The hepatitis B vaccine and autoimmune/inflammatory syndrome induced by adjuvants: Relationship with Saccharomyces cerevisiae

n/

IL-18 Serum Level in Adult Onset Still's Disease: A Marker of Disease Activity

Introduction. Immunological factors seem to play a pivotal role in Adult Onset Still's Disease (AOSD). Among all, IL-18 cytokine is overexpressed and drives the inflammatory process. Objective. We aimed to investigate the levels of IL-18 in sera of Italian patients with AOSD and to assess its possible role as a marker of disease activity. Methods. IL-18 serum levels were determined by ELISA in 26 Italian patients with AOSD. Disease activity was assessed using Pouchot's criteria. As controls, 21 patients with Rheumatoid Arthritis (RA), 21 patients with Sjogren's Syndrome (SS), 20 patients with Systemic Lupus Erythematosus (SLE), and 21 healthy subjects (normal human sera, NHS) were evaluated. Results. IL-18 serum levels were significantly higher in patients with active AOSD than in non-active (P = 0.001) and control groups (RA P = 0.0070, SS P = 0.0029, SLE P = 0.0032, NHS P = 0.0004). A significant correlation between IL-18 serum levels and disease activity (P < 0.0001), and laboratory parameters as ferritin (P = 0.0127) and C-reactive protein (P = 0.0032) was demonstrated. Conclusions. Higher levels of IL-18 are detected in active AODS patients and correlate with disease activity and inflammatory laboratory features. ROC-AUC analysis of the serum concentration of IL-18 suggests that it can be considered a diagnostic marker of AOSD. This paper supports the targeting of this cytokine as a possible therapeutic option in AOSD

Relationship between gender differences and clinical outcome in patients with the antiphospholipid syndrome

Antiphospholipid syndrome (APS), characterized by artherial and/or venous thrombosis, pregnancy morbidity and "antiphospholipid" antibodies (aPLs), is more common in women than in men, with a female to male ratio of about 3.5:1. Only few studies have investigated the clinical differences between male and female patients with APS. Therefore, this study was aimed to analyze the differences of clinical manifestations and laboratory tests, at diagnosis, between female and male APS patients and the clinical outcome. We enrolled 191 consecutive APS patients (125 with primary APS, PAPS, and 66 with secondary APS, SAPS) with a female predominant ratio of approximately 3:1 (142 vs 49). The prevalence of PAPS was higher in males than females (p&lt;0.001). The analysis of aPL profile revealed that high IgM anti-cardiolipin (aCL) and high-medium IgG aCL titers were more frequent in males. In thrombotic APS peripheral arterial thrombosis was more common in male than female patients (p=0.049), as well as myocardial infarction (p=0.031). Multivariate analysis to correct for cardiovascular risk factors, high titer of aPLs and triple positivity for aPLs, revealed that the odds ratio for myocardial infarction in male was 3.77. Thus, APS may be considered as a disease in which serological (IgM titer) and clinical profiles are influenced by gender

Involvement of substance P (SP) and its related NK1 receptor in primary Sjögren’s syndrome (pSS) pathogenesis

Primary Sjogren's Syndrome (pSS) is a systemic autoimmune disease that primarily attacks the lacrimal and salivary glands, resulting in impaired secretory function characterized by xerostomia and xerophthalmia. Patients with pSS have been shown to have impaired salivary gland innervation and altered circulating levels of neuropeptides thought to be a cause of decreased salivation, including substance P (SP). Using Western blot analysis and immunofluorescence studies, we examined the expression levels of SP and its preferred G protein-coupled TK Receptor 1 (NK1R) and apoptosis markers in biopsies of the minor salivary gland (MSG) from pSS patients compared with patients with idiopathic sicca syndrome. We confirmed a quantitative decrease in the amount of SP in the MSG of pSS patients and demonstrated a significant increase in NK1R levels compared with sicca subjects, indicating the involvement of SP fibers and NK1R in the impaired salivary secretion observed in pSS patients. Moreover, the increase in apoptosis (PARP-1 cleavage) in pSS patients was shown to be related to JNK phosphorylation. Since there is no satisfactory therapy for the treatment of secretory hypofunction in pSS patients, the SP pathway may be a new potential diagnostic tool or therapeutic target

