Anti-GAPDH Autoantibodies as a Pathogenic Determinant and Potential Biomarker of Neuropsychiatric Diseases.

Objective: To investigate the potential role of circulating autoantibodies specific to neuronal cell surface antigens in the pathophysiology of neuropsychiatric disorders.

Methods: Two different kinds of immunoscreening approaches were used to identify autoantigens associated with neuropsychiatric disorders in the serum of patients with schizophrenia. The presence of autoantibodies specific to the identified autoantigens was then tested in patients with various psychiatric disorders and in patients with systemic lupus erythematosus (SLE) and concomitant neuropsychiatric manifestations.

Integrating gender medicine into the workplace health and safety policy in the scientific research institutions: a mandatory task.

Background: Gender medicine is a multi-faceted field of investigation integrating various aspects of psycho-social and biological sciences but it mainly deals with the impact of the gender on human physiology, pathophysiology, and clinical features of diseases. In Italy, the Decree Law 81/2008 recently introduced the gender issue in the risk assessment at the workplaces.

Aims: This review briefly describes our current knowledge on gender medicine and on the Italian legislation in risk management.

Autoantibodies specific to a peptide of β2-glycoprotein I cross-react with TLR4, inducing a proinflammatory phenotype in endothelial cells and monocytes.

β(2)-glycoprotein I (β(2)GPI) is the major antigenic target for antiphospholipid Abs. Anti-β(2)GPI Abs are a heterogeneous population of Igs targeting all domains of the molecule. Abs specific to β(2)GPI domain I are strongly associated with thrombosis and obstetric complications.

Cystic echinococcosis: aspects of immune response, immunopathogenesis and immune evasion from the human host.

Cystic echinococcosis (CE) is a neglected infectious disease caused by the larval stage of Echinococcus granulosus. It constitutes a major public health problem in developing countries. During CE, the distinguishing feature of the host-parasite relationship is that chronic infection coexists with detectable humoral and cellular responses against the parasite.

Host-parasite relationship in cystic echinococcosis: an evolving story.

The larval stage of Echinococcus granulosus causes cystic echinococcosis, a neglected infectious disease that constitutes a major public health problem in developing countries. Despite being under constant barrage by the immune system, E. granulosus modulates antiparasite immune responses and persists in the human hosts with detectable humoral and cellular responses against the parasite.

Human cystic echinococcosis: old problems and new perspectives.

Cystic echinococcosis (CE) is a widespread chronic endemic helminthic disease caused by infection with metacestodes of the tapeworm Echinococcus granulosus. CE affects humans and has a worldwide prevalence of approximately six million. In this review, we discuss current findings in diagnosis and clinical management of CE and new concepts relating to E.

Identification of a novel 19 kDa Echinococcus granulosus antigen.

By screening an Echinococcus granulosus cDNA library with IgG4 from patients with active cystic echinococcosis (CE), we identified a cDNA encoding a protein of 19.0 kDa (Eg19). Eg19, in 12% SDS-PAGE in reducing and non-reducing conditions, showed several bands between 19 and 100 kDa.

Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus.

In the course of Systemic Lupus Erythematosus (SLE), a variety of neuropsychiatric disturbances is reported with a prevalence ranging from 17% to 75%. The diagnosis of these syndromes is difficult and requires a careful psychiatric evaluation. Distinct autoantibodies detectable in serum or cerebrospinal fluid of patients with SLE are associated with the presence of neuropsychiatric disorders.

Molecular cross-talk in host-parasite relationships: the intriguing immunomodulatory role of Echinococcus antigen B in cystic echinococcosis.

Cystic echinococcosis (CE), a zoonosis caused by the development of Echinococcus granulosus tapeworm larvae in the internal organs of ungulates and humans, continues to pose a major public health burden in underdeveloped and industrialised areas worldwide. Research designed to improve parasitic disease control and find out more about parasite biology has already identified a number of E. granulosus antigenic molecules.

Immunomodulatory mechanisms during Echinococcus granulosus infection.

The pathologic events that ensue after humans ingest the eggs of Echinococcus granulosus and continue while cystic echinococcosis develops, provide an excellent example illustrating the evasive strategies helminth parasites use to develop, progress and cause chronic disease. The hydatid cyst secretes and exposes numerous immunomodulatory molecules to the host's immune system. By characterizing these molecules we can understand the mechanisms that E.

Thioredoxin peroxidase from Echinococcus granulosus: a candidate to extend the antigenic panel for the immunodiagnosis of human cystic echinococcosis.

The currently available tests for the diagnosis of cystic echinococcosis (CE), enzyme-linked immunosorbent assay (ELISA), and immunoblotting (IB) lack sensitivity and specificity, and antigen panels need standardizing. By screening an Echinococcus granulosus cDNA library with IgG1 from patients with CE, we identified E. granulosus thioredoxin peroxidase (EgTPx).

Autoantibodies to the C-terminal subunit of RLIP76 induce oxidative stress and endothelial cell apoptosis in immune-mediated vascular diseases and atherosclerosis.

Although detection of autoantibodies in the peripheral blood from patients with immune-mediated endothelial dysfunctions has so far failed to provide tools of diagnostic or pathogenetic value, putative bioindicators include anti-endothelial cell antibodies, a heterogeneous family of antibodies that react with autoantigens expressed by endothelial cells. In this study, to identify endothelial autoantigens involved in the autoimmune processes causing endothelial damage, we screened a human microvascular endothelial cell cDNA library with sera from patients with Behçet's disease. We identified antibodies to the C-terminus of Ral binding protein1 (RLIP76), a protein that catalyzes the ATP-dependent transport of glutathione (GSH) conjugates including GSH-4-hydroxy-t-2,3-nonenal, in the serum of a significant percentage of patients with various diseases characterized by immune-mediated endothelial dysfunction, including Behçet disease, systemic sclerosis, systemic lupus erythematosus and carotid atherosclerosis.

