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…

Interleukin-9 Overexpression and Th9 Polarization Characterize the Inflamed Gut, the Synovial Tissue, and the Peripheral Blood of Patients With Psori…

2016

Objective To investigate the expression and tissue distribution of Th9-related cytokines in patients with psoriatic arthritis (PsA). Methods Quantitative gene expression analysis of Th1, Th17, and Th9 cytokines was performed in intestinal biopsy samples obtained from patients with PsA, HLA-B27-positive patients with ankylosing spondylitis (AS), patients with Crohn's disease (CD), and healthy controls. Expression and tissue distribution of interleukin-23 (IL-23), IL-17, IL-22, IL-9, and IL-9 receptor (IL-9R) were evaluated by immunohistochemistry and confocal microscopy. Flow cytometry was used to study the frequency of Th9 cells among peripheral blood, lamina propria, and synovial fluid mon…

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 …

Macrophage Activation Syndrome in Patients Affected by Adult-onset Still Disease: Analysis of Survival Rates and Predictive Factors in the Gruppo Ita…

2018

Objective.Macrophage activation syndrome (MAS) is a reactive form of hemophagocytic lymphohistiocytosis, which can complicate adult-onset Still disease (AOSD). We investigated AOSD clinical features at the time of diagnosis, to assess predictors of MAS occurrence. Further, we analyzed the outcomes of patients with AOSD who experience MAS.Methods.Patients with AOSD admitted to any Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale center were retrospectively analyzed for features typical of AOSD, MAS occurrence, and their survival rate.Results.Of 119 patients with AOSD, 17 experienced MAS (12 at admission and 5 during followup). Twelve patients with MAS at first admission diff…

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…

Development and implementation of the AIDA international registry for patients with Still's disease

2022

ObjectiveAim of this paper is to present the design, construction, and modalities of dissemination of the AutoInflammatory Disease Alliance (AIDA) International Registry for patients with systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), which are the pediatric and adult forms of the same autoinflammatory disorder.MethodsThis Registry is a clinical, physician-driven, population- and electronic-based instrument implemented for the retrospective and prospective collection of real-world data. The collection of data is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain evidence drawn from routine patients' management. The co…

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 …

Adult-onset Still's disease with elderly onset: results from a multicentre study

2021

Objective In this study, we aimed to describe the clinical characteristics, life-threatening complications occurrence, and mortality of adult-onset Still's disease (AOSD) patients with elderly onset. Methods A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was performed. Results Out of 221 assessed patients, 37 (16.7%) had an onset of the disease aged over 60 years. When compared with younger patients, these were characterised by a higher prevalence of pericarditis (p=0.008), comorbidities (p < 0.0001), and mortality (p=0.023). Age predicted the presence of serositis …

Subclinical and clinical atherosclerosis in rheumatoid arthritis: results from the 3-year, multicentre, prospective, observational GIRRCS (Gruppo Ita…

2019

Background Rheumatoid arthritis (RA) is associated with an increased risk of morbidity and mortality, when compared with general population, largely due to enhanced atherosclerotic disease. In this work, we aimed at assessing both occurrence and predictive factors of subclinical and clinical atherosclerosis in RA. Methods From January 1, 2015, to December 31, 2015, consecutive participants with RA, admitted to Italian Rheumatology Units, were assessed in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort. After that, those participants were followed up in a 3-year, prospective, observational study, assessing the occurrence of subclinical and clinical ather…

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 …

Ferritin and C-reactive protein are predictive biomarkers of mortality and macrophage activation syndrome in adult onset Still's disease. Analysis of…

2020

ObjectiveTo assess the predictive role of ferritin and C-reactive protein (CRP) on occurrence of macrophage activation syndrome (MAS) and mortality in patients with adult onset Still's disease (AOSD), a rare and severe disease, included in the multicentre Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort.MethodsThe predictive role, at the time of diagnosis, of serum levels of ferritin and CRP on occurrence of MAS and mortality, was evaluated by logistic regression analyses and receiver-operating characteristic (ROC) curves were built to identify patients at high risk of MAS and mortality, respectively.ResultsIn assessed 147 patients with AOSD, levels of ferri…

