Adrenal insufficiency is a contraindication for omalizumab therapy in mast cell activation disease: risk for serum sickness.

Omalizumab is an effective therapeutic humanized murine IgE antibody in many cases of primary systemic mast cell activation disease (MCAD). The present study should enable the clinician to recognize when treatment of MCAD with omalizumab is contraindicated because of the potential risk of severe serum sickness and to report our successful therapeutic strategy for such adverse event (AE). Our clinical observations, a review of the literature including the event reports in the FDA AE Reporting System, the European Medicines Agency Eudra-Vigilance databases (preferred search terms: omalizumab, Xolair®, and serum sickness) and information from the manufacturer's Novartis database were used.

Consultancy and surveillance of post-immunisation adverse events in the Veneto region of Italy for 1992-2008.

Prevention and control of adverse events following immunization (AEFI) are fundamental activities of successful immunisation programs. AEFI reporting, investigation and analysis, integrated by consultancy for subjects needing a specialized evaluation, represent an ideal model for vaccine safety surveillance. In the Veneto Region of Italy the Green Channel Centre has been created by the local Public Health authority, to offer a consultancy activity for vaccinations at risk of adverse events and to ensure an efficient AEFI surveillance system with regular feedback data for vaccine personnel.

A comparative method for processing immunological parameters: developing an "Immunogram".

Background: The immune system is a network of numerous cells that communicate both directly and indirectly with each other. The system is very sensitive to antigenic stimuli, which are memorised, and is closely connected with the endocrine and nervous systems. Therefore, in order to study the immune system correctly, it must be considered in all its complexity by analysing its components with multiparametric tools that take its dynamic characteristic into account.

IFN-gamma-mediated upmodulation of MHC class I expression activates tumor-specific immune response in a mouse model of prostate cancer.

De novo expression of B7-1 impaired tumorigenicity of TRAMP-C2 mouse prostate adenocarcinoma (TRAMP-C2/B7), but it did not elicit a protective response against TRAMP-C2 parental tumor, unless after in vitro treatment with IFN-gamma. TRAMP-C2 cells secrete TGF-beta and show low MHC-I expression. Treatment with IFN-gamma increased MHC-I expression by induction of some APM components and antagonizing the immunosuppressant activity of TGF-beta.

The puzzling uniqueness of the heterotrimeric G15 protein and its potential beyond hematopoiesis.

Heterotrimeric G proteins transduce the signals of the largest family of membrane receptors (G protein-coupled receptors, GPCRs) hence triggering the activation of a wide variety of physiological responses. G15 is a G protein characterized by a number of functional peculiarities that make its signaling exceptional: 1) it can couple a variety of Gs-, Gi/o-, and Gq-linked receptors to phospholipase C activation; 2) relatively to other G proteins, it is poorly affected by beta-arrestin-dependent desensitization, the general mechanism that regulates GPCR function and 3) at the protein level, its expression is only detected in highly specific cell types (hematopoietic and epithelial cells). G15 alpha-subunit displays unique structural and biochemical properties, and is phylogenetically the most recent and divergent component of the Galphaq/11 subfamily.

Expression of CD27 and CD23 on peripheral blood B lymphocytes in humans of different ages.

Background: Due to the fact that the coexpression of CD23 and CD27 has been reported to occur in B lymphocytic leukaemic clones and that there is debate about CD23 expression on memory B cells, we evaluated the behaviour of naive B cells (CD23-/CD27-) and memory B cells (CD27+) in the peripheral blood of a large number of humans of all ages. B cells were also distinguished into B2 (CD5-) and B1-a cells (CD5+).

Methods: The cell surface expression of CD19, CD5, CD23 and CD27 was assessed on peripheral blood lymphocytes from 1,427 subjects of all ages undergoing peripheral blood immunophenotyping for a variety of reasons.

Heterotrimeric G proteins demonstrate differential sensitivity to beta-arrestin dependent desensitization.

G15 is a heterotrimeric G protein of the Gq/11 family. In this study, we describe its exceptional poor sensitivity to the general regulatory mechanism of G protein-coupled receptor (GPCR) desensitization. Enhancing beta2 adrenergic receptor desensitization by arrestin overexpression, did not affect signalling to G15.

The prostate specific membrane antigen regulates the expression of IL-6 and CCL5 in prostate tumour cells by activating the MAPK pathways.

The interleukin-6 (IL-6) and the chemokine CCL5 are implicated in the development and progression of several forms of tumours including that of the prostate. The expression of the prostate specific membrane antigen (PSMA) is augmented in high-grade and metastatic tumors. Observations of the clinical behaviour of prostate tumors suggest that the increased secretion of IL-6 and CCL5 and the higher expression of PSMA may be correlated.

Vaccine adverse event monitoring systems across the European Union countries: time for unifying efforts.

A survey conducted among 26 European Countries within the Vaccine European New Integrated Collaboration Effort (VENICE) project assessed the status of organization in prevention and management of adverse events following immunization (AEFI) and level of interconnection, with the aim at individuating points of strength and weakness. The emerging picture is for a strong political commitment to control AEFIs in Member States (MS), but with consistent heterogeneity in procedures, regulations and capacity of systems to collect, analyze and use data, although with great potentialities. Suggestions are posed by authors to promote actions for unifying strategies and policies among MS.

National seasonal influenza vaccination survey in Europe, 2008.

