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Objective: Since of the last publication of last recommendations on primary large-vessel vasculitis (LVV) endorsed by the Italian Society of Rheumatology (SIR) in 2012, new evidence emerged regarding the diagnosis and the treatment with conventional and biologic immunosuppressive drugs. The associated potential change of clinical care supported the need to update the original recommendations. Methods: Using the grading of recommendations assessment, development and evaluation (GRADE)-ADOLOPMENT framework, a systematic literature review was performed to update the evidence supporting the European Alliance of Associations for Rheumatology (EULAR) guidelines on LVV as reference. A multidisciplinary panel of 12 expert clinicians, a trained nurse, and a patients’ representative discussed the recommendation in cooperation with an Evidence Review Team. Sixty-one stakeholders were consulted to externally review and rate the recommendations. Results: Twelve recommendations were formulated. A suspected diagnosis of LVV should be confirmed by imaging or histology. In active GCA or TAK, the prompt commencement of high dose of oral glucocorticoids (40-60 mg prednisone-equivalent per day) is strongly recommended to induce clinical remission. In selected patients with GCA (e.g., refractory or relapsing disease or patients at risk of glucocorticoid related adverse effects) the use of an adjunctive therapy (tocilizumab or methotrexate) is recommended. In all patients diagnosed with TAK, adjunctive therapies, such as conventional synthetic or biological immunosuppressants, should be given in combination with glucocorticoids. Conclusions: The new set of SIR recommendations was formulated in order to provide a guidance on both diagnosis and treatment of patients suspected of or with a definite diagnosis of LVV.

Abstract Background Interstitial lung disease (ILD) is a severe systemic manifestation of rheumatoid arthritis (RA). High-resolution computed tomography (HRCT) represents the gold standard for the diagnosis of ILD, but its routine use for screening programs is not advisable because of both high cost and X-ray exposure. Velcro crackles at lung auscultation occur very early in the course of interstitial pneumonia, and their detection is an indication for HRCT. Recently, we developed an algorithm (VECTOR) to detect the presence of Velcro crackles in pulmonary sounds and showed good results in a small sample of RA patients. The aim of the present investigation was to validate the diagnostic accuracy of VECTOR in a larger population of RA patients, compared with that of the reference standard of HRCT, from a multicentre study. Methods To avoid X-ray exposure, we enrolled 137 consecutive RA patients who had recently undergone HRCT. Lung sounds of all patients were recorded in 4 pulmonary fields bilaterally with a commercial electronic stethoscope (ES); subsequently, all HRCT images were blindly evaluated by a radiologist, and audio data were analysed by means of VECTOR. Results Fifty-nine of 137 patients showed ILD (43.1%). VECTOR correctly classified 115/137 patients, showing a diagnostic accuracy of 83.9% and a sensitivity and specificity of 93.2 and 76.9%, respectively. Conclusions VECTOR may represent the first validated tool for the screening of RA patients who are suspected for ILD and who should be directed to HRCT for the diagnosis. Moreover, early identification of RA-ILD could contribute to the design of prospective studies aimed at elucidating unclear aspects of the disease.

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Objective: to provide evidence-based up-to-date recommendations for the management of patients with a definite diagnosis of polymyalgia rheumatica (PMR). Methods: A systematic literature review was performed to find the existing clinical practice guidelines (CPGs) on PMR and the framework of the Guidelines International Network Adaptation Working Group was used to appraise (AGREE II), synthesize, and customize the recommendations according to the needs of the Italian healthcare context. Rheumatologists on behalf of the Italian Society of Rheumatology (SIR) and from the SIR Epidemiology Unit joined the working group and identified the key health questions on PMR to guide the systematic literature review. Physicians, including general practitioners and specialists, and health professionals who manage PMR in the clinical practice were the target audience. The final recommendations were rated externally by a multi-disciplinary and multi-professional group of stakeholders. Results: From the systematic search in databases (Medline, Embase) and grey literature, 3 CPGs were identified and appraised by two independent raters. Combining the statements and the evidence from these CPGs, 9 recommendations were developed by endorsement or adaptation in response to the initial key health questions. The quality of evidence was graded and the working group discussed the final recommendations in view of their implementation in the Italian healthcare context. Conclusions: In absence of national guidelines so far, these recommendations are the first to provide guidance for the management of patients with a diagnosis of PMR in Italy and they are expected to ensure the best evidence-based clinical practice for this disease.

