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Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the polyclonal activation of B lymphocytes and the production of autoantibodies that cause immune complex-related inflammation. Immunological factors derived from platelets modulate B cell function in SLE disease. However, platelets do not only modify the immune system by soluble factors. The binding of platelets to lymphocytes can modulate immune response. Thus, we speculate that the binding of platelets to lymphocytes in SLE patients may play a role in abnormal B lymphocyte response and the pathogenesis of SLE. We observed that levels of lymphocytes with bound platelets were higher in SLE patients than in healthy donors (HD). In SLE patients, the percentage of B lymphocytes with bound platelets positively correlated with plasmatic levels of IgG, IgA, IL-10, and soluble CD40L and negatively correlated with IgM levