Increased level of H-ferritin and its imbalance with L-ferritin, in bone marrow and liver of patients with adult onset Still's disease, developing ma…

2015

In this paper, we aimed to evaluate the levels of ferritin enriched in H subunits (H-ferritin) and ferritin enriched in L subunits (L-ferritin) and the cells expressing these 2 molecules, in the bone marrow (BM) and liver biopsies obtained from adult onset Still's disease (AOSD) patients who developed macrophage activation syndrome (MAS), and correlating these data with the severity of the disease. Twenty-one patients with MAS-associated AOSD underwent BM biopsy and among them, 9 patients with hepatomegaly and elevated liver enzymes underwent liver biopsy. All the samples were stained by both immunohistochemistry and immunofluorescence. A statistical analysis was performed to estimate the p…

Dissecting the clinical heterogeneity of adult-onset Still's disease, results from a multi-dimensional characterisation and stratification

2021

Abstract Objectives To stratify adult-onset Still’s disease (AOSD) patients in distinct clinical subsets to be differently managed, by using a multi-dimensional characterization. Methods AOSD patients were evaluated by using a hierarchical unsupervised cluster analysis comprising age, laboratory markers systemic score and outcomes. The squared Euclidean distances between each pair of patients were calculated and put into a distance matrix, which served as the input clustering algorithm. Derived clusters were descriptively analysed for any possible difference. Results Four AOSD patients clusters were identified. Disease onset in cluster 1 was characterized by fever (100%), skin rash (92%) an…

Mesenchymal stem cells of Systemic Sclerosis patients, derived from different sources, show a profibrotic microRNA profiling

2019

AbstractSystemic Sclerosis (SSc) is a disease with limited therapeutic possibilities. Mesenchymal stem cells (MSCs)-therapy could be a promising therapeutic option, however the ideal MSCs source has not yet been found. To address this problem, we perform comparison between bone marrow (BM)-MSCs and adipose (A)-MSCs, by the miRs expression profile, to identify the gene modulation in these two MSCs source. MicroRNAs (miRs) are RNAs sequences, regulating gene expression and MSCs, derived from different tissues, may differently respond to the SSc microenvironment. The miRs array was used for the miRs profiling and by DIANA-mirPath tool we identified the biological functions of the dysregulated …

Possible role for IL-40 and IL-40-producing cells in the lymphocytic infiltrated salivary glands of patients with primary Sjögren's syndrome

2023

ObjectivesAim of this study was to investigate the expression of interleukin (IL)-40, a new cytokine associated with B cells homoeostasis and immune response, in primary Sjögren syndrome (pSS) and in pSS-associated lymphomas.Methods29 patients with pSS and 24 controls were enrolled. Minor salivary gland (MSG) biopsies from patients, controls and parotid gland biopsies from pSS-associated lymphoma were obtained. Quantitative gene expression analysis by TaqMan real-time PCR and immunohistochemistry for IL-40 were performed on MSG. MSG cellular sources of IL-40 were determined by flow-cytometry and immunofluorescence. Serum concentration of IL-40 was assessed by ELISA and cellular sources of I…

H-ferritin and CD68+/H-ferritin+ monocytes/macrophages are increased in the skin of adult-onset Still's disease patients and correlate with the multi…

2016

Summary Adult-onset Still's disease (AOSD) patients may show an evanescent salmon-pink erythema appearing during febrile attacks and reducing without fever. Some patients may experience this eruption for many weeks. During AOSD, exceptionally high serum levels of ferritin may be observed; it is an iron storage protein composed of 24 subunits, heavy (H) subunits and light (L) subunits. The ferritin enriched in L subunits (L-ferritin) and the ferritin enriched in H subunits (H-ferritin) may be observed in different tissues. In this work, we aimed to investigate the skin expression of both H-and L-ferritin and the number of macrophages expressing these molecules from AOSD patients with persist…

Perivascular Cells in Diffuse Cutaneous Systemic Sclerosis Overexpress Activated ADAM12 and Are Involved in Myofibroblast Transdifferentiation and De…

2016

Objective.Microvascular damage is pivotal in the pathogenesis of systemic sclerosis (SSc), preceding fibrosis, and whose trigger is not still fully understood. Perivascular progenitor cells, with profibrotic activity and function, are identified by the expression of the isoform 12 of ADAM (ADAM12) and this molecule may be upregulated by transforming growth factor-β (TGF-β). The goal of this work was to evaluate whether pericytes in the skin of patients with diffuse cutaneous SSc (dcSSc) expressed ADAM12, suggesting their potential contribution to the fibrotic process, and whether TGF-β might modulate this molecule.Methods.After ethical approval, mesenchymal stem cells (MSC) and fibroblasts …

Monocytes from patients with rheumatoid arthritis and type 2 diabetes mellitus display an increased production of interleukin (IL)-1β via the nucleot…

2015

Summary A better understanding about the mechanisms involved in the pathogenesis of type 2 diabetes mellitus (T2D) showed that inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin (IL)-1β play a pivotal role, mirroring data largely reported in rheumatoid arthritis (RA). IL-1β is produced mainly by monocytes (MO), and hyperglycaemia may be able to modulate, in the cytoplasm of these cells, the assembly of a nucleotide-binding domain and leucine-rich repeat containing family pyrin (NLRP3)-inflammosome, a cytosolic multi-protein platform where the inactive pro-IL-1β is cleaved into active form, via caspase-1 activity. In this paper, we evaluated the production of IL-1 β …

Parenchymal lung disease in adult onset Still’s disease: an emergent marker of disease severity—characterisation and predictive factors from Gruppo I…

2020

Abstract Background Adult-onset Still’s disease (AOSD) is a systemic inflammatory disorder of unknown aetiology usually affecting young adults. Interestingly, recent evidence from the juvenile counterpart of AOSD suggested the emergent high fatality rate of lung disease (LD) in these patients. In this work, we aimed to characterise LD in AOSD, to identify associated clinical features and predictive factors, and to describe long-term outcomes of the disease comparing patients with LD and those without. Methods A retrospective assessment of prospectively followed patients, from January 2001 to December 2019, was provided to describe the rate of LD in AOSD, associated clinical features and pre…

Disparities in the prevalence of clinical features between systemic juvenile idiopathic arthritis and adult-onset Still's disease

2022

Abstract Objective To compare clinical features and treatments of patients with systemic JIA (sIJA) and adult-onset Still’s disease (AOSD). Methods The clinical charts of consecutive patients with sJIA by International League of Association of Rheumatology criteria or AOSD by Yamaguchi criteria were reviewed. Patients were seen at a large paediatric rheumatology referral centre or at 10 adult rheumatology academic centres. Data collected included clinical manifestations, inflammation biomarkers, systemic score, macrophage activation syndrome (MAS), parenchymal lung disease, disease course, disability, death and medications administered. Results A total of 166 patients (median age at diagnos…

H-ferritin and proinflammatory cytokines are increased in the bone marrow of patients affected by macrophage activation syndrome

2017

Summary Macrophage activation syndrome (MAS) is hyperinflammatory life-threatening syndrome, associated typically with high levels of serum ferritin. This is an iron storage protein including heavy (H) and light (L) subunits, categorized on their molecular weight. The H-/L subunits ratio may be different in tissues, depending on the specific tissue and pathophysiological status. In this study, we analysed the bone marrow (BM) biopsies of adult MAS patients to assess the presence of: (i) H-ferritin and L-ferritin; (ii) CD68+/H-ferritin+ and CD68+/L-ferritin+; and (iii) interleukin (IL)-1β, tumour necrosis factor (TNF) and interferon (IFN)-γ. We also explored possible correlations of these re…

Erratum to “Is minor salivary gland biopsy more than a diagnostic tool in primary Sjo¨gren’s syndrome? Association between clinical, histopathologica…

2015

Interstitial lung disease in systemic sclerosis: current and future treatment.

