1,721,093 research outputs found
L’interpretazione degli eventi neuropsichiatrici in corso di LES: un problema di attribuzione
No full textPresentazione di un algoritmo diagnostico per l'attribuzione degli eventi neuropsichiatrici in corso di LE
PHARMACOLOGICAL ROLE OF A2A ADENOSINE RECEPTORS IN SYSTEMIC LUPUS ERYTHEMATOSUS, CLINICAL AND LABORATORY CORRELATIONS
No full textIl Lupus Eritematoso Sistemico (LES) è il prototipo dei disordini autoimmuni sistemici caratterizzato da un ampio di presentazioni cliniche a carico di organi e tessuti. La rottura irreversibile dei meccanismi implicati nella risposta immunologica si manifesta con risposte autoimmuni nei confronti di antigeni nucleari endogeni e con la formazione di autoanticorpi e immunocomplessi (IC). Il LES è stato classicamente considerato una malattia autoimmune in cui il sistema immunitario adattativo gioca un ruolo predominante attraverso le cellule T e B fortemente implicate nel processo patogenetico. Durante la fase infiammatoria precoce le cellule dendritiche (CD) sono in grado di interiorizzare acidi nucleici contenenti complessi immunitari che raggiungono gli endosomi e stimolano il recettore Toll-like (TLR) 7 o 9 alla trascrizione genica di interferon (IFN)-α. IFN-α contribuisce alla maturazione delle CD mieloidi che possono attivare le cellule T autoreattive attraverso la presentazione dell'antigene e la costimolazione. Questo favorisce lo sviluppo di cellule T helper responsabili della produzione di citochine proinfiammatorie e stimola la maturazione e la differenziazione delle cellule B, la produzione di anticorpi, e la formazione di IC. Nel LES, inoltre, i monociti secernenti IC e IFN-α modulano attivamente la funzione di interleuchina (IL)-10. Nella malattia, peraltro, la capacità di IL-10 di sopprimere la produzione di citochine infiammatorie come fattore di necrosi tumorale (TNF)-α e interleuchina IL-6 è ridotta. Sempre maggiori evidenze sottolineano come l'adenosina svolga un ruolo attivo di regolazione locale di infiammazione in diverse patologie. L'adenosina è un nucleoside onnipresente coinvolto in varie funzioni fisiologiche e patologiche, attraverso lo stimolo dei recettori dell’adenosina (RA) A1, A2A, A2B, e A3 accoppiati a proteine G. Il ruolo dei RA è ben noto in condizioni fisiologiche e in una varietà di patologie, compresa l’infiammazione, le malattie neurodegenerative e il cancro. In particolare, la stimolazione A2AAR media l’inibizione di TNF-α, IL-1β, IL-2, IL-6, IFN-α e aumenta la produzione della citochina antinfiammatoria IL-10. Da questo background è maturato l’obiettivo dello studio di verificare l'ipotesi che un’alterazione dei recettori A1, A2A, A2B, e A3 dell'adenosina nei linfociti di pazienti con LES possa essere implicata nella patogenesi della malattia e di esaminare le correlazioni tra lo stato recettoriale ed i parametri clinici dei pazienti lupici. Metodi: I RA sono stati analizzati mediante saggi di saturazione di legame, analisi dell’mRNA e Western blotting nei linfociti di pazienti con LES, seguiti regolarmente presso
la nostra clinica dedicata al Lupus e accuratamente caratterizzati, e confrontati con soggetti sani. E’ stato inoltre testato l'effetto dell’agonista A2AARs sulla via regolata dal fattore nucleare kB (NF-kB) e sul rilascio di IFN-α, sul TNF-α, interleuchina IL-2, IL-6, IL-1β e IL-10. Risultati: nei linfociti ottenuti da 80 pazienti affetti da LES i recettori RAA2A sono risultati up-regolate se confrontati con 80 controlli sani appaiati per sesso ed età, mentre A1, A2B e A3 sono rimasti invariati. La densità de RAA2A è risultata inversamente correlata con l'attività della malattia misurata attraverso lo SLEDAI index-2000 (SLE disease activity index-2000), l'attività della malattia valutata nel tempo secondo precisi modelli di decorso clinico, sierosite, ipocomplementemia e presenza di anti-dsDNA. L’attivazione dei RAA2A ha inibito la via regolata dall’NF-kB e il rilascio di citochine infiammatorie (IFN-alfa, TNFalfa, IL-2, IL-6, IL-1β), mentre ha potenziato il rilascio della citochina anti-infiammatoria IL10. Conclusione: Questi dati suggeriscono il coinvolgimento dei RAA2A nella complessa rete patogenetica del LES, agendo come un sistema di modulazione del processo infiammatorio. Questo potrebbe rappresentare un percorso di compensazione per contrastare meglio l'attività della malattia. Infatti, l'attivazione dei RAA2A riduce significativamente il rilascio di citochine pro-infiammatorie e amplifica quelle con attività anti-infiammatoria suggerendo un potenziale uso traslazionale di agonisti RAA2A nel trattamento farmacologico del LES.Systemic lupus erythematosus (SLE) is the prototypic multisystem autoimmune disorder with a broad spectrum of clinical presentations encompassing almost all organs and tissues. The irreversible break in immunological tolerance is manifested by immune responses against endogenous nuclear antigens and the subsequent formation of autoantibodies and immune complexes. SLE has classically been considered an autoimmune disease with a predominant adaptive immune system component, since T and B cells have been considered the most important pathogenetic players. During the early inflammatory phase plasmacytoid dendritic cells (pDCs) are able to internalize nucleic acids containing interferogenic immune complexes (ICs) that reach the endosomes and stimulate Toll-like receptors (TLR) 7 or 9, leading to interferon (IFN)-α gene transcription. IFN-α contributes to the maturation of myeloid DCs that can activate autoreactive T cells through antigen presentation and costimulation. This favours the development of T helper 1 cells responsible for high-level production of proinflammatory cytokines and enhance B cell maturation and differentiation, antibody production, and immune complex formation. In SLE the IC and IFN-α secreting monocytes modulate interleukin (IL)-10 function. The capability of IL-10 to suppress production of inflammatory cytokines such as tumour necrosis factor (TNF)-α and IL-6, implicated in promoting autoimmunity and tissue inflammation in SLE, is attenuated. Growing evidence emphasizes that the purine nucleoside adenosine plays an active role as a local regulator of inflammation in different pathologies. Adenosine is an ubiquitous nucleoside involved in various physiological and pathological functions by stimulating the G protein-coupled A1, A2A, A2B and A3 adenosine receptors (ARs). The role of ARs is well known in physiological conditions and in a variety of pathologies including inflammatory damage, neurodegenerative disorders and cancer. In particular, A2AAR stimulation mediates inhibition of TNF-α, IL-1β, IL-2, IL-6, IFN-α and increases the production of the anti-inflammatory cytokine IL-10. Objective: To test the hypothesis that dysregulation of A1, A2A, A2B, and A3 adenosine receptors (ARs) in lymphocytes from patients with Systemic Lupus Erythematosus (SLE) may be involved in the pathogenesis of the disease and to examine the correlations between the status of the ARs and the clinical parameters of SLE patients. Methods: ARs were analysed by saturation binding assays, mRNA and Western blotting analysis in lymphocytes from SLE patients regularly attending the Lupus clinic and
faithfully characterized and compared with healthy subjects. The effect of A2AAR agonist in nuclear factor kB (NF-kB) pathway and on the release of IFN-α, TNF-α, IL-2, IL-6, IL-1β and IL-10 were tested. Results: In lymphocytes obtained from 80 SLE patients A2AARs were up-regulated if compared with 80 age-matched healthy controls while A1, A2B and A3 ARs were unchanged. A2AAR density was inversely correlated with SLE disease activity index-2000, disease activity over time evaluated accordingly to the course patterns, serositis, hypocomplementemia and anti-dsDNA positivity. A2AAR activation inhibited the NF-kB activation pathway, diminished inflammatory cytokines (IFN-α, TNF-α, IL-2, IL-6, IL-1β) but potentiated the release of anti-inflammatory IL-10. Conclusion: These data suggest the involvement of A2AARs in the complex pathogenetic network of SLE, acting as a modulatory system of the inflammatory process. It could represent a compensatory pathway to better counteract the disease activity. The A2AAR activation significantly reduces the release of pro-inflammatory cytokines while enhancing those with anti-inflammatory activity suggesting a potential translational use of A2AAR agonists in SLE pharmacological treatment
Editorial: Autoimmune and inflammatory rheumatic diseases: Identifying biomarkers of response to therapy with biologics: Volume II
Full text linkNo abstract available
Overlap fra neuro-LES e sindromi demielinizzanti
No full textRassegna sugli aspetti di diagnosi differenziale tra sclerosi multipla e LES neuropsichiatric
Osteoarthritis and its management - Epidemiology, nutritional aspects and environmental factors
No full textOsteoarthritis (OA) is the most prevalent chronic rheumatic diseases worldwide, with a strong impact on individual and population health. OA is a clinically heterogeneous disease presenting with different clinical phenotypes recognising systemic and local risk factors. The pathogenesis is multifactorial including constitutive features of the joint, non-modifiable and modifiable risk factors. Epidemiological studies highlight the link between metabolic syndrome and OA and the effect of interplay between immunological and metabolic processes is getting increasing emphasis because of to the discovery that metabolic syndrome is implicated in OA pathogenesis and progression. In addition, recent findings suggest a potential role of dietary factors in susceptibility and progression of OA. In this review, we summarise the most robust evidence on epidemiology and classical risk factors OA, also exploring the most recent evidence on metabolic changes and Mediterranean diet for OA as a possible target to impact on the natural history of the disease
Lupus or not lupus? Neuropsychiatric symptom attribution in systemic lupus erythematosus
No full textEditoriale sul tema dell'attribuzione degli eventi neuropsichiatrici in corso di LE
Impact of rheumatoid arthritis and methotrexate on pregnancy outcomes: retrospective cohort study of the Italian Society for Rheumatology