OP0081 Aberrant Expression of IL-22RA1 on Hematopoietic Cells as Immunologically Signature of Primary Sjogren’s Syndrome and Sjogren-Associated Non-H…

2013

Background Interleukin (IL)-22 is a potent mediator of cellular inflammatory responses that has been recently reported to play a role in the pathogenesis of primary Sjogren’s Syndrome (p-SS) (1, 2) and of T and B lymphomas. IL-22 biological activity is initiated by binding to a cell-surface complex composed of two subunits, IL-22R1 and IL-10R2 receptor chains, and further regulated by interactions with a soluble binding protein, IL-22BP. Unlike the IL-10R2, which is constitutively expressed in many human tissues, IL-22R1 is not detectable in immune cells. Objectives Aim of this study was to better characterize the role of IL-22 axis in the pathogenesis of p-SS and p-SS-associated lymphomas.…

SAT0025 MIR 106A, MIR 19A-B, MIR 20A and MIR21A regulate vγ9vδ2 functions participating in the inflammatory responses occurring in rheumatoid arthrit…

2017

Background miRNAs are non-coding RNAs which have significant roles in regulating gene expression. The miR17-92 cluster appears to be a key factor in the inflammatory pathways activated during RA. Objectives In this study we aimed to evaluate miR17–92 expression and functions in γδ T cell subsets in RA patients, γδ T cells, in fact produce proinflammatory cytokines such as IFN-g, IL-6 and IL-8 that may contribute to the inflammatory responses in RA. Methods Heparinized peripheral blood from 10 early RA untreated patients and 10 healthy donors was obtained for this study. Polyclonal Vγ9Vδ2 T cell lines were generated first by magnetic isolation followed by sorting (FACSAria) and further analy…

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…

Downregulation of miRNA17-92 cluster marks Vγ9Vδ2 T cells from patients with rheumatoid arthritis

2018

Abstract Background We aimed to evaluate the phenotype, function, and microRNA (miRNA)17–92 cluster expression in Vγ9Vδ2 T-cell subsets and the correlation with immune response in rheumatoid arthritis (RA) patients. Methods Peripheral blood from 10 early RA untreated patients and 10 healthy donors (HD) was obtained. Polyclonal Vγ9Vδ2 T-cell lines were generated and analysed by flow cytometry. Analysis of miRNA17–92 cluster expression was performed by real-time polymerase chain reaction (RT-PCR), and expression of mRNA target genes was also studied. Results A remarkable change in the distribution of Vγ9Vδ2 T-cell functional subsets was observed in the peripheral blood of RA patients compared…

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…

Interleukin (IL)-22 receptor 1 is over-expressed in primary Sjogren's syndrome and Sjögren-associated non-Hodgkin lymphomas and is regulated by IL-18.

2015

Summary The aim of this study was to elucidate more clearly the role of interleukin (IL)-18 in modulating the IL-22 pathway in primary Sjögren's syndrome (pSS) patients and in pSS-associated lymphomas. Minor salivary glands (MSGs) from patients with pSS and non-specific chronic sialoadenitis (nSCS), parotid glands biopsies from non-Hodgkin lymphomas (NHL) developed in pSS patients, were evaluated for IL-18, IL-22, IL-22 receptor 1 (IL-22R1), IL-22 binding protein (IL-22BP) and signal transducer and activator of transcription-3 (STAT-3) expression. MSGs IL-22R1-expressing cells were characterized by confocal microscopy and flow cytometry in pSS, nSCS and healthy controls. The effect of recom…

THU0231 IL-17 polarization of mait cells derive from the activation of two different pathways

2017

Background Primary Sjogren Syndrome (pSS) is a chronic inflammatory disorder affecting exocrine glands. Both IL-23 and the downstream cytokines IL-17 and IL-22 are recognised as key players in the disease. Therefore, the identification of the cellular sources and inducers of IL-17 is crucial in the understanding of the drivers of inflammation in pSS. Mucosal-associated invariant T (MAIT) cells recognize riboflavin derivatives presented by the MHC class I-like molecule MR1. Objectives Recently, MAIT cells have been implicated in the pathogenesis of autoimmune disorders and found expanded in salivary glands of pSS patients. Their expression of IL7R and IL23R, makes them potential contributors…

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-…

Interleukin-9 over-expression and T helper 9 polarization in systemic sclerosis patients.

2017

Summary T helper 9 (Th9) cells and interleukin (IL)-9 are involved in the pathogenesis of several autoimmune diseases. The exact role of IL-9 and Th9 cells in patients with systemic sclerosis (SSc) have not yet been studied adequately. IL-9, IL-9R, transcription factor PU.1 (PU.1), IL-4, thymic stromal lymphopoietin (TSLP) and transforming growth factor (TGF)-β expression were assessed in skin and kidney biopsies of SSc patients and healthy controls (HC) by immunohistochemistry (IHC). The cellular source of IL-9 was also analysed by confocal microscopy analysis. Peripheral IL-9-producing cells were also studied by flow cytometry. The functional relevance of IL-9 increased expression in SSc …

OP0090 THE OCCURRENCE OF SUBCLINICAL AND CLINICAL ATHEROSCLEROSIS IN RHEUMATOID ARTHRITIS, RESULTS FROM THE 3-YEAR, MULTICENTER, PROSPECTIVE, OBSERVA…

2019

Background The systemic inflammatory process and the “traditional” cardiovascular (CV) risk factors could synergize the enhancement of CV burden in rheumatoid arthritis (RA) [1]. Objectives To assess the occurrence and the predictive factors of subclinical and clinical atherosclerosis in patients with RA. Methods During 2015, consecutive patients, admitted to Italian Rheumatology Units, were assessed in GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort [2]. After that, patients were followed-up in a 3-year, prospective, observational study, assessing the occurrence of subclinical (carotid and/or peripheral arteries atherosclerotic lesions detected by ultrasou…

Rituximab modulates IL-17 expression in the salivary glands of patients with primary Sjögren's syndrome.

2014

OBJECTIVE: The aim of this study was to evaluate the role of rituximab (RTX) in modulating the expression of the IL-17/IL-23 pathway in the salivary glands (SGs) of patients with primary SS (pSS). METHODS: Consecutive SG biopsies were obtained from 15 patients with pSS before and after 1 year of RTX therapy. The SG expression of IL-17, IL-23p19 and p-STAT3 was evaluated by immunohistochemistry at baseline and after RTX therapy. The role of mast cells in pSS patients in modulating the Th17 response and the immunologic effect of RTX on mast cells were also studied in in vitro experiments. RESULTS: IL-17 was overexpressed in the SGs of patients with pSS mainly by infiltrating T cells and mast …

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…

Occurrence and predictive factors of high blood pressure, type 2 diabetes, and metabolic syndrome in rheumatoid arthritis: findings from a 3-year, mu…

2021

Objectives: In rheumatoid arthritis (RA), "traditional" cardiovascular (CV) risk factors continue to be underdiagnosed and undertreated, thus increasing the risk of developing atherosclerosis. In this work, we evaluated the occurrence and predictive factors of "traditional" cardiovascular risk factors, with a focus on high blood pressure (HBP), type 2 diabetes (T2D), and metabolic syndrome (MetS), in participants with RA, in a 3-year, multicentre, prospective, observational study. Methods: To assess the occurrence and predictive factors of HBP, T2D, and MetS, consecutive participants with RA, admitted to Italian Rheumatology Units, were evaluated in the GIRRCS (Gruppo Italiano di Ricerca in…

Interleukin-25 Axis Is Involved in the Pathogenesis of Human Primary and Experimental Murine Sjögren's Syndrome

