Inhibitory Receptors and Pathways of Lymphocytes: The Role of PD-1 in Treg Development and Their Involvement in Autoimmunity Onset and Cancer Progression

Regulatory T (Treg) cells represent a subpopulation of suppressor CD4+ T cells critically involved in the establishment of peripheral tolerance through the inhibition of effector T (Teff) cells and the suppression of the immune-mediated tissue destruction toward self-antigens. Treg generation, their suppressive properties and also Treg-Teff cell interactions could be modulated at least in part by programmed cell death-1 (PD-1) expression on their surface and through binding between PD-1 and programmed cell death ligand-1 (PD-L1). Defects involving PD-1 and Tregs can lead to the development of pathological conditions, including autoimmune disorders or promote cancer progression by favoring tumor evasion from the host immune response. At the same time, PD-1 and Tregs could represent attractive targets for treatment, as demonstrated by the therapeutic blockade of PD-L1 applied for the management of different cancer conditions in humans. In the present Review, we focus specifically the role of PD-1/PD-L1 on Treg development and activity

Influenza vaccines: Evaluation of the safety profile

3noopenThe safety of vaccines is a critical factor in maintaining public trust in national vaccination programs. Vaccines are recommended for children, adults and elderly subjects and have to meet higher safety standards, since they are administered to healthy subjects, mainly healthy children. Although vaccines are strictly monitored before authorization, the possibility of adverse events and/or rare adverse events cannot be totally eliminated. Two main types of influenza vaccines are currently available: parenteral inactivated influenza vaccines and intranasal live attenuated vaccines. Both display a good safety profile in adults and children. However, they can cause adverse events and/or rare adverse events, some of which are more prevalent in children, while others with a higher prevalence in adults. The aim of this review is to provide an overview of influenza vaccine safety according to target groups, vaccine types and production methods.openTrombetta, Claudia Maria*; Gianchecchi, Elena; Montomoli, EmanueleTrombetta, Claudia Maria; Gianchecchi, Elena; Montomoli, Emanuel

Analysis of the autoimmune regulator gene in patients with autoimmune non-APECED polyendocrinopathies

AbstractThe pathogenesis of autoimmunity was derived from a complex interaction of genetic and environmental factors. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is a rare autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene. AIRE gene variants and, in particular, heterozygous loss-of-function mutations were also discovered in organ-specific autoimmune disorders, possibly contributing to their etiopathogenesis. It was suggested that even predisposition to develop certain autoimmune conditions may be derived from AIRE gene polymorphisms including S278R and intronic IVS9+6 G>A. In this study we unravel the hypothesis on whether AIRE gene variants may predispose individuals to associated autoimmune conditions in 41 Italian patients affected by non-APECED autoimmune polyendocrinopathies. We could not detect any heterozygous mutations of the AIRE gene. Although a trend of association was observed, heterozygous polymorphisms S278R and IVS9+6 G>A were detected in patients without statistically significant prevalence than in controls. Their putative contribution to autoimmune polyendocrinopathies and their predictive value in clinical strategies of disease development could be unravelled by analysing a larger sample of diseased patients and healthy individuals

Comparative analysis of influenza A(H3N2) virus hemagglutinin specific IgG subclass and IgA responses in children and adults after influenza vaccination

AbstractTwo different influenza vaccines are generally used in many countries; trivalent live attenuated influenza vaccine (LAIV3) and trivalent inactivated influenza vaccine (IIV3). Studies comparing the antibody response to IIV3 and LAIV3 commonly investigate the seroprotective response by hemagglutination-inhibition (HI) assay. However, there is limited data regarding comparative analysis of IgG subclass and IgA responses induced by LAIV3 and IIV3.Fifteen children <5years received 2 doses of LAIV3 while 14 children aged 10–17years received one dose. In addition, 15 adults were vaccinated with either intranasal LAIV3 or intramuscular IIV3. We analyzed the H3N2 humoral responses by HI assay and the hemagglutinin (HA) specific IgG1, IgG2, IgG3, IgG4 and IgA1 responses by ELISA. Furthermore, we investigated the avidity of induced IgG antibodies.Pre-existing seroprotective HI antibodies were present in adults (73%) previously vaccinated with IIV3. Vaccination resulted in a significant increase in HI titers in all groups, except LAIV3 vaccinated adults. Furthermore, a negative correlation between age and HI titers in LAIV3 vaccinated subjects was observed post-vaccination. LAIV3 in children and IIV3 in adults induced HA-specific IgG1, low IgG3 but no IgG2 or IgG4. Moreover, significant IgA1 responses were only induced in children. Interestingly, IIV3 and LAIV3 induced IgG antibodies with comparable and significantly augmented avidity post-vaccination in children and adults.Our results suggest that age and/or exposure history play a significant role in determining the antibody response.Clinical trial registry: ClinicalTrials.gov NCT01003288 and NCT0186654

環境管理計画への市民参加とその規定因としてのエンパワーメント

<p>DMPC/2/siRNA treatment of Jurkat T cells, 48 hours from the beginning of transfection.</p

Sea buckthorn bud extract displays activity against cell-cultured Influenza virus

Introduction - Vaccines and antiviral drugs are the most widely used methods of preventing or treating Influenza virus infection. The role of sea buckthorn (SBT) bud dry extract as a natural antiviral drug against Influenza was investigated.Methods - Influenza virus was cultured in the MDCK cell line, with or without SBT bud extract, and virus growth was assessed by HA and TCID50 virus titration in terms of cytopathic effect on cells. Several concentrations of extract were tested, the virus titer being measured on day 4 after infection.Results - After infection, the virus titer in the control sample was calculated to be 2.5 TCID50/ml; treatment with SBT bud extract reduced the virus titer to 2.0 TCID50/ml at 50 µg/ml, while the HA titer was reduced from 1431 (control) to 178. Concentrations lower than 50 µg/ml displayed an inhibitory effect in the HA assay, but not in the TCID50 virus titration; however, observation of the viral cultures confirmed a slowdown of viral growth at all concentrations.Discussion - Natural dietary supplements and phytotherapy are a growing market and offer new opportunities for the treatment of several diseases and disorders. These preliminary experiments are the first to show that SBT bud extract is able to reduce the growth of the Influenza A H1N1 virus in vitro at a concentration of 50 µg/ml. This discovery opens up the possibility of using SBT bud extract as a valid weapon against Influenza and, in addition, as the starting-point for the discovery of new drugs

Sea buckthorn bud extract displays activity against cell-cultured Influenza virus

Introduction: Vaccines and antiviral drugs are the most widely used methods of preventing or treating Influenza virus infection. The role of sea buckthorn (SBT) bud dry extract as a natural antiviral drug against Influenza was investigated. Methods: Influenza virus was cultured in the MDCK cell line, with or without SBT bud extract, and virus growth was assessed by HA and TCID50 virus titration in terms of cytopathic effect on cells. Several concentrations of extract were tested, the virus titer being measured on day 4 after infection. Results: After infection, the virus titer in the control sample was calculated to be 2.5 TCID50/ml; treatment with SBT bud extract reduced the virus titer to 2.0 TCID50/ml at 50 μg/ml, while the HA titer was reduced from 1431 (control) to 178. Concentrations lower than 50μg/ml displayed an inhibitory effect in the HA assay, but not in the TCID50 virus titration; however, observation of the viral cultures confirmed a slowdown of viral growth at all concentrations. Discussion: Natural dietary supplements and phytotherapy are a growing market and offer new opportunities for the treatment of several diseases and disorders. These preliminary experiments are the first to show that SBT bud extract is able to reduce the growth of the Influenza A H1N1 virus in vitro at a concentration of 50 μg/ml. This discovery opens up the possibility of using SBT bud extract as a valid weapon against Influenza and, in addition, as the starting-point for the discovery of new drugs

Peripheral blood biomarkers in multiple sclerosis.

Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. The heteroge-neity of pathophysiological processes in MS contributes to the highly variable course of the disease and unpre-dictable response to therapies. The major focus of the research on MS is the identification of biomarkers inbiologicalfluids, such as cerebrospinalfluid or blood, to guide patient management reliably. Because of the diffi-culties in obtaining spinalfluid samples and the necessity for lumbar puncture to make a diagnosis has reduced,the research of blood-based biomarkers may provide increasingly important tools for clinical practice. However,currently there are no clearly established MS blood-based biomarkers. The availability of reliable biomarkerscould radically alter the management of MS at critical phases of the disease spectrum, allowing for interventionstrategies that may prevent evolution to long-term neurological disability. This article provides an overview ofthis researchfield and focuses on recent advances in blood-based biomarker researc

Epidemiology of intracerebral haemorrhage in Livorno district

BACKGROUND: Intracranial haemorrhage represents the most feared stroke subtype. AIM: To evaluate the burden of intracranial haemorrhage in Tuscany hospitals with special reference to Livorno district. MATERIALS AND METHODS: Data of patients discharged in 2009 from Tuscan and Livorno hospitals with codes ICD-9-CM related to any type of spontaneous intracranial haemorrhage were selected and analyzed. RESULTS: 3,472 patients were discharged from Tuscan hospitals with these diagnoses. Overall mortality was 24.3%. 50% of patients were admitted in Internal Medicine wards. Incidence of intracranial haemorrhage and intracerebral haemorrhage (ICH) in population of Livorno district was 64 and 45/100,000 inhabitants/year with related mortality of 36.5% and 39.4%respectively. Intra-hospital mortality of patients admitted in Livorno hospitals for intracranial haemorrhage were 36.7%. 40% of deaths occurred in the first 48 hours. 69.6% of intracranial haemorrhage were ICHs, 16.8% subaracnoideal. Intra-hospital mortality, admissions for intracranial haemorrhage in respect of total admissions and mortality for intracranial haemorrhage in respect to total mortality increased in the last decade. 23% of patients with intracranial haemorrhage and 16% of patients with ICH underwent to surgical procedures. ICHs related to antithrombotic treatment significantly increased in the last years. Mortality in patients on antithrombotic drugs was three times over compared to that in patients not undergone these drugs (43.7% vs 12.8%, p < 0.01). CONCLUSION: There is an increasing trend in frequency, mortality and hospital burden of intracranial haemorrhage and ICH. Efforts aimed at reducing the burden and consequences of this devasting disease are warranted