Screening of a microvascular endothelial cDNA library identifies rabaptin 5 as a novel autoantigen in Alzheimer's disease.

The pathogenesis of Alzheimer's disease (AD) includes the participation of the immune system. To identify antigenic targets in AD, we screened a human microvascular endothelial cell cDNA library with sera from patients with AD, and we identified rabaptin 5 (RABPT5). We detected serum IgG specific to RABPT5 in 65% of patients with AD and in 35% of patients with systemic lupus erythematosus, but in no healthy controls.

Free hemoglobin: a dangerous signal for the immune system in patients with carotid atherosclerosis?

Atherosclerosis is a chronic inflammatory multifactorial disease in which immune responses are key pathogenetic factors. T cell-mediated immunity contributes to the initiation and progression of atherosclerotic disease, but the nature of antigens responsible for immune cell activation is still not completely elucidated. Convincing evidence supports a determinant role of autoimmune responses to self-structures in shaping the progression of the disease.

Screening of endothelial expression libraries for the identification of novel autoantigens involved in distinct autoimmune diseases characterized by endothelial dysfunction.

Screening a cDNA expression library is a powerful technique that allows identification of previously uncharacterized antigens. Proteins recognized by antibodies from patients with autoimmune diseases have been intensively studied over the past two decades since cDNAs encoding autoantigens have become available. Identity of many of them has been defined, and specific structural motifs or post-translational modifications, which may be important to explain the generation of such antibodies during the autoimmune process, have been pointed out.

Echinococcus granulosus antigen B impairs human dendritic cell differentiation and polarizes immature dendritic cell maturation towards a Th2 cell response.

Despite inducing a strong host cellular and humoral immune response, the helminth Echinococcus granulosus is a highly successful parasite that develops, progresses, and ultimately causes chronic disease. Although surgery remains the preferred therapeutic option, pharmacological research now envisages antihelminthic strategies. To understand the mechanisms that E.

Intracellular expression of cytokines in peripheral blood from patients with atherosclerosis before and after carotid endarterectomy.

Objective: We investigated the possible association of intracellular cytokine profiles in peripheral mononuclear cells in whole blood from patients with carotid atherosclerosis in whom follow-up after carotid endarterectomy (CEA) showed the onset or progression of contralateral disease.

Methods And Results: Intracellular expression of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6, IL-8, IL-4 and IL-10 was determined in 43 patients with carotid atherosclerosis, at baseline and at 1, 3, 6 and 12 months after CEA, and in 16 healthy subjects. When follow-up ended patients were divided into two groups, those with cured or stable disease (no onset of disease or unchanged stenosis in the contralateral vessel) and those with progressive disease (onset of disease or increased stenosis in the contralateral vessel).

Identification and characterization of the carboxy-terminal region of Sip-1, a novel autoantigen in Behçet's disease.

Given the lack of a serological test specific for Behçet's disease, its diagnosis rests upon clinical criteria. The clinical diagnosis is nevertheless difficult because the disease manifestations vary widely, especially at the onset of disease. The aim of this study was to identify molecules specifically recognized by serum autoantibodies in patients with Behçet's disease and to evaluate their diagnostic value.

Oxidized beta2-glycoprotein I induces human dendritic cell maturation and promotes a T helper type 1 response.

The human plasma protein beta2-glycoprotein I (beta2-GPI) is the most common target for antiphospholipid antibodies associated with thrombotic events in chronic disorders related to endothelial cell dysfunction. Crucial information is needed to clarify why this self-abundant protein is targeted by autoimmune responses. In this study, we investigated whether oxidative modification of beta2-GPI, either spontaneous in culture wells or induced by treatment with H2O2, renders this self-protein able to activate immature monocyte-derived dendritic cells (DCs) from healthy human donors.

Screening of an endothelial cDNA library identifies the C-terminal region of Nedd5 as a novel autoantigen in systemic lupus erythematosus with psychiatric manifestations.

Anti-endothelial-cell antibodies are associated with psychiatric manifestations in systemic lupus erythematosus (SLE). Our primary aim in this study was to seek and characterize molecules that behave as endothelial autoantigens in SLE patients with psychiatric manifestations. By screening a cDNA library from human umbilical artery endothelial cells with serum from an SLE patient with psychosis, we identified one positive strongly reactive clone encoding the C-terminal region (C-ter) of Nedd5, an intracytoplasmatic protein of the septin family.

An update on immunodiagnosis of cystic echinococcosis.

Immunological parameters are increasingly investigated as possible markers for the development of cystic echinococcosis. Among the newer immunologic tests for assessing the host-parasite relationship, assay of immunoglobulin isotypes with the use of distinct parasite antigens and detection of Th1/Th2 cytokine expression are an interesting new approach. The findings upon which we have constructed our immunological hypothesis of the host-parasite relationship are: (1) immunoglobulin isotype profiles differ in patients with distinct clinical outcomes of the disease; in particular, antigen B is the antigen of choice to detect specific IgG4, which is the immunoglobulin isotype most clearly associated with the progression of the disease; (2) the isolation and characterisation of recombinant parasite proteins that behave as molecular markers of allergic reactions associated with cystic echinococcosis; (3) Th1/Th2 cell activation is involved in the clinical outcome of Echinococcus granulosus infection and, in particular Th2 response, is associated with susceptibility to the disease, whereas a Th1 response is associated with protective immunity.