2017

Systemic sclerosis (SSc) has the highest fatality rate among connective tissue diseases and is characterized by vascular damage, inflammation and fibrosis of the skin and various internal organs. Interstitial lung disease (ILD) frequently complicates SSc and can be a debilitating disorder with a poor prognosis. ILD is the most frequent cause of death in SSc, and the management of SSc–ILD patients is a great challenge. Early detection of pulmonary involvement based on a recent decline of lung function tests and on the extent of lung involvement at high-resolution computed tomography is critical for the best management of these patients. This article summarizes classification, pathogenesis,…

Mesenchymal stromal cells and rheumatic diseases: new tools from pathogenesis to regenerative therapies

2015

In recent years, mesenchymal stromal cells (MSCs) have been largely investigated and tested as a new therapeutic tool for several clinical applications, including the treatment of different rheumatic diseases. MSCs are responsible for the normal turnover and maintenance of adult mesenchymal tissues as the result of their multipotent differentiation abilities and their secretion of a variety of cytokines and growth factors. Although initially derived from bone marrow, MSCs are present in many different tissues such as many peri-articular tissues. MSCs may exert immune-modulatory properties, modulating different immune cells in both in vitro and in vivo models, and they are considered immune-…

Prevalence of type 2 diabetes and impaired fasting glucose in patients affected by rheumatoid arthritis: Results from a cross-sectional study.

2017

Abstract Although the better management of rheumatoid arthritis (RA) has significantly improved the long-term outcome of affected patients, a significant proportion of these may develop associated comorbidities including cardiometabolic complications. However, it must be pointed out that a comprehensive cardiometabolic evaluation is still poorly integrated into the management of RA patients, due to a limited awareness of the problem, a lack of appropriate clinical studies, and optimal strategies for cardiovascular (CV) risk reduction in RA. In addition, although several studies investigated the possible association between traditional CV risk factors and RA, conflicting results are still av…

Guidelines for biomarkers in autoimmune rheumatic diseases - evidence based analysis

2018

Autoimmune rheumatic diseases are characterised by an abnormal immune system response, complement activation, cytokines dysregulation and inflammation. In last years, despite many progresses in managing these patients, it has been shown that clinical remission is reached in less than 50% of patients and a personalised and tailored therapeutic approach is still lacking resulting in a significant gap between guidelines and real-world practice. In this context, the need for biomarkers facilitating early diagnosis and profiling those individuals at the highest risk for a poor outcome has become of crucial interest. A biomarker generally refers to a measured characteristic which may be used as a…

Interleukin-32 in systemic sclerosis, a potential new biomarker for pulmonary arterial hypertension

2020

Abstract Background Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc), associated with a progressive elevation in pulmonary vascular resistance and subsequent right heart failure and death. Due to unspecific symptoms, the diagnosis of PAH is often delayed. On this basis, it is of great value to improve current diagnostic methods and develop new strategies for evaluating patients with suspected PAH. Interleukin-32 (IL-32) is a proinflammatory cytokine expressed in damaged vascular cells, and the present study aimed to assess if this cytokine could be a new biomarker of PAH during SSc. Methods The IL-32 expression was evaluated in the sera and skin sam…

Adult-onset Still’s disease: evaluation of prognostic tools and validation of the systemic score by analysis of 100 cases from three centers

2016

Background: Adult-onset Still's disease (AOSD) is rare inflammatory disease of unknown etiology that usually affects young adults. The more common clinical manifestations are spiking fevers, arthritis, evanescent rash, elevated liver enzymes, lymphadenopathy, hepatosplenomegaly, and serositis. The multi-visceral involvement of the disease and the different complications, such as macrophage activation syndrome, may strongly decrease the life expectancy of AOSD patients. Methods: This study aimed to identify the positive and negative features correlated with the outcome of patients. A retrospective analysis of AOSD patients prospectively admitted to three rheumatologic centers was performed t…

FRI0613 H-ferritin and pro-inflammatory cytokines are increased in the bone marrow of adult patients affected by macrophage activation syndrome