A cross-sectional survey was undertaken with the European Union (EU) Member States and Norway and Iceland to describe seasonal influenza immunisation in the 2006-7 season, in particular to identify country-specific recommendations for risk groups, obtain vaccine uptake information and allow comparison with global recommendations. A standardised questionnaire was completed electronically by each country's project gatekeeper. Of the 29 countries surveyed, 28 recommended seasonal influenza vaccination for older age groups (22 for those aged > 65 years), and in one country vaccine was recommended for all age groups.

Differential response of human basophil activation markers: a multi-parameter flow cytometry approach.

Background: Basophils are circulating cells involved in hypersensitivity reactions and allergy but many aspects of their activation, including the sensitivity to external triggering factors and the molecular aspects of cell responses, are still to be focused. In this context, polychromatic flow cytometry (PFC) is a proper tool to investigate basophil function, as it allows to distinguish the expression of several membrane markers upon activation in multiple experimental conditions.

Methods: Cell suspensions were prepared from leukocyte buffy coat of K2-EDTA anticoagulated blood specimens; about 1500-2500 cellular events for each tested sample, gated in the lymphocyte CD45dim area and then electronically purified as HLADRnon expressing/CD123bright, were identified as basophilic cells.

Viable Newcastle disease vaccine strains in a pharmaceutical dump.

To assess the viability of discarded and buried vaccine strains, we examined vaccines that had been buried for >20 years in an industrial waste dump in the city of Milan, Italy. Viability results showed potential biological risk associated with uncontrolled burial of pharmaceutical industry waste, including some live vaccines.

Immune regulation by mesenchymal stem cells derived from adult spleen and thymus.

We show here that human and mouse mesenchymal stem cells (MSCs) can be obtained not only from bone marrow (BM), but also from adult spleen and thymus. In vitro, both human and mouse spleen- and thymus-derived MSCs exhibit immunophenotypic characteristics and differentiation potential completely comparable to BM-MSCs. In addition, they can inhibit immune responses mediated by activated T lymphocytes with efficiency comparable to BM-MSCs.

Specific alloantigen self-control by regulatory T cells in organ transplantation: a review.

Multidrug immunosuppressive protocols have increased short-term patient and graft survival rates from 50% to 90% in the past two decades. Unfortunately, chronic graft rejection still remains the main cause of long-term failure and patients must undergo lifelong immunosuppression. The severe side effects such as life-threatening infections, secondary malignancies, and cardiovascular dysfunction all together include roughly 50% of deaths among kidney transplant patients with functioning grafts.

Changes of human B and B-1a peripheral blood lymphocytes with age.

In 2057 consecutive subjects admitted to the Department of Pathology, Section of Immunology of the Verona University Hospital, CD19+ and CD5/CD19 double positive cells were determined to assess the behaviour of total peripheral B-lymphocytes and B-1a (CD5+) compartments in humans during aging. We show that the absolute number of total B lymphocytes increases about three-fold from the baseline conditions in the first year of life and progressively decreases until adult age. A slower decrease was detected from the adult age onwards.

Novel prion protein conformation and glycotype in Creutzfeldt-Jakob disease.

Objective: To describe a novel molecular and pathological phenotype of Creutzfeldt-Jakob disease. Patient A 69-year-old woman with behavioral and personality changes followed by rapidly evolving dementia.

Results: Postmortem examination of the brain showed intracellular prion protein deposition and axonal swellings filled with amyloid fibrils.

In celiac disease, a subset of autoantibodies against transglutaminase binds toll-like receptor 4 and induces activation of monocytes.

Background: Celiac disease is a small intestine inflammatory disorder with multiple organ involvement, sustained by an inappropriate immune response to dietary gluten. Anti-transglutaminase antibodies are a typical serological marker in patients with active disease, and may disappear during a gluten-free diet treatment. Involvement of infectious agents and innate immunity has been suggested but never proven.

Monitoring of cellular immunity by interferon-gamma enzyme-linked immunosorbent spot assay in kidney allograft recipients: preliminary results of a longitudinal study.

Several efforts have been made in past years to identify markers for patients at heightened risk of acute and chronic immune-mediated allograft rejection. The ex vivo monitoring of cellular immunity by the enzyme-linked immunosorbent spot (ELISPOT) assay has recently emerged as a primary tool in predicting short- and long-term outcomes in kidney allograft recipients. Therefore, we started the systematic application of interferon-gamma (IFN-gamma) ELISPOT assay to measure the frequency of producing IFN-gamma in recipient peripheral blood lymphocytes (PBLs) stimulated with donor lymphocytes before and 7, 14, 21, 28, and 60 days after transplantation.

Induction of human immunodeficiency virus neutralizing antibodies using fusion complexes.

Human immunodeficiency virus-1 (HIV-1) infects cells by membrane fusion that is mediated by the envelope proteins gp120/gp41 and the cellular receptors CD4 and CCR5. During this process, some conserved viral epitopes are temporarily exposed and may induce a neutralizing antibody response when fixed in the fusogenic conformation. These transient structures are conserved and may be effective antigens for use in an anti-HIV-1 vaccine.

Constitutive activation of p38 and ERK1/2 MAPKs in epithelial cells of myasthenic thymus leads to IL-6 and RANTES overexpression: effects on survival and migration of peripheral T and B cells.

Myasthenia gravis (MG) is an autoimmune disease of neuromuscular junctions where thymus plays a pathogenetic role. Thymectomy benefits patients, and thymic hyperplasia, a lymphoid infiltration of perivascular spaces becoming site of autoantibody production, is recurrently observed. Cytokines and chemokines, produced by thymic epithelium and supporting survival and migration of T and B cells, are likely to be of great relevance in pathogenesis of thymic hyperplasia.