders in rheumatology: Evaluation of a screening protocol in 100 hospitalized patients

Background Psychiatric disorders, namely depression (D) and anxiety (A) can frequently occur in course of chronic rheumatic diseases. These comorbidities remain often misdiagnosed and consequently not correctly treated. Objectives Aims of our study are to evaluate the frequency of D and A in a hospitalized sample of rheumatic patients, and to test the efficacy of a screening by mean of questionnaires to detect D and A. Methods 100 consecutive patients affected by rheumatic diseases were evaluate using the Italian version of Beck Depression Inventory (BDI) and the Sheehan Patient Rated Anxiety Scale (SPRAS). Furthermore, a clinical psychiatric evaluation was performed by rheumatologist’s decision or when questionnaires were positive. Results Of 100 patients studied 28% were affected by arthritis, 38% by connective tissue disease, 22% by vasculitis, 12% by miscellanea. Mean age was 57.2±11.4 years, 82% were females, 68% were married, 10.4% lived alone, 11.2% were unable to work because of their disease, 29.4% underwent a psychopharmacological therapy at the moment of the hospitalization. BDI score was suggestive for D (>17) in 17/100 (17%), but only in 12/100 (12%) D was confirmed by psychiatris evaluation; in the same way, SPRAS score was suggestive for A (>30) in 21/100 (21%) and the diagnosis was confirmed by the psychiatrist in 16/100 (16%). On the whole, 31 psychiatric visits were performed (18 because of questionnaires, 9 after rheumatologist’s prescription + questionnaires, 4 after rheumatologist’s prescription only); D and/or A was diagnosed in 22/100 (22%) and an appropriate psychopharmacological therapy was consequently prescribed (78% SSRI + BDZ). Conclusions Depression and anxiety were frequently detected in our population, with a percentage respectively of 12% and 16%. A screening performed using questionnaires is useful to identify a psychiatric comorbidity in these patients; in fact, in our study it proved to have an higher sensitivity than the only rheumatologic evaluation. Nevertheless, because of the presence of false positive results, a psychiatric visit is always necessary to confirm the diagnosis. Disclosure of Interest None Declared