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In the era of personalised medicine new biomarkers are required to early diagnose Sjögren's syndrome (SS), to define different disease subsets and to direct patients' clinical management and therapeutic intervention. In the last few years, several efforts have evaluated saliva proteome to detect and monitor primary SS. Although clinically valuable, these studies presented some limitations that have partially prevented the use of salivary biomarkers in clinical practice. Nowadays, proteomic of extracellular vesicle (EV) represents an emerging and promising field in the discovery of -omic biomarkers for pSS. EV is a relatively new term that includes exosomes, microvesicles and apoptotic body. EVs are packed with proteins, growth factors, cytokines, bioactive lipids, but also nucleic acids and in particular: mRNA, microRNA, long non-coding RNA, tRNA and rRNA. Therefore, they may represent a useful source for diagnostic, prognostic and therapeutic biomarkers in several conditions. In this review we will specifically focus on EV proteomics as a tool for the identification of novel biomarkers for pSS. In the first part we focused on the state of the art of the studies on proteomics in SS existing in the literature. In the second part we provided a definition of EV with an update on biological sample collection and processing for EV proteomic studies. Finally, we summarised the state of the art of EV -omics in SS highlighting the potential advantages of this novel approach compared to the overall traditional concept of analysing the proteome of blood or saliva.

Cardiovascular disease (CVD) remains the leading cause of morbility and mortality worldwide. The identification of common cardiovascular risk factors has led to the development of effective treatments that enabled a significant reduction of the global cardiovascular disease burden. However, a significant proportion of cardiovascular risk remains unexplained by these risk factors leaving many individuals at risk of cardiovascular events despite good control of the risk factors. Recent randomized clinical trials and Mendelian randomization studies have suggested that inflammation explains a significant proportion of the residual cardiovascular risk in subjects with good control of risk factors. An accelerated process of vascular ageing is increasingly recognized as a potential mechanism by which inflammation might increase the risk of CVD. In turn, cellular ageing represents an important source of inflammation within the vascular wall, potentially creating a vicious cycle that might promote progression of atherosclerosis, independently from the individual cardiovascular risk factor burden. In this review, we summarise current evidence suggesting a role for biological ageing in CVD and how inflammation might act as a key mediator of this association. © 2019, Italian Society of Hypertension.

The recent development of biological agents, namely, anti-tumour necrosis factor alpha (TNF-α) agents (infliximab, adalimumab and etanercept), anti- CD20 monoclonal antibody (rituximab) and anti-interleukin 6 receptor (IL-6R) monoclonal antibody (tocilizumab), represents a major breakthrough for the treatment of immune-mediated disorders. Given their structural and functional differences, distinct safety profiles can be expected for each of these agents. Evidence in the literature indicates that patients treated with anti-TNF-α agents and tocilizumab are at increased risk for bacterial infections. However, an increased therapeutic use of these biological agents has disclosed other side-effects, including immediate hypersensitivity reactions, such as anaphylaxis and urticaria. Both under-diagnosis and over-diagnosis of hypersensitivity reactions to biological agents are potential problems. Thus, it is important to identify these reactions and to adopt the right approach to manage them. This article reviews the general aspects of adverse events during biologic treatment, focusing on IgE-mediated hypersensitivity reactions to anti-TNF-α agents, rituximab and tocilizumab, and on the tools for the diagnosis of these life-threatening reactions.

To study both systemic and ocular nerve growth factor (NGF) in inflamed juvenile conjunctival nevus (IJCN), a benign, inflammatory juxtalimbal lesion characterized by many intralesional eosinophils, and to investigate the behavior of eosinophils cocultured on lesional and extralesional fibroblasts obtained from IJCN biopsies, in relation to NGF.Eight patients with IJCN (7-15 years old) and six with noninflamed conjunctival compound nevus (12-30 years old) participated in the study. Conjunctival biopsy specimens were used for routine histology, immunohistochemistry (NGF, trkA, eosinophil cationic protein, and tryptase determination), in situ hybridization (NGF mRNA), and determination of fibroblast growth. Blood of patients with IJCN was used to measure NGF levels (by ELISA) and to isolate eosinophils (magnet activated cell sorter [MACS]). Eosinophils were seeded on lesional and extralesional fibroblasts and their adherence, survival (by trypan blue staining), and functional activity (by eosinophil peroxidase [EPO] assay) were assessed after 4 days.NGF in the blood of patients with IJCN and eosinophils and mast cells in their conjunctivas, were significantly elevated. NGF protein, NGF mRNA, and trkA were found to be increased in IJCN biopsy specimens compared with noninflamed compound nevi. Some NGF and trkA colocalized with eosinophils and mast cells. Lesional fibroblasts produced high amounts of NGF in comparison with extralesional fibroblasts and significantly enhanced eosinophil adherence, without influencing either their viability or activation. Adherence and EPO release were increased, in both lesional and extralesional fibroblasts.The triggering factors that lead to the prominent inflammation in IJCN are unknown. The data in the current study, showing the presence of increased NG-trkA, eosinophils, and mast cells in IJCN and the modulation of eosinophil properties by lesional fibroblasts partly through NGF, suggest a possible association between IJCN and allergic inflammation. Alternatively, this process may represent a direct immune response induced by the nevus itself.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease influenced by both genetic and environmental factors. It has been postulated that a high-risk genetic background, in combination with epigenetic marks and environmental exposures, leads to a cascade of events inducing synovitis and consequent destructive arthritis. The clinical picture of joint involvement in RA is the result of chronic inflammation of the synovium, characterised by interactions of resident cells such as fibroblast-like synoviocytes (FLS) with cells of the innate (e.g. macrophages, dendritic cells, mast cells and NK cells, neutrophils) and adaptive immune system (e.g. B and T lymphocytes). Currently, our understanding of the role of innate and adaptive immunity in the pathogenesis of RA is expanding. The concept of how immune responses contribute to the disease has dramatically evolved over the last 50 years. Shedding some light on the different aspects of RA pathogenesis will help to identify new targets for the development of disease-modifying therapies. Thus, in this review we report new insights in RA pathogenesis, resulting from a literature research date published in the last year.