Sjögren's syndrome: a systemic autoimmune disease.

Sjögren's syndrome is a chronic autoimmune disease characterized by ocular and oral dryness resulting from lacrimal and salivary gland dysfunction. Besides, a variety of systemic manifestations may occur, involving virtually any organ system. As a result, the disease is characterized by pleomorphic clinical manifestations whose characteristics and severity may vary greatly from one patient to another.

Iloprost use and medical management of systemic sclerosis-related vasculopathy in Italian tertiary referral centers: results from the PROSIT study.

Vasculopathy is a crucial feature of systemic sclerosis (SSc), and Raynaud's phenomenon (RP) and digital ulcers (DU) have a deep impact on the quality of patients' life. The management of vascular disease can be challenging for the clinician because of the suboptimal tolerability of the treatments and lack of consensus on the best therapeutic approach. Intravenous iloprost, a synthetic analogue of prostacyclin, is broadly used for the treatment of RP and ischemic ulcers secondary to SSc.

Rationale for an Association Between PD1 Checkpoint Inhibition and Therapeutic Vaccination Against HIV.

The pathogenesis of HIV immunodeficiency is mainly dependent on the cytopatic effects exerted by the virus against infected CD4+ T cells. However, CD4+ T cell loss cannot be the only pathogenic factor since severe opportunistic infections may develop in HIV infected patients with normal CD4+ T cell counts and since the recent START study indicated that absolute CD4+ T cell counts are not predictive for AIDS and non-AIDS events. Recently our group demonstrated that CD8+CD28-CD127lowCD39+ regulatory T lymphocytes, previously found highly concentrated within tumor microenvironment, circulate with elevated frequency in the peripheral blood of HIV infected patients.

Beyond APECED: An update on the role of the autoimmune regulator gene (AIRE) in physiology and disease.

The autoimmune regulator gene (AIRE) is a transcription factor expressed both in the thymus, by medullary thymic epithelial cells, and in secondary lymphoid organs. AIRE controls the local transcription of organ- specific proteins typically expressed in peripheral tissues, thus allowing the negative selection of self- reactive T cells. The crucial role played by AIRE in central immune tolerance emerged in the studies on the pathogenesis of Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy, a rare inherited polyendocrine/autoimmune disease.

AIRE polymorphism, melanoma antigen-specific T cell immunity, and susceptibility to melanoma.

AIRE is involved in susceptibility to melanoma perhaps regulating T cell immunity against melanoma antigens (MA). To address this issue, AIRE and MAGEB2 expressions were measured by real time PCR in medullary thymic epithelial cells (mTECs) from two strains of C57BL/6 mice bearing either T or C allelic variant of the rs1800522 AIRE SNP. Moreover, the extent of apoptosis induced by mTECs in MAGEB2-specific T cells and the susceptibility to in vivo melanoma B16F10 cell challenge were compared in the two mouse strains.

The antiphospholipid syndrome: from pathophysiology to treatment.

Antiphospholipid antibody syndrome (APS) is an autoimmune acquired thrombophilia characterized by recurrent thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). APS can be primary, if it occurs in the absence of any underlying disease, or secondary, if it is associated with another autoimmune disorder, most commonly systemic lupus erythematosus. The exact pathogenetic mechanism of APS is unknown, but different, not mutually exclusive, models have been proposed to explain how anti-PL autoantibodies might lead to thrombosis and pregnancy morbidity.

Vasculitides: Proposal for an integrated nomenclature.

The vasculitides form a heterogeneous group of systemic diseases that differ in etiology, histological patterns, and, consequently, clinical significance and prognosis but are traceable to the same pathological event, namely, vessel wall inflammation. The clinical heterogeneity among these diseases, together with yet unknown pathogenetic mechanisms for many of them, creates difficulties in the early diagnosis and correct management of affected patients. Therefore, several groups of investigators have elaborated nomenclatures to set some order in the definition and grouping of the vasculitides.

Efficacy of cilostazol for the treatment of Raynaud's phenomenon in systemic sclerosis patients.

Cilostazol is a selective inhibitor of phosphodiesterase-III with antiplatelet, antithrombotic and vasodilating properties. The aim of our study was to evaluate the effect of the drug on vasculopathy and Raynaud's phenomenon (RP), in a series of patients with systemic sclerosis (SSc), before and after cilostazol treatment. Twenty-one consecutive SSc patients with moderate or severe RP were enrolled in an open-label study.