2018

Objective To investigate the role of the interleukin-25 (IL-25)/IL-17 receptor B (IL-17RB) axis in experimental Sjogren's syndrome (SS) and in patients with primary SS and primary SS-associated lymphoma. Methods Expression of IL-25, IL-17RB, IL-17B, and tumor necrosis factor receptor-associated factor 6 (TRAF6) was analyzed on minor salivary gland (SG) samples from patients with primary SS and on parotid gland samples from patients with primary SS-associated B cell non-Hodgkin's lymphoma (NHL). IL-17RB expression and the frequencies of natural group 2 innate lymphoid cells (ILC2s), inflammatory ILC2s, and M2-polarized macrophages were assessed by flow cytometry in SG mononuclear cells and p…

Jejunoileal bypass as the main procedure in the onset of immune-related conditions: the model of BADAS

2013

Bariatric surgery represents a common approach for the control of severe morbid obesity, reducing caloric intake by modifying the anatomy of the gastrointestinal tract. Following jejunoileal bypass, a large spectrum of complications has been described, with rheumatic manifestation present in up to 20% of cases. Although bowel bypass syndrome, also called blind loop syndrome, is a well-recognized complication of jejunoileal bypass, the same syndrome was recognized in patients who had not had intestinal bypass surgery, and the term the 'bowel-associated dermatosis-arthritis syndrome' (BADAS) was coined. The pathogenesis of BADAS is as yet poorly understood and only few data concerning this is…

Safety and efficacy of intra-articular anti-tumor necrosis factor α agents compared to corticosteroids in a treat-to-target strategy in patients with…

2015

The aim of this study was to assess safety and efficacy of ultrasonography (US)-guided intra-articular injections using tumor necrosis factor (TNF) blockers compared to corticosteroids in rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients, experiencing refractory monoarthritis despite the current systemic therapy. Eighty-two patients were randomized to receive three intra-articular injections monthly of either corticosteroid or TNF blockers. Primary endpoints were the safety and an improvement greater than 20% for visual analogic scales of involved joint pain in patients injected with anti-TNFα. Further clinical, US, and magnetic resonance imaging (MRI) evaluations were consid…

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 …

Development and Implementation of the AIDA International Registry for Patients With Undifferentiated Systemic AutoInflammatory Diseases

2022

ObjectiveThis paper points out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to pediatric and adult patients affected by Undifferentiated Systemic AutoInflammatory Diseases (USAIDs).MethodsThis is an electronic registry employed for real-world data collection about demographics, clinical, laboratory, instrumental and socioeconomic data of USAIDs patients. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is designed to obtain standardized information for real-life research. The instrument is endowed with flexibility, and it could change over time according to the scientific acquisitions an…

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…

Interleukin-9 and T helper type 9 cells in rheumatic diseases

2016

Summary Interleukin (IL)-9 is a 28-30 kDa monomeric glycosylated polypeptide belonging to the IL-7/IL-9 family of proteins that bind to a composite receptor consisting of the private receptor IL-9R and the IL-2 receptor, gamma (IL-2RG), a common gamma subunit shared by the receptors of many different cytokines. The IL-9R is expressed widely and IL-9 impacts a number of effector cells, such as effector T cells, B cells, innate lymphoid cells, mast cells, polymorphonuclear cells, epithelial cells and smooth muscle cells, playing an important role in regulating inflammatory immunity. The critical role of IL-9 in promoting cellular and humoral immune responses makes it an important focus of pot…

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…

Rituximab in primary Sjögren's syndrome: a ten-year journey

2014

Primary Sjögren's syndrome (pSS) is an autoimmune disorder affecting exocrine glands and characterized in most cases by a rather mild clinical picture. However, a subgroup of pSS patients experience systemic extraglandular involvement leading to a worsening of disease prognosis. Current therapeutic options for the treatment of pSS are mainly empirical, often translated by other autoimmune diseases, and recent systematic reviews have highlighted the lack of evidence-based recommendations for most of the drugs commonly employed in the spectrum of extraglandular involvement. Because of the well-established role of B-lymphocytes in the pathogenesis of pSS, a B-cell targeting therapy may repres…

Proinflammatory CX3CR1+CD59+Tumor Necrosis Factor–Like Molecule 1A+Interleukin‐23+ Monocytes Are Expanded in Patients With Ankylosing Spondylitis and…