Gitelman syndrome (GS) is an inherited salt-wasting tubulopathy characterized by hypocalciuria, hypokalemia, hypomagnesemia and metabolic alkalosis, due to inactivating mutations in the SLC12A3 gene. Symptoms may be systemic, neurological, cardiovascular, ophthalmological or musculoskeletal. We describe a 70 year-old patient affected by recurrent arthralgias, hypoesthesia and hyposthenia in all 4 limbs and severe hypokalemia, complicated by atrial flutter. Moreover, our patient reported eating large amounts of licorice, and was treated with medium-high dosages of furosemide, thus making diagnosis very challenging. Genetic analysis demonstrated a novel heterozygous mutation in the SLC12A3 gene; therefore, we diagnosed GS and started potassium and magnesium replacement. GS combined with chondrocalcinosis and neurological involvement is quite common, but this is the first case of an EMG-proven severe neuropathy associated with GS. Herein, we underline the close correlation between hypomagnesemia, chondrocalcinosis and neurological involvement. Moreover, we report a new heterozygous mutation in exon 23 (2738G>A), supporting evidence of a large genetic heterogeneity in this late-onset congenital tubulopathy.

Polymyalgia rheumatica (PMR) is one of the most common rheumatic inflammatory disorders in people aged over 50. It is characterized by aching and prolonged morning stiffness in the shoulder and pelvic girdles and neck. To date there are no specific diagnostic tests, and in clinical practice the diagnosis of PMR remains based on its characteristic clinical manifestations, laboratory evidence of systemic inflammation, rapid response to low doses of glucocorticoids and exclusion of other disorders that may present with proximal pain and stiffness. For classification purposes, several criteria have been proposed over time based on retrospective clinical series, but none have been validated and received universal acceptance. Recently, an international collaborative initiative between the EULAR and the ACR was undertaken to develop new polymyalgia rheumatica classification criteria. In this review, the provisional 2012 EULAR/ACR classification criteria will be presented and their contribution for the diagnosis of polymyalgia rheumatica will be discussed.

Polymyalgia rheumatica (PMR) is a chronic, inflammatory disorder of unknown cause clinically characterized by pain and prolonged morning stiffness affecting the shoulders and often the pelvic girdle and neck. Imaging has substantially contributed to defining PMR as a disease mainly involving extra-articular structures. This review article analyses the role of the different imaging techniques in the diagnosis and follow-up of patients with PMR with particular emphasis on the role of ultrasound, PET/CT and MRI.

Psoriatic arthritis (PsA) is a chronic inflammatory disease involving skin, peripheral joints, entheses, and axial skeleton. The disease is frequently associated with extrarticular manifestations (EAMs) and comorbidities. In order to create a protocol for PsA diagnosis and global assessment of patients with an algorithm based on anamnestic, clinical, laboratory and imaging procedures, we established a DElphi study on a national scale, named Italian DElphi in psoriatic Arthritis (IDEA). After a literature search, a Delphi poll, involving 52 rheumatologists, was performed. On the basis of the literature search, 202 potential items were identified. The steering committee planned at least two Delphi rounds. In the first Delphi round, the experts judged each of the 202 items using a score ranging from 1 to 9 based on its increasing clinical relevance. The questions posed to experts were How relevant is this procedure/observation/sign/symptom for assessment of a psoriatic arthritis patient? Proposals of additional items, not included in the questionnaire, were also encouraged. The results of the poll were discussed by the Steering Committee, which evaluated the necessity for removing selected procedures or adding additional ones, according to criteria of clinical appropriateness and sustainability. A total of 43 recommended diagnosis and assessment procedures, recognized as items, were derived by combination of the Delphi survey and two National Expert Meetings, and grouped in different areas. Favourable opinion was reached in 100% of cases for several aspects covering the following areas: medical (familial and personal) history, physical evaluation, imaging tool, second level laboratory tests, disease activity measurement and extrarticular manifestations. After performing PsA diagnosis, identification of specific disease activity scores and clinimetric approaches were suggested for assessing the different clinical subsets. Further, results showed the need for investigation on the presence of several EAMs and risk factors. In the context of any area, a rank was assigned for each item by Expert Committee members, in order to create the logical sequence of the algorithm. The final list of recommended diagnosis and assessment procedures, by the Delphi survey and the two National Expert Meetings, was also reported as an algorithm. This study shows results obtained by the combination of a DElphi survey of a group of Italian rheumatologists and two National Expert Meetings, created with the aim of establishing a clinical procedure and algorithm for the diagnosis and the assessment of PsA patients. In order to find accurate and practical diagnostic and assessment items in clinical practice, we have focused our attention on evaluating the different PsA domains. Hence, we conceived the IDEA algorithm in order to address PsA diagnosis and assessment in the context of daily clinical practice. The IDEA algorithm might eventually lead to a multidimensional approach and could represent a useful and practical tool for addressing diagnosis and for assessing the disease appropriately. However, the elaborated algorithm needs to be further investigated in daily practice, for evidencing and proving its eventual efficacy in detecting and staging PsA and its heterogeneous spectrum appropriately.

A 57-year-old woman with a diagnosis of antisynthetase syndrome (ASSD) underwent a nailfold videocapillaroscopy (NVC) showing a scleroderma pattern. Alterations in capillary morphology have been reported in adults with inflammatory myositis (IM) but only recently have the differences in NVC findings between these two diseases been established. ASSD is currently classified as a subset of IM, for which reason only a few studies in literature evaluate its specific hallmarks, showing nonspecific features of NVC in patients with polymyositis and dermatomyositis (DM) and antisynthetase antibodies. To our knowledge, this is the first description of ASSD capillaroscopy features, and the first report of NVC in ASSD with evidence of scleroderma pattern. Further studies are needed to define clearly frequency, typical features, and possible correlation with clinical and serological data of NVC changes in ASSD, differences between microangiopathy in ASSD and systemic sclerosis or DM.

The objective of this study was to evaluate the predictive factors for achieving partial remission (PR) in patients with ankylosing spondylitis (AS) treated with anti-TNFα. We longitudinally enrolled in a multi-center study 214 AS patients, classified according to New York criteria, treated with anti-TNFα drugs adalimumab (ADA), etanercept (ETA) and infliximab (INF) with at least 12 months of follow up. PR was reached when the score was

BACKGROUND Interleukin-6 (IL-6) is a polyfunctional cytokine that regulates a very large number of cellular activities. Its implication in acute-phase reactant production by hepatocytes is of particular interest, as is its involvement in chronic inflammatory diseases, mainly rheumatoid arthritis, Crohn’s disease, and Castleman’s disease. Transgenic mice lacking IL-6 expression were completely protected against collagen-induced arthritis, and Tumor Necrosis Factor (TNF-alpha) induces synovial cells to produce IL-6 and their proliferation. However, there is still some controversies regarding the unique proinflammatory activity of IL-6. Some studies have demonstrated that IL-6 and TNF-alpha may have an opposite effect in synovial cultured cells since IL-6 could represent a negative loop for TNF-alpha induced synovitis. However, phase III studies of rheumatoid arthritis patients treated with anti IL-6 receptor (tocilizumab) indicate an acceptable safety profile relative to the clinical benefit. AIM OF THE STUDY In this review, we summarized the rationale and the main evidence regarding the therapeutic benefit of blocking IL-6 activity in rheumatoid arthritis.

Epidemiological studies on psoriatic arthritis have long been hampered by the absence of widely accepted classification criteria. The development of the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria has recently provided the framework for conducting epidemiological studies in psoriatic arthritis using uniform recruitment criteria. However, so far, only a minority of studies have adopted such criteria. In addition to the lack of shared classification criteria, differences in study settings, designs, and ascertainment methods have contributed to yield substantial disparities in the estimates of the incidence (from 3,02 to 23,1 cases per 100,000 people) and prevalence (from 49,1 to 420 cases per 100,000 people) of psoriatic arthritis around the globe. Overall, the available data suggests that the prevalence of psoriasis in the general population is approximately 2-3%, with about a third of patients with psoriasis having arthritis. Therefore, psoriatic arthritis may affect 0,3- 1,0% of the population, a frequency not dissimilar from that of rheumatoid arthritis. Future epidemiological studies should be carried out in larger numbers of patients diagnosed using consistent criteria.

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Disease activity assessment in large vessel vasculitis (LVV) is often challenging for physicians. In this study, we compared the assessment of disease activity based on inflammatory markers, clinical indices (Indian Takayasu Activity Score [ITAS] and the Kerr/National Institute of Health indices [Kerr/NIH]), and 18F-Fluorodesossiglucose (FGD) vascular uptake at positron emission tomography (Pet). We found that Pet results did not statistically correlate with the clinical indices ITAS and Kerr/NIH, because FDG uptake was increased (grade>2 on a 0-3 scale in at least one evaluated vascular segment) in many patients with inactive disease according to clinical and laboratory parameters (i.e., negative ITAS and Kerr/NIH indices as well as normal erythrocyte sedimentation rate (ESR) and C-reactive protein (PCR)). Similarly, interleukin- 6 and its soluble receptor did not statistically correlate with disease activity. In contrast, clinical indices showed a significant correlation between each other and with inflammatory markers (VES and PCR). These data suggest that while clinical indices and inflammatory markers may be useful to assess disease activity, Pet may be more sensitive.