Early and repeated IgG1Fc-pCons chimera vaccinations (GX101) improve the outcome in SLE-prone mice.

A previous study showed that a tolerogenic gene vaccine based on a IgG1Fc-pCons chimera (here named GX101) protects NZB/NZW mice from SLE development. The present study was aimed at identifying the most effective schedule of immunization and the possible involvement of CD4(+) Foxp3(+) Treg in the mechanism of action, in view of its eventual translation to the human studies. NZB/NZW mice were vaccinated with B lymphocytes made transgenic by spontaneous transgenesis with a gene coding for a chimeric IgG1Fc-pCons construct.

A multi-peptide, dual-adjuvant telomerase vaccine (GX301) is highly immunogenic in patients with prostate and renal cancer.

Background: Anti-tumor vaccination is a new frontier in cancer treatment applicable to immunogenic neoplasms such as prostate and renal cancers. GX301 is a vaccine constituted by four telomerase peptides and two adjuvants, Montanide ISA-51 and Imiquimod.

Objective: The aim of this study was to analyze safety and tolerability of GX301 in an open-label, phase I/II trial.

Cyclophosphamide inhibits the generation and function of CD8(+) regulatory T cells.

CD8(+) regulatory T cells (Treg) and CD4(+)CD25(+) Treg infiltrate human cancers, thus favoring tumor immune escape. Therefore, in the setting of antitumor therapeutic protocols, it is important to associate antitumor treatment with agents that are able to inhibit Treg function. Cyclophosphamide (CY) has been demonstrated to be effective in counteracting CD4(+)CD25(+) Treg activity.

Role of advanced oxidation protein products and Thiol ratio in patients with acute coronary syndromes.

Objectives: To identify systemically detectable vascular inflammation associated to redox system unbalance, advanced oxidation protein products (AOPP), formed by HClO reaction with proteins, Thiol levels, and their ratio (AOPP/Thiol ratio) were measured in patients with acute coronary syndromes (ACS).

Design And Methods: We evaluated AOPP/Thiol ratio together with CRP and IL-1β in 18 acute myocardial infarction (AMI) and in 16 unstable angina (UA) patients at admission, and in 16 control subjects (CTR); the measurements were repeated at 1 and at 6 months.

Results: At admission, AMI and UA patients displayed higher AOPP/Thiol ratio and CRP and IL-1β compared to CTR subjects.

Alteration of Th17 and Treg cell subpopulations co-exist in patients affected with systemic sclerosis.

Aim of the study has been to understand the relationship between TH17 and Treg cell subsets in patients affected with systemic sclerosis (SSc). Phenotypes and functions of Th17 and Treg cell subsets were analyzed in a series of 36 SSc patients. Th17 cell concentration in the peripheral blood was found to be increased in SSc patients with respect to healthy controls independently from type or stage of disease.

CD8(+) T regulatory/suppressor cells and their relationships with autoreactivity and autoimmunity.

Regulatory T lymphocytes (Treg) are fundamental for immune homeostasis since they contribute to the induction of peripheral tolerance to autologous antigens and regulate effector immune responses. Treg subsets are present within both the CD4+and the CD8(+) T cell compartments. Considering the CD8(+) Treg, in the last decades several subpopulations, provided with different phenotypes and mechanisms of action, have been characterized.

Phenotypical and functional alterations of CD8 regulatory T cells in primary biliary cirrhosis.

The mechanisms that lead to loss of tolerance in autoimmune disease have remained both elusive and diverse, including both genetic predisposition and generic dysregulation of critical mononuclear cell subsets. In primary biliary cirrhosis (PBC), patients exhibit a multilineage response to the E2 component of pyruvate dehydrogenase involving antibody as well as autoreactive CD4 and CD8 responses. Recent data from murine models of PBC have suggested that a critical mechanism of biliary destruction is mediated by liver-infiltrating CD8 cells.

Iodized oil pleural effusion in a patient previously treated with transarterial chemoembolization for hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is a nonsurgical therapeutic option for the control of hepatocellular carcinoma (HCC) in patients with cirrhosis. Although less invasive than surgical approaches, this procedure can have severe side effects, with both local and extrahepatic complications, mostly related to treatment-induced ischemic damage. Here, we describe the case of a cirrhotic female patient affected by multinodular HCC, who presented with sudden onset dyspnea and chest pain.

Brachial artery endothelial-dependent flow-mediated dilation identifies early-stage endothelial dysfunction in systemic sclerosis and correlates with nailfold microvascular impairment.