2018

Objective: Gut-derived innate lymphoid cell 3 (ILC3) has been shown to participate in the pathogenesis of ankylosing spondylitis (AS). CX3CR1+ mononuclear phagocytes (MNPs) have been demonstrated to modulate ILC3 function in the gut. This study was undertaken to investigate the role of proinflammatory CX3CR1+CD59+ MNPs in modulating ILC3 function in AS patients. Methods: MNP subsets in the blood of AS patients and controls were analyzed by flow cytometry. The presence of CX3CR1+CD59+ cells in tissue was confirmed by confocal microscopy. Expression of the proinflammatory chemokines CX3CL1 and CCL2 and decoy receptor 6 (DcR-6) was analyzed. Peripheral CX3CR1+CD59+ cells were cocultured with I…

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…

Interleukin (IL)-9/IL-9R axis drives γδ T cells activation in psoriatic arthritis patients

2016

Summary Cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-12, interferon (IFN)-γ, IL-23 and, more recently, IL-9, have been implicated in the initiation/maintenance of inflammation in psoriasis and psoriatic arthritis (PsA). In the present study we aimed to characterize the role of γδ T cells in peripheral blood and synovial fluid of PsA patients and to investigate their response to in-vitro stimulation with antigen or cytokines (IL-9 and IL-23). γδ T cells isolated from peripheral blood mononuclear cells and synovial fluid were analysed by flow cytometry to evaluate the phenotype and cytokine production. IL-23R and IL-9R gene expression were also evaluated by reverse trans…

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…

Rituximab modulates the expression of IL-22 in the salivary glands of patients with primary Sjogren's syndrome

2012

We have recently demonstrated that interleukin (IL)-22, mainly produced by T-helper 17 effector cells, natural killer (NK)p44+NK cells and epithelial cells, may be potentially involved in the pathogenesis of primary Sjogren's syndrome (pSS).1 The IL-22/IL-22R pathway is known to play a role in the emergence of T and B-cell lymphoma2 ,3 and pSS is considered a risk factor for the development of lymphoma.4 Rituximab, which has historically been used for the treatment of B-cell lymphoma,5 has also been considered to be effective in the therapy of pSS.6 Ten consecutive patients with pSS (eight women and two men, with a mean duration of disease of 48±18 months), diagnosed according to the Americ…

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. …

Efficacy and safety of tocilizumab in adult-onset Still's disease: Real-life experience from the international AIDA registry

2022

© 2022 Elsevier Inc.Background/objectives: Long-term efficacy and safety of tocilizumab (TCZ) in adult-onset Still's disease (AOSD) mostly derive from small case series. Herein we report a registry-based study investigating TCZ efficacy and safety in a cohort of patients with AOSD evaluated by clinical and serum inflammatory markers as well as drug retention rate analysis. Methods: This is an international multicentre study analyzing data from patients with AOSD regularly enrolled in the AIDA registry. TCZ efficacy was evaluated between baseline and last follow-up assessment in terms of changes in the Pouchot score and laboratory findings. Drug-retention rate was estimated by the Kaplan-Mei…

Endothelial progenitor cells: Are they displaying a function in autoimmune disorders?

2016

Endothelial Progenitor Cells (EPCs) are bone marrow derived cells able to differentiate in mature endothelial cells (EC) contributing to the generation of new vessels, connecting to fibronectin, and forming colonies and/or colony forming units. Since circulating EPCs can be actively considered part of endothelial damage in several cardiovascular diseases and autoimmune disorders the possibility to have a measure for endothelium damage should be considered of interest to predict the patient out-come. At the same time the EPCs proliferative and regenerative role could be considered for therapeutic applications. Studies have been performed to elucidate the role of EPCs in Systemic Sclerosis an…