2017

Background During macrophage activation syndrome (MAS), an inflammatory life-threatening syndrome, extremely high levels of serum ferritin may be observed [1]. Ferritin is an intracellular iron storage protein comprising 24 subunits that may be divided in heavy (H) subunits and light (L) subunits, based on their molecular weight [2]. The H-/L-subunits ratio may change, depending on the specific tissue and the physiologic status of the cell. In the normal condition, ferritin enriched in L subunits (L-ferritin) has been found in the liver and in the spleen, whereas the ferritin enriched in H subunits (H-ferritin), may be mainly observed in the heart and kidneys [2]. Objectives We investigated…

FRI0504 Prognostic Factors of Adult Onset Still's Disease: Analysis of 100 Cases in 3 Tertiary Referral Centers

2016

Background Adult onset Still9s disease (AOSD) is rare inflammatory disease [1]. Three different patterns of AOSD have been identified: i. monocyclic pattern, characterized by a systemic single episode; ii. polycyclic pattern, associated with multiple flares, separated by remissions; iii. chronic pattern, related to a persistently active disease with associated polyarthritis [2]. Until now, the treatment of AOSD remains largely empirical, lacking controlled clinical trials [1]. Objectives We aimed to investigate clinical data of AOSD patients and any possible correlation among these features and the outcome of patients. Methods Clinical data of 100 AOSD patients were recorded. All patients f…

Managing Adult-onset Still's disease: The effectiveness of high-dosage of corticosteroids as first-line treatment in inducing the clinical remission.…

2019

Abstract To assess the effectiveness of the treatment with high dosage of corticosteroids (CCSs), as first-line therapy, in inducing remission in naïve Adult-onset Still's disease (AOSD) patients compared with low dosage of CCSs, after 6 months. To further evaluate the rate of patients maintaining the remission and the rate of CCSs discontinuation, after additional 12 months of follow-up. A retrospective evaluation of patients prospectively followed was designed to compare the rate of clinical remission in naïve AOSD patients treated with high dosages of CCSs (0.8–1 mg/kg/day of prednisone-equivalent) or low dosage of CCSs (0.2–0.3 mg/kg/day of prednisone-equivalent), after 6 months. An add…

Blocking Jak/STAT signalling using tofacitinib inhibits angiogenesis in experimental arthritis

2021

Abstract Objective During rheumatoid arthritis (RA), the angiogenic processes, occurring with pannus-formation, may be a therapeutic target. JAK/STAT-pathway may play a role and the aim of this work was to investigate the inhibiting role of a JAK-inhibitor, tofacitinib, on the angiogenic mechanisms occurring during RA. Methods After ethical approval, JAK-1, JAK-3, STAT-1, STAT-3 and VEGF expression was evaluated on RA-synovial-tissues. In vitro, endothelial cells (ECs), stimulated with 20 ng/ml of VEGF and/or 1 μM of tofacitinib, were assessed for tube formation, migration and proliferation, by Matrigel, Boyden chamber assay and ki67 gene-expression. In vivo, 32 mice received collagen (coll…

IL-1β at the crossroad between rheumatoid arthritis and type 2 diabetes: may we kill two birds with one stone?

2016

ABSTRACT: Although in the past the prevention of joint destruction in rheumatoid arthritis (RA) was strongly emphasized, now a great interest is focused on associated comorbidities in these patients. Multiple data suggest that a large percentage of RA patients are affected by Type 2 Diabetes (T2D), whose incidence has reached epidemic levels in recent years, thus increasing the health care costs. A better knowledge about the pathogenesis of these diseases as well as the mechanisms of action of drugs may allow both policy designers and physicians to choose the most effective treatments, thus lowering the costs. This review will focus on the role of Interleukin (IL)-1β in the pathogenesis of …

Advances in immunopathogenesis of macrophage activation syndrome during rheumatic inflammatory diseases: toward new therapeutic targets?