Objective: To assess possible correlations between endothelial-dependent flow-mediated dilation (FMD) of the brachial artery and nailfold videocapillaroscopy (NVC) in patients with systemic sclerosis (SSc). Evidence has shown that vascular impairment in SSc may be a sign of endothelial dysfunction involving both microvascular and macrovascular systems, although the pathological mechanisms of the dysfunction are poorly understood.

Methods: Forty-three consecutive patients (mean age 51 +/- 11 yrs) with SSc were studied.

[Possible connection between gastroesophageal reflux and interstitial pulmonary fibrosis in patients with systemic sclerosis].

Interstitial lung disease represents the main cause of morbidity and mortality in patients with systemic sclerosis. The mechanisms leading to interstitial lung disease are poorly understood and thus current strategies have little effect on this progressive and fatal disease. Therefore, it appears relevant the importance to assess the possible risk factors involved in its pathogenesis.

sHLA-I contaminating molecules as novel mechanism of ex vivo/in vitro transcriptional and posttranscriptional modulation of transforming growth factor-beta in CD8+ T lymphocytes and neutrophils after intravenous immunoglobulin treatment.

Background: Numerous mechanisms have been proposed to explain the beneficial action of intravenous immune globulin (IVIG) in autoimmune and systemic inflammatory disorders. Among others' data, an in vitro increase of intracellular TGF-beta expression when culturing CD4+ T lymphocytes in the presence of IVIG has been reported. As IVIG infusion involves administration of soluble contaminants likewise all hemoderivative preparations, we hypothesized that, besides several other immunomodulatory proposed mechanisms, the clinical effects of IVIG therapy might be, at least partly, due to contaminating soluble HLA Class I (sHLA-I) molecules capable to exert pleiotropic immunomodulatory effects among which TGF-beta(1) modulation.

Behavior of non-classical soluble HLA class G antigens in human immunodeficiency virus 1-infected patients before and after HAART: comparison with classical soluble HLA-A, -B, -C antigens and potential role in immune-reconstitution.

We have reported that serum level of soluble HLA-A, -B, -C (sHLA-A,-B,-C) antigens is elevated in HIV-infected subjects and decreases after antiretroviral therapy (HAART). In this study, we measured the levels of soluble HLA-G (sHLA-G) antigens in a cohort of HIV-infected patients before and during HAART. sHLA-G and sHLA-A, -B, -C levels were significantly elevated in HIV-infected subjects as compared with controls before antiretroviral treatment and significantly decreased after 36 months of HAART.

Flu vaccination with a virosomal vaccine does not affect clinical course and immunological parameters in scleroderma patients.

Safety and efficacy of adjuvanted vaccines in autoimmune individuals raises growing clinical and scientific interest. Protection from influenza would bring particular benefits in these patients with common cardiac and respiratory impairment. This study evaluates efficacy, clinical safety and immune effects of the administration of a single dose of a virosomal flu vaccine in 46 scleroderma patients.

Gastroesophageal reflux and pulmonary fibrosis in scleroderma: a study using pH-impedance monitoring.

Rationale: Interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) is associated with increased morbidity and mortality. Gastroesophageal reflux (GER) is considered a contributing factor in the pathogenesis of ILD.

Objectives: To characterize GER (acid and nonacid) in patients with SSc with and without ILD.

New therapies in SLE.

The therapy of systemic lupus erythematosus (SLE), a systemic autoimmune disease of unknown aetiology, is significantly complicated by the diversity of disease manifestations and by a variety of complex immune abnormalities. Recent preclinical studies have shown the therapeutic efficacy of several drugs and/or new compounds, some of which have been tested in clinical trials. This review provides an update on the use of new approaches in SLE and recent patents that could develop into novel therapeutics available to the clinical armamentarium for the management of the disease.

Traditional and non traditional risk factors in accelerated atherosclerosis in systemic lupus erythematosus: role of vascular endothelial growth factor (VEGATS Study).

Objective: To evaluate the role of vascular endothelial growth factor (VEGF) in accelerated atherosclerosis in patients with Systemic Lupus Erythematosus (SLE).

Methods: We have enrolled 80 SLE female patients and 80 age-matched healthy control females who underwent a structured interview, physical examination, routine laboratory tests, VEGF plasma level determination and B-mode ultrasonography of carotid arteries to determine carotid intima media thickness (IMT). Framingham risk factors for cardiovascular events were also calculated and VEGF plasma levels were correlated with traditional and nontraditional cardiovascular risk factors.