Due to the heterogenous clinical picture, with a possible combination in any individual patient of axial disease, peripheral arthritis, enthesitis and dactylitis, psoriatic arthritis (PsA) is difficult to assess. Validated assessment tools for PsA are lacking. Recently, international study groups have a special interest in developing and validating standardized tools to assess PsA. We will review the existing assessment modalities of PsA focusing on axial diasese, peripheral arthritis, enthesitis and dactylitis. Measures of function and disability recommended for PsA will be also reviewed. Key words: Psoriatic arthritis, assessment tools, clinical trials

L’artrite psoriasica (AP) è sempre stata considerata una malattia più lieve dell’artrite reumatoide (AR) e ad evoluzione non invalidante. Studi recenti hanno invece dimostrato che circa il 40% dei pazienti ha una malattia erosiva con sviluppo di deformità (1, 2). Similmente all’AR, una terapia aggressiva con uno o più farmaci di fondo nelle fasi iniziali potrebbe ostacolare la progressione del danno articolare. Inoltre, diversamente dall’AR, la AP può interessare anche lo scheletro assiale dove può dare limitazione funzionale e deformità simili a quelle della spondilite anchilosante (SA). Il trattamento iniziale dell’AP prevede l’uso dei farmaci anti-infiammatori nonsteroidei (FANS) e delle infiltrazioni locali di steroidi. I farmaci di fondo sono riservati alle forme resistenti e destruenti. Methotrexate (MTX), sulfasalazina (SSZ) e ciclosporina (CsA) sono i farmaci di fondo più frequentemente utilizzati, anche se non vi sono studi controllati che abbiano dimostrato la loro capacità di bloccare l’evoluzione erosiva dell’artrite periferica (3-8). Per quanto riguarda l’interessamento assiale tali farmaci non sono in grado di controllare i sintomi quali dolore e rigidità mattutina (5). Recentemente una nuova classe di farmaci, in grado di bloccare il tumor necrosis factor TNF (anti- TNF), si è dimostrata efficace nel rallentare l’evolutività erosiva nella AR e nel controllare i sintomi della SA (9, 10)...

La spondilite anchilosante è la malattia più rappresentativa del gruppo delle spondiloartriti. Di esso fanno parte anche l’artrite reattiva, l’artrite psoriasica, l’artrite associata alla colite ulcerosa ed alla malattia di Crohn e forme che non rientrando in nessuna della categorie precedenti sono dette indifferenziate (1). Si tratta di malattie molto frequenti che complessivamente colpiscono l-2% della popolazione (2). La spondilite anchilosante inizia di solito nella seconda e terza decade di vita ed è più frequente nel sesso maschile. In molti casi la malattia è progressiva ed è causa di un grado di disabilità non inferiore a quello provocato dall’artrite reumatoide (3). Gli scopi della terapia della spondilite anchilosante sono: ridurre l’intensità del dolore e della rigidità, migliorare la funzione, contrastare la progressione del danno radiologico e prevenire la disabilità. Sino a poco tempo fa la terapia della spondilite anchilosante consisteva nella somministrazione di farmaci antinfiammatori non-steroidei (FANS) e nel programma di riabilitazione. I FANS sono efficaci nel controllo del dolore e della rigidità e consentono anche di ottenere un miglioramento della funzione.

Reactive Arthritis (ReA) is an aseptic synovitis developing after a primary infection distant from the joint, mainly localized in the gastrointestinal (Enteroarthritis) or genitourinary tract (Uroarthritis). Because of either the asymmetric joint involvement, the possibility of involvement of the spine and enthesis, and the HLA-B27 association ReA is considered one of the spondylarthropathies. Recently, bacterial components or viable bacteria were found in joints during ReA. For this reason, the limits between ReA itself and infectious arthritis are now less definite. Generally accepted diagnostic and classification criteria are still lacking but the improvement in techniques for detection of bacteria increase the possibility to identify the triggering agents. Several studies have examined the role of antimicrobial drugs in ameliorating the natural course of ReA, with some positive results for Uroarthritis only. However, more conventional treatments based on NSAIDs, Sulfasalazine and steroids are effective in many cases.

