Dimitri Peterlana

In chronic idiopathic urticaria autoantibodies against FcεRII/CD23 induce histamine release via eosinophil activation

Background Chronic idiopathic urticaria is a common skin disorder characterized by recurrent, transitory, itchy weals for more than 6 weeks. An autoimmune origin has been suggested based on the findings of auto‐antibodies (Abs) directed against either the α subunit of the high‐affinity IgE receptor or the IgE molecule in nearly half of the patients.

Endothelial Cells' Activation and Apoptosis Induced by a Subset of Antibodies against Human Cytomegalovirus: Relevance to the Pathogenesis of Atherosclerosis

Background Human cytomegalovirus (hCMV) is involved in the pathogenesis of atherosclerosis. We have previously shown in patients with atherosclerosis that antibodies directed against the hCMV-derived proteins US28 and UL122 are able to induce endothelial cell damage and apoptosis of non-stressed endothelial cells through cross-rection with normally expressed surface molecules. Our aim was to dissect the molecular basis of such interaction and to investigate mechanisms linking innate immunity to atherosclerosis. Methodology/Principal Findings We analysed the gene expression profiles in endothelial cells stimulated with antibodies affinity-purified against either the UL122 or the US28 peptides using the microarray technology. Microarray results were validated by quantitative PCR and by detection of proteins in the medium. Supernatant of endothelial cells incubated with antibodies was analysed also for the presence of Heat Shock Protein (HSP)60 and was used to assess stimulation of Toll-Like Receptor-4 (TLR4). Antibodies against UL122 and US28 induced the expression of genes encoding for adhesion molecules, chemokines, growth factors and molecules involved in the apoptotis process together with other genes known to be involved in the initiation and progression of the atherosclerotic process. HSP60 was released in the medium of cells incubated with anti-US28 antibodies and was able to engage TLR4. Conclusions/Significance Antibodies directed against hCMV modulate the expression of genes coding for molecules involved in activation and apoptosis of endothelial cells, processes known to play a pivotal role in the pathogenesis of atherosclerosis. Moreover, endothelial cells exposed to such antibodies express HSP60 on the cell surface and release HSP60 in the medium able to activate TLR4. These data confirm that antibodies directed against hCMV-derived proteins US28 and UL122 purified from patients with coronary artery disease induce endothelial cell damage and support the hypothesis that hCMV infection may play a crucial role in mediating the atherosclerotic process.

Endothelin‐1 serum levels correlate with MCP‐1 but not with homocysteine plasma concentration in patients with systemic sclerosis

Objectives: To determine whether homocysteine (Hcy) plasma levels are correlated with molecules indicative of endothelial cell and fibroblast activation, including endothelin‐1 (ET‐1) and monocyte chemoattractant protein‐1 and ‐3 (MCP‐1, MCP‐3), in patients with systemic sclerosis (SSc). Methods: Eighty‐two patients were enrolled in this study; the control group included 75 age‐ and sex‐matched subjects. Plasma Hcy was determined by high‐performance liquid chromatography; folic acid, and vitamin B12 plasma levels were determined by a chemiluminescence method. ET‐1, MCP‐1, and MCP‐3 were determined by enzyme‐linked immunosorbent assay (ELISA). Analysis of the 677C→T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was performed by polymerase chain reaction (PCR) and digestion with the enzyme HinfI. Results: Hcy levels were lower in patients whereas ET‐1 was significantly higher in patients and correlated with MCP‐1. Stratification of the patients on the basis of Hcy levels was not associated with any statistical difference in the concentration of ET‐1, MCP‐1, and MCP‐3. Patients with diffuse disease presented the highest levels of ET‐1 and MCP‐1. The distribution of the MTHFR genotypes was not different in patients and controls. Conclusions: In SSc, Hcy plasma concentration does not influence ET‐1, MCP‐1, or MCP‐3 levels. On the contrary, ET‐1, a marker of vascular activation, correlates with MCP‐1, a chemokine involved in the fibrotic process of SSc.

Schnitzler's syndrome treated successfully with intravenous pulse cyclophosphamide

Schnitzlers syndrome is a rare clinical condition characterized by chronic urticaria, intermittent fever, bone pain, arthralgia or arthritis, and monoclonal immunoglobulin M (IgM) gammopathy. Here we describe the case of a 48‐year‐old Italian female with a long history of arthralgia, leucocytosis, spiking fever, and chronic urticaria with severe pruritus. The IgM‐κ monoclonal component in the serum and bone densification on conventional X‐ray with hyperfixation on bone technetium scanning at the distal part of the femurs and at the proximal part of the tibias were detected 4 years after the onset of the symptoms. After many ineffective treatments, the use of pulse cyclophosphamide (CPX) resulted in complete remission of the disease that is still lasting after a 2‐year follow‐up.

Reactive arthritis following BCG immunotherapy for bladder carcinoma

Intravesical instillation of bacillus Calmette-Guérin (BCG) is used in the treatment of patients with intermediate and high-risk superficial bladder carcinoma with efficacy and safety. The vast majority of patients do not present any side effects and only 5% of patients have mild and short-lived clinical manifestations such as malaise, low-grade fever, cystitis, and hematuria. Arthralgia and/or arthritis is one of the rare severe complications following intravesical BCG immunotherapy. We report here the case of a patient with reactive arthritis successfully treated with nonsteroidal anti-inflammatory drugs (NSAIDs) after the discontinuation of BCG immunotherapy.

Antiflagellin antibodies recognize the autoantigens Toll‐Like Receptor 5 and Pals 1‐associated tight junction protein and induce monocytes activation and increased intestinal permeability in Crohn’s disease

Background and objectives.  Bacterial flagellin is considered an important antigen in Crohn’s disease (CD) as it activates innate immunity through Toll‐Like Receptor 5 (TLR5) engagement and induces an elevated adaptive immune response. Little is known about the presence of an autoimmune process in CD. We aimed to identify pathogenically relevant autoantigen targets in CD.

Dermatomyositis complicated with Kaposi sarcoma: A case report

We describe the case of a 75-year-old Italian woman affected by dermatomyositis (DM) treated with steroid, high-dose intravenous immunoglobulins (IVIgs) and cyclophosphamide (CPX), taken orally. After a few months, the patient presented multiple red vascular skin lesions diagnosed as Kaposi sarcoma (KS). Steroid was furtherly reduced, and CPX was stopped. We put the patient on chemotherapy with intravenous infusion of vinblastine and vincristine on alternate weeks obtaining the remission of KS. DM is well controlled by a low-dosage steroid and high-dose IVIgs.