2017

Introduction: Macrophage activation syndrome (MAS) is a severe, hyperinflammatory life-threatening syndrome, generally complicating different rheumatic diseases. Despite the severity of the disease, little is known about the pathogenic mechanisms and, thus, possible targeted therapies in the management of these patients. Areas covered: In this review, we aimed to update the current pathogenic knowledge of MAS, during rheumatic diseases, focusing mainly on immunologic abnormalities and on new possible therapeutic strategies. Expert commentary: The difficult pathogenic scenario of MAS, in which genetic defects, predisposing diseases, and triggers are mixed together with the high mortality rat…

International consensus: What else can we do to improve diagnosis and therapeutic strategies in patients affected by autoimmune rheumatic diseases (r…

2017

Autoimmune diseases are a complex set of diseases characterized by immune system activation and, although many progresses have been done in the last 15 years, several unmet needs in the management of these patients may be still identified. Recently, a panel of international Experts, divided in different working groups according to their clinical and scientific expertise, were asked to identify, debate and formulate a list of key unmet needs within the field of rheumatology, serving as a roadmap for research as well as support for clinicians. After a systematic review of the literature, the results and the discussions from each working group were summarised in different statements. Due to th…

THU0582 Prognostic Factors of Macrophage Activation Syndrome in Adults: Analysis of 40 Cases in 2 Tertiary Referral Centers

2016

Background Macrophage activation syndrome (MAS) is a rare, life-threatening disease in which early diagnosis and aggressive therapeutic strategy may improve the outcome [1]. Due to its rarity, epidemiologic data are still lacking. Hyperferritinemia is frequently associated with MAS and might modulate the cytokines storm the latter contributing to the development of multi-organ failure [2]. Objectives In the current study, we aimed to investigate clinical data, treatments, and outcome of adult MAS patients secondary to autoimmune rheumatic disease. Methods We retrospectively investigated clinical data, treatments, and outcome of 40 adult MAS patients secondary to autoimmune rheumatic disease…

AB0630 Cardiac Magnetic Resonance Imaging with Pharmacological Stress Perfusion in Asymptomatic Patients with Systemic Sclerosis

2016

Background Systemic Sclerosis (SSc)-heart disease (SSc-HD), although often clinically silent, significantly reduces the life-expectancy in these patients [1]. The cardiac magnetic resonance (CMR) is recognized useful tool for the diagnosis of SSc-HD and cardiac stress tests might be a helpful technique to highlight the occult myocardial involvement, which cannot be detected at rest due to compensatory mechanisms [2,3]. Objectives To evaluate the possible occult cardiac involvement in asymptomatic SSc patients by pharmacological stress, rest perfusion and delayed enhancement CMR, to identify as earlier as possible those patients at higher risk of cardiac related mortality and needing specifi…

Pharmacological stress, rest perfusion and delayed enhancement cardiac magnetic resonance identifies very early cardiac involvement in systemic scler…

2017

Objective To evaluate occult cardiac involvement in asymptomatic systemic sclerosis (SSc) patients by pharmacological stress, rest perfusion and delayed enhancement cardiac magnetic resonance (CMR), for a very early identification of patients at higher risk of cardiac-related mortality. Methods Sixteen consecutive patients with definite SSc, fulfilling the American College of Rheumatology/European League Against Rheumatism 2013 classification criteria in less than 1 year from the onset of Raynaud's phenomenon, underwent pharmacological stress, rest perfusion and delayed enhancement CMR. At enrollment, no patient showed signs and/or symptoms suggestive for cardiac involvement. No patient sho…

Persistence of C-reactive protein increased levels and high disease activity are predictors of cardiovascular disease in patients with axial spondylo…

2022

AbstractAn accurate prediction of cardiovascular (CV) risk in patients with Axial Spondyloarthritis (axSpA) is a strong unmet need, as CV risk algorithms poorly perform in these subjects. The aim of this study was to establish whether the persistence of high C-reactive protein (CRP) and high disease activity may be considered predictive factors of CVD in axSpA. 295 patients without personal history of CVD, were consecutively enrolled in this study. To evaluate the relationship between CV events occurrence (fatal and non-fatal) and the persistence of increased CRP levels, ASDAS (Ankylosing Spondylitis Disease Activity Score) > 2.1, and BASDAI (Bath Ankylosing Spondylitis Disease Activity)…

Cardiovascular disease in primary sjögren’s syndrome

2018

Background A close relationship between rheumatic diseases and cardiovascular disease (CVD) has been reported, accounting for the higher mortality and morbidity observed in these patients. In the last years, it has been clearly reported that patients affected by primary Sjogren's syndrome (pSS) experienced an increased risk of CVD. Objective This review aimed at investigating CVD, traditional cardiovascular (CV) risk factors and possible targeted therapeutic strategies in pSS patients. Method Available literature concerning CV risk factors in pSS patients has been selected and discussed. Conclusion Disease-related characteristics and traditional CV risk factors contribute to observed athero…

Prognostic factors of macrophage activation syndrome, at the time of diagnosis, in adult patients affected by autoimmune disease: Analysis of 41 case…

2016

Macrophage activation syndrome (MAS) is a rare, life-threatening disease in which early diagnosis and aggressive therapeutic strategy may improve the outcome. Due to its rarity, epidemiologic data are still lacking. Hyperferritinemia is frequently associated with MAS and might modulate the cytokine storm, which is involved in the development of multiple organ failure. In this paper, we investigated clinical data, treatments, and outcome of a homogeneous cohort of 41 adult MAS patients, complicating autoimmune rheumatic diseases. MAS-related death occurred in 17 patients (42.5%) during the follow-up, and older age and increased serum ferritin levels, at the time of diagnosis, were significan…

Is minor salivary gland biopsy more than a diagnostic tool in primary Sjorgren's syndrome? Association between clinical, histopathological, and molec…

2014

Objectives: Several histological scoring systems, including the focus score, performed in minor salivary glands (MSGs) by hematoxylin-eosin (H&E) staining, have been employed in clinical practice to assess the inflammatory infiltrate and provide the diagnosis of primary Sjorgren's syndrome (pSS). Aims of this study were to integrate different scoring systems and identify potential differences in the molecular profile of lymphoid cytokines related to germinal center (GC) formation and clinical subsets in pSS. Methods: Overall, 104 pSS patients and 40 subjects with sicca non-pSS were retrospectively evaluated. MSG biopsies were evaluated by H&E and immunofluorescence to assess histological pa…

AB0919 H-Ferritin and CD68+/H-ferritin+ Cells Are Increased in The Skin of Adult Onset Still's Disease Patients and Correlate with The Disease Activi…

2016

Background Adult onset Still9s disease (AOSD) is an inflammatory disease, characterized by high spiking fevers, arthritis, salmon-pink erythema and multivisceral involvement [1]. During AOSD, exceptionally high serum levels of ferritin may be observed and they might contribute to production of proinflammatory molecules [2]. Ferritin is composed by 24 subunits, heavy (H) subunits and light (L) subunits. The ferritin enriched in L subunits (L-ferritin) and the ferritin enriched in H subunits (H-ferritin) may be recognized in different tissues [3]. Objectives To investigate the skin tissue expression of both H-and L-ferritin and the number of macrophages expressing these molecules, in the infl…

Efficacy and safety of rituximab treatment in early primary Sjögren's syndrome: a prospective, multi-center, follow-up study.

2013

Introduction Primary Sjögren’s syndrome (pSS) is an autoimmune disorder affecting exocrine glands; however, a subgroup of pSS patients experience systemic extra-glandular involvement leading to a worsening of disease prognosis. Current therapeutic options are mainly empiric and often translated by other autoimmune diseases. In the last few years growing evidence suggests that B-cell depletion by rituximab (RTX) is effective also in pSS. Patients with early active disease appear to be those who could benefit the most from RTX. The aim of this study was to investigate the efficacy and safety of RTX in comparison to disease modifying anti-rheumatic drugs (DMARDs) in early active pSS patients. …

The CD68+/H-ferritin+ cells colonize the lymph nodes of the patients with adult onset Still's disease and are associated with increased extracellular…

2015

Summary In this work, we aimed to evaluate the levels of ferritin enriched in H subunits (H-ferritin) and ferritin enriched in L subunits (L-ferritin) and the cells expressing these two molecules in the lymph node (LN) biopsies obtained from adult-onset Still's disease (AOSD) patients, and the possible correlation among these data and the severity of the disease. Ten patients with AOSD underwent LN biopsy. All the samples were stained by immunofluorescence. A statistical analysis was performed to estimate the possible correlation among both H-ferritin and L-ferritin tissue expression and the clinical picture of the disease. Furthermore, the same analysis was performed to evaluate the possib…

Impact of smoking habit on adult-onset Still’s disease prognosis, findings from a multicentre observational study

2021

The objective of this study is to describe the possible prognostic impact of smoking habit on adult-onset Still’s disease (AOSD) patients, by the assessment of clinical characteristics, life-threatening complications occurrence, and mortality in smokers than non-smokers. A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was conducted. Out of 185 AOSD assessed patients, 45 smokers were identified. These showed a higher frequency of pericarditis (35.5% vs 16.4%, p = 0.011), pleuritis (33.3% vs 14.3%, p = 0.008), and abdominal pain (17.7% vs 6.4%, p = 0.035). Furthermore, sm…

Blocking CD248 molecules in perivascular stromal cells of patients with systemic sclerosis strongly inhibits their differentiation toward myofibrobla…

2018

Abstract Background Fibrosis may be considered the hallmark of systemic sclerosis (SSc), the end stage triggered by different pathological events. Transforming growth factor-β (TGF-β) and platelet-derived growth factor BB (PDGF-BB) are profibrotic molecules modulating myofibroblast differentiation and proliferation, respectively. There is evidence linking CD248 with these two molecules, both highly expressed in patients with SSc, and suggesting that CD248 may be a therapeutic target for several diseases. The aim of this work was to evaluate the expression of CD248 in SSc skin and its ability to modulate SSc fibrotic process. Methods After ethical approval was obtained, skin biopsies were co…

The emerging role of IL-1 inhibition in patients affected by rheumatoid arthritis and diabetes

2018

Background Although in the past, prevention of the joint destruction and disability was strongly emphasised in Rheumatoid Arthritis (RA), at present, a growing body of evidence is focused at identifying the best management of associated comorbidities, such as Type 2 Diabetes (T2D). Recently, the hypothesis that blocking pro-inflammatory activity may be helpful in the treatment of some comorbidities has been proposed in RA patients. Objective We reviewed the role of IL-1β during RA and T2D, the efficacy of IL-1 blocking agents in controlling both diseases and, possible, decreasing the concomitant enhanced atherosclerotic process. Method After literature search, the available evidence has bee…

The growing role of precision medicine for the treatment of autoimmune diseases; results of a systematic review of literature and Experts’ Consensus

2021

International audience; Autoimmune diseases (AIDs) share similar serological, clinical, and radiological findings, but, behind these common features, there are different pathogenic mechanisms, immune cells dysfunctions, and targeted organs. In this context, multiple lines of evidence suggest the application of precision medicine principles to AIDs to reduce the treatment failure. Precision medicine refers to the tailoring of therapeutic strategies to the individual characteristics of each patient, thus it could be a new approach for management of AIDS which considers individual variability in genes, environmental exposure, and lifestyle. Precision medicine would also assist physicians in ch…

Additional file 2 of Blocking Jak/STAT signalling using tofacitinib inhibits angiogenesis in experimental arthritis

2021

Additional file 2: Supplementary material 2. Arthritis score evaluation. The histogram showed the median and the range of the arthritis score evaluated the day 35. The collagen induced a significant increase of arthritis score when compared to control group, and 30 mg/Kg/day of tofacitinib prevented the increase of arthritis score (**=p=0.001; ***= p

Additional file 1 of Blocking Jak/STAT signalling using tofacitinib inhibits angiogenesis in experimental arthritis

2021

Additional file 1: Supplementary material 1. Mice treatments. The first day (day 0) of the procedure, 64 DBA/1 J mice were divided in 2 groups. One control group (n=32) receiving saline solution and one CIA group (n=32) receiving 100 μg of bovine type II collagen, emulsified with an equal volume of Freund’s complete adjuvant. After 18 days, the control group received saline solution and CIA mice received type II collagen and Freund’s incomplete adjuvant. At the day 19, controls and CIA mice were divided into 2 subgroups: one receiving vehicle (n=16) and one receiving 30 mg/kg/day of tofacitinib (n=16). After 35 days the first collagen administration, the mice were sacrificed and the blood c…