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…

IL-9 IN PsA

2016

Objective. To investigate the expression and tis- sue distribution of Th9-related cytokines in patients with psoriatic arthritis (PsA). Methods. Quantitative gene expression analysis of Th1, Th17, and Th9 cytokines was performed in intestinal biopsy samples obtained from patients with PsA, HLA2B272positive patients with ankylosing spondylitis (AS), patients with Crohn’s disease (CD), and healthy controls. Expression and tissue distribu- tion of interleukin-23 (IL-23), IL-17, IL-22, IL-9, and IL-9 receptor (IL-9R) were evaluated by immunohisto- chemistry and confocal microscopy. Flow cytometry was used to study the frequency of Th9 cells among periph- eral blood, lamina propria, and synovial…

THU0260 IL-25 Axis Is Activated and Associated with An ILC2 and M2 Inflammatory State in Patients with Primary Sjogren's Syndrome

2016

Background Type 2 innate lymphoid cells (ILC2) and M2 polarized macrophages are activated and produce cytokines in response to IL-25/IL-17RB, although the relevance of this axis to immune responses in primary Sjoren9s syndrome (pSS) is unknown. Objectives We sought to investigate the role of the IL-25/IL-17RB axis and ILC2 and M2 macrophages in patients with pSS. Methods Expression analysis of IL-17B, IL-25, IL-33 and IL-17RB was performed by TaqMan real-time PCR and immunohistochemistry on salivary glands from 50 patients and 20 controls. Analysis of IL-17RB expression and the frequencies of natural type 2 innate lymphoid cells (nILC2), inflammatory ILC2 (iILC2), and M2-polarized macrophag…

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…

Pro-inflammatory CX3CR1+ CD59+ TL1A+ IL-23+ monocytes are expanded in patients with Ankylosing Spondylitis and modulate ILC3 immune functions

2018

Gut derived ILC3 have been demonstrated to participate in AS pathogenesis. CX3CR1+ mononuclear phagocytes (MNP) have been demonstrated to modulate ILC3 function in the gut. The aim of this study was to study the role of pro-inflammatory CX3CR1+ CD59+ MNP in modulating ILC3 function in AS patients.

Additional file 1: of Subclinical and clinical atherosclerosis in rheumatoid arthritis: results from the 3-year, multicentre, prospective, observatio…

2019

STROBE 2007 (v4) checklist of items to be included in reports of observational studies in epidemiology* (DOC 96 kb)

Lo sviluppo sensomotorio del lattante

1999

International audience

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…

ABERRANT EXPRESSION OF IL-22RA1 ON HEMATOPOIETIC CELLS AS IMMUNOLOGICALLY SIGNATURE OF PRIMARY SJOGREN’S SYNDROME AND SJOGREN-ASSOCIATED NON-HODGKIN …

2013

Background: Interleukin (IL)-22 is a potent mediator of cellular inflammatory responses that has been recently reported to play a role in the pathogenesis of primary Sjogren's Syndrome (p-SS) (1, 2) and of T and B lymphomas. IL-22 biological activity is initiated by binding to a cell-surface complex composed of two subunits, IL-22R1 and IL-10R2 receptor chains, and further regulated by interactions with a soluble binding protein, IL-22BP. Unlike the IL-10R2, which is constitutively expressed in many human tissues, IL-22R1 is not detectable in immune cells. Objectives: Aim of this study was to better characterize the role of IL-22 axis in the pathogenesis of p-SS and p-SSassociated lymphomas…

Longterm Retention of Tumor Necrosis Factor-α Inhibitor Therapy in a Large Italian Cohort of Patients with Rheumatoid Arthritis from the GISEA Regist…

2012

Objective.To evaluate 4-year retention rates of tumor necrosis factor-α (TNF-α) inhibitors adalimumab, etanercept, and infliximab among patients with longstanding rheumatoid arthritis (RA), as derived from an Italian national registry.Methods.The clinical records of 853 adult patients with RA in the GISEA (Gruppo Italiano Studio Early Arthritis) registry were prospectively analyzed to compare drug survival rates and the baseline factors that may predict adherence to therapy.Results.In 2003 and 2004, 324 patients started treatment with adalimumab, 311 with etanercept, and 218 with infliximab. After 4 years, the global retention rate of anti-TNF-α therapy was 42%. Etanercept survival (51.4%) …

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…