Objective. To evaluate the impact of traditional cardiovascular risk factors, carotid atherosclerosis and the effect of anti-platelet/anti-coagulant therapy on the occurrence of severe cranial ischaemic events (CIEs) in GCA. Methods. We identified 180 Reggio Emilia (Italy) residents with biopsy-proven GCA diagnosed between 1986 and 2005. We evaluated data on demographics, clinical features, laboratory investigations, cardiovascular risk factors, anti-platelet/anti-coagulant use and carotid atherosclerosis. Results. Systemic signs/symptoms were significantly less frequent (P = 0.004) and ESR and C-reactive protein (CRP) values at diagnosis were significantly lower (P = 0.03 and P = 0.04, respectively) in patients with CIEs. The prevalence of hypertension and ischaemic heart disease was significantly higher in patients with CIEs than in those without (P = 0.01 and P = 0.006, respectively). Patients treated with anti-platelet/anti-coagulant therapy were significantly more likely to suffer CIEs than those without (P = 0.03), while CIEs were significantly associated with ischaemic heart disease in this subset of patients (P = 0.02). By multivariate logistic regression, we found that the best predictors for the development of severe CIEs included the absence of high (>5.38 mg/dl) CRP levels at diagnosis (OR = 0.31, 95% CI 0.08, 1.20), the absence of systemic manifestations (OR = 0.30, 95% CI 0.08, 1.08), the presence of hypertension (OR = 7.77, 95% CI 0.83, 72.76), and a past history of ischaemic heart disease (OR = 8.65, 95% CI 0.92, 80.95). Conclusions. In GCA, hypertension, a past history of ischaemic heart disease and a low inflammatory response are associated with a higher risk of developing severe CIEs. [ABSTRACT FROM AUTHOR]

Objectives. To describe the clinical features and outcomes of patients with primary central nervous system vasculitis (PCNSV) and cerebral amyloid angiopathy (CAA) from a large cohort of consecutive patients with PCNSV treated at a single institution. Methods. We identified 101 consecutive patients with PCNSV admitted between January 1983 and December 2003. PCNSV diagnoses were based on findings from a central nervous system (CNS) biopsy (n = 31) and conventional angiography (n = 70). CNS tissue specimens from 49 cases were examined histologically, and 49 were stained for amyloid deposits. Those with vascular amyloid deposits (CAA) were compared with those without histological evidence of amyloid deposition. Results. Eight cases (26%) with CNS biopsy specimens positive for PCNSV also showed findings of CAA. Compared with patients with PCNSV only, these patients were older at diagnosis, predominantly male, had a more acute onset, a higher frequency of cognitive dysfunction and showed prominent gadolinium-enhanced leptomeningeal lesions with MRI. Histologically, all had a granulomatous vascular inflammatory pattern. Six patients responded promptly to therapy. Outcomes at last follow-up were similar in the two groups. Conclusions. PCNSV with CAA appears to form a clinical subset of PCNSV. The vasculitis influences the clinical findings to a greater degree than the presence of amyloid deposits in the vessels. [ABSTRACT FROM AUTHOR]

Objective. To evaluate costs, benefits and cost–effectiveness of anti-TNF agents in PsA patients with inadequate response to conventional treatment. Methods. A total of 107 patients, from nine Italian rheumatology centres, with different forms of PsA were given anti-TNF treatment, mainly etanercept (87%). Information on resource use, health-related quality of life, disease activity, function and laboratory values were collected at baseline and through out the 12 months of therapy. Cost (expressed in euro 2007) and utility (measured by EuroQol) before and after anti-TNF therapy initiation were compared in order to estimate the incremental cost per quality-adjusted life year (QALY) gained, and cost–effectiveness acceptability curve was calculated. Results. At the end of 12 months, there was a significant increase in direct cost due to an increase of drug cost caused by TNF inhibitors that was only partially offset by the decrease in indirect cost. In the last 6 months of therapy, the direct cost increased by €5052, the cost for the National Health System (NHS) by €5044 and the social cost by €4638. However, a gain of 0.12 QALY resulted in a cost per QALY gained of €40 876 for the NHS and of €37 591 for the society. The acceptability curve showed that there would be a 97% likelihood that anti-TNF therapy would be considered cost-effective at willingness-to-pay threshold of €60 000 per QALY gained. Conclusion. Cost–effectiveness ratios are within the commonly accepted willingness-to-pay threshold. These results need to be confirmed in larger samples of patients. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the frequency and duration of clinical remission in patients with PsA. Methods. All consecutive new outpatients with peripheral PsA requiring second-line drugs and RA observed between January 2000 and December 2005 were included in a prospective, case-control study. Primary end point was to assess the frequency of remission in peripheral PsA compared with RA. Secondary end points were to compare the duration of clinical remission during treatment and after therapy interruption, ACR 20, 50, 70 response rates and to detect any remission predictor at diagnosis. Treatment regimen was standardized in both groups. From January 2003 to December 2005, therapy was suspended in PsA patients and controls if achieving remission. Results. One or more episodes of remission occurred in 57/236 (24.1%) PsA patients and in 20/268 (7.5%) controls (P < 0.001). The mean duration of remission was of 13 ± 9.4 months in PsA patients and 4 ± 3.7 in controls (P > 0.001). Remission episodes were more frequent in PsA patients treated with anti-TNF compared with those receiving traditional DMARDs (P > 0.001), with no differences regarding the duration. After therapy interruption, the remission duration was 12 ± 2.4 months in PsA and 3 ± 1.5 in RA (P < 0.001). No remission predictor at diagnosis resulted by multivariate analysis. Conclusion. Remission is possible in up to 24% of patients with peripheral PsA. It is significantly more frequent, but not longer, in patients receiving anti-TNF drugs compared with those treated with traditional DMARDs. Patients remain in remission for a long period after therapy interruption, thus suggesting an intermittent therapeutic strategy. [ABSTRACT FROM AUTHOR]

Imaging studies play a central role in diagnosing and monitoring giant-cell and Takayasu arteritis. Deep, large vessels can be examined by CT or MRI, while colour Doppler ultrasound and MRI have been used with promising results to investigate the temporal arteries. Positron emission tomography is very sensitive in detecting large-vessel inflammation, although it does not delineate the vessel wall. Imaging procedures can also be used to monitor the disease course. However, imaging signs of inflammation may sometimes persist despite clinical remission and, conversely, seemingly unaffected vessels may develop alterations later on. [ABSTRACT FROM AUTHOR]

Objective. To investigate potential associations between the −463 G/A myeloperoxidase (MPO) promoter polymorphism and susceptibility to, and clinical expression of, Behçets disease (BD). Methods. One hundred and seventy-five Italian patients who satisfied the International Study Group criteria for BD and 235 healthy age- and sex-matched blood donors were genotyped for the −463 G/A promoter polymorphism of the MPO gene by molecular methods. The patients were subgrouped according to the presence or absence of clinical manifestations. Results. The distribution of allele and genotype frequencies of the MPO −463A/G polymorphism did not differ significantly between the BD patients and the healthy controls. Carriers of the −463 A allele (A/A or A/G) [odds ratio (OR) 0.7, 95% confidence interval (CI) 0.5–1.1] and homozygosity for A allele (OR 0.3, 95% CI 0.1–1.3) were less frequent among BD patients than among the controls, but the difference was not statistically significant. No significant associations were found when BD patients with and those without clinical manifestations were compared. Conclusion. Our data suggest that the −463 G/A promoter polymorphism of the MPO gene is not associated with susceptibility to, and clinical expression of, BD in Italian patients. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the effects of angiotensin II (Ang II) treatment on apoptosis of fibroblast-like synoviocytes (FLS) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Methods. AT1 receptor expression was detected by western blotting and flow cytometry. Apoptosis induction was quantified by nucleosome ELISA and by TUNEL; cell proliferation was determined by a bromodeoxyuridine (BrdU) incorporation assay. Silencing of p65 NF-κB was obtained by using a specific siRNA. Caspase 3 activation was evaluated by a colorimetric assay and its cleavage by western blotting. Results. AT1 expression resulted comparable in FLS from OA and RA patients. Ang II pre-treatment reduced FLS apoptotic response to serum starvation and nitric oxide (NO) exposure. This protective effect was reverted in the presence of the AT1 receptor antagonist losartan as well as after silencing the expression of NF-κB. Moreover, FLS treatment with the caspase inhibitor z-VAD-fmk cancelled this Ang II effect on apoptosis. Caspase 3 activation was reduced in presence of Ang II. Conclusions. Ang II could represent an important mediator involved in FLS expansion, reducing their capacity to undergo apoptosis, through the activation of NF-κB and the blockage of caspase cascade. [ABSTRACT FROM AUTHOR]