No full textOBJECTIVE: To evaluate the impact of rheumatoid arthritis (RA) and methotrexate (MTX) on the probability of becoming pregnant, pregnancy losses, elective termination of pregnancy (TOP) and congenital malformations. METHODS: A retrospective cohort study on administrative healthcare databases was conducted. Three patients’ cohorts were enrolled among childbearing-age women. The first cohort included patients with RA starting MTX between July 2004 and December 2011. The second cohort included patients with RA without MTX treatment randomly selected from the same population (ratio 1:1). Finally, a cohort of subjects without RA was identified (ratio 1:4). Multivariate logistic regression models were implemented, ORs and 95% CI were reported. RESULTS: The two matched RA cohorts included 3564 patients with MTX and without MTX. The cohort without RA included 14 256 subjects. In the three cohorts, the proportion of women achieving pregnancy during follow-up was 6.3%, 9.1% and 11.9%, respectively. Congenital malformations were very rare in all cohorts. RA women treated with MTX at any time before conception showed significantly higher risks of pregnancy losses than non-RA women (OR (95% CI) 2.22 (1.40 to 3.45)). We observed a significant positive relationship between the exposure to MTX in the 3 months window before conception and increased risk of elective TOP (OR (95% CI) 4.77 (1.08 to 19.40)). CONCLUSION: MTX-treated patients appeared to be the cohort with the highest risk of pregnancy losses. The positive association with elective TOP and exposure to MTX in the three months window before conception in patients with RA reinforces the need for adequate preconception counselling to avoid unplanned pregnancies
Application of SLICC classification criteria in undifferentiated connective tissue disease and evolution in systemic lupus erythematosus: Analysis of a large monocentric cohort with a long-term follow-up
No full textObjectives The objectives of this study were to analyse the performance of the Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria for systemic lupus erythematosus (SLE) in a large cohort of undifferentiated connective tissue disease (UCTD) population at onset of the disease and during a long-term follow-up of 15 years (1999-2013) and to evaluate the transition from UCTD to SLE, according to American College of Rheumatology (ACR) 1997 and SLICC 2012 classification criteria. Methods A cohort of patients who met the classification criteria proposed by Mosca et al. for UCTD, were analysed. The SLICC 2012 classification criteria for SLE were retrospectively applied to each patient at the time of the diagnosis (T0) and also periodically re-applied and compared to ACR 1997 criteria at three different time points in the follow-up. Results 329 patients were enrolled. According to inclusion criteria at T0 no patient met the SLE/ACR criteria, whilst, retrospectively applying the SLE/SLICC criteria, 44 patients already satisfied this set of criteria for SLE. During the follow-up 23 new patients reached the SLE/SLICC criteria and 14 patients met the ACR criteria with a stable rate of progression to SLE over time. Acute or subacute skin rash, antiphospholipid antibody (aPL) positivity and serositis were the variables correlated to the evolution to SLE. Conclusions In our UCTD population, the application of SLICC classification criteria for SLE at disease onset allowed identification of a proportion of otherwise missed SLE cases; during follow-up, and compared with ACR criteria, SLICC criteria expanded the number of patients classifiable as SLE otherwise classified as UCTD
Peripheral nervous system involvement in systemic lupus erythematosus: a review of the evidence
No full textIn the past years the peripheral nervous system (PNS) involvement in systemic lupus erythematosus (SLE) has received little attention despite its potential significant impact. The true prevalence of PNS in SLE reported in studies is variable and strongly influenced by American College of Rheumatology (ACR) case definition that includes seven PNS manifestations (acute inflammatory demyelinating polyradiculoneuropathy, autonomic disorder, mononeuropathy, myasthenia gravis, cranial neuropathy, plexopathy and polyneuropathy). Other peripheral manifestations, such as chronic inflammatory demyelinating polyradiculoneuropathy and small fibre neuropathy, not included in the ACR nomenclature, have not been well characterised in SLE. The aim of this review is to focus on epidemiology, pathogenesis, diagnosis and clinical features of all possible different expressions of PNS involvement in SLE, with the final objective to profile the patient's clinical characteristics
Epidemiology of gout and chondrocalcinosis
No full textGout is the most common cause of inflammatory arthritis affecting at least 1% of the population in industrialized countries. It is closely associated with hyperuricemia and is characterized by formation and reversible deposition of monosodium urate crystals in joints and extra-articular tissues. Several studies suggest that the prevalence and incidence of gout are rising. Numerous risk factors may in part explain this increasing trend including dietary and lifestyle changes, genetic factors, diuretic use and comorbid conditions such as hypertension, diabetes, cardiovascular disease, chronic renal disease and the metabolic syndrome. Chondrocalcinosis is characterized by the deposition of calcium pyrophosphate crystals in articular tissues, most commonly fibrocartilage and hyaline cartilage. Sporadic chondrocalcinosis is a common condition in the elderly and frequently associates with osteoarthritis. Hereditary haemochromatosis, hyperparathyroidism and hypomagnesaemia are metabolic disorders that predispose to secondary chondrocalcinosis.The prevalence of chondrocalcinosis is still rather uncertain and varies depending on the diagnostic criterion used in different studies
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