Autophagy hijacking in PBMC From COVID-19 patients results in lymphopenia

Autophagy is a homeostatic process responsible for the self-digestion of intracellular components and antimicrobial defense by inducing the degradation of pathogens into autophagolysosomes. Recent findings suggest an involvement of this process in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the role of autophagy in the immunological mechanisms of coronavirus disease 2019 (COVID-19) pathogenesis remains largely unexplored. This study reveals the presence of autophagy defects in peripheral immune cells from COVID-19 patients. The impairment of the autophagy process resulted in a higher percentage of lymphocytes undergoing apoptosis in COVID-19 patients. Moreover, the inverse correlation between autophagy markers levels and peripheral lymphocyte counts in COVID-19 patients confirms how a defect in autophagy might contribute to lymphopenia, causing a reduction in the activation of viral defense. These results provided intriguing data that could help in understanding the cellular underlying mechanisms in COVID-19 infection, especially in severe forms

Sjögren's syndrome from pathogenesis to novel therapeutic targets

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease, characterised by a chronic infiltration of exocrine glands, mainly salivary glands, with the histological features of focal lymphocytic sialoadenitis. Disease spectrum is broad and the occurrence of several extra-glandular manifestations, and in rare cases lymphoma development, is well known. A specific approved treatment for pSS is still lacking and the detection of novel therapeutic biologic target is ongoing. The identification of biological fingerprints seems essential in order to stratify patients both in clinical trials and in real life. Discovery of new components of the inflammatory response will be the key in the future for the identification of novel additional therapeutic options

Sjögren's syndrome: from pathogenesis to novel therapeutic targets

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease, characterised by a chronic infiltration of exocrine glands, mainly salivary glands, with the histological features of focal lymphocytic sialoadenitis. Disease spectrum is broad and the occurrence of several extra-glandular manifestations, and in rare cases lymphoma development, is well known. A specific approved treatment for pSS is still lacking and the detection of novel therapeutic biologic target is ongoing. The identification of biological fingerprints seems essential in order to stratify patients both in clinical trials and in real life. Discovery of new components of the inflammatory response will be the key in the future for the identification of novel additional therapeutic options

Inflammatory myopathies and overlap syndromes: Update on histological and serological profile

The term 'inflammatory myopathies' (IMs) comprise a group of muscle diseases formed by four main categories known as polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM) and immune-mediated necrotizing myopathy (IMNM). Due to the increasing evidence of IMs over the course of different autoimmune diseases, the overlap myositis (OM) has been recently recognized as a possible stand-alone entity. IMs are characterized by a wide spectrum of autoantibodies, and the panel of myositis-associated autoantibodies (MAA) has dramatically increased over the last years giving the clinicians a further crucial support to differentiate the different types of myositis. This study aims to collect the most relevant evidence published up to date on the most commonly described OM with a particular emphasis on their histological aspects and also serological features

Presentation and diagnosis of adult-onset Still's disease: the implications of current and emerging markers in overcoming the diagnostic challenge

Adult-onset Still's disease (AOSD) is a known cause of fever of unknown origin. It is characterized by a triad of symptoms: spiking fever (>39°C), salmon-colored rash and arthritis/arthralgia. On a predisposing genetic background, several conditions may act as trigger for disease and among these, infectious agents are the most important. Nowadays, a dichotomous view of AOSD has been introduced which distinguishes this entity in two subsets according to the clinical features and laboratory aspects: systemic or articular. As AOSD is a diagnosis of exclusion, specific biomarkers able to facilitate differential diagnosis are needed. A number of possible biomarkers have been proposed that will be discussed in detail in this review: ferritin, IL-18, procalcitonin, s100 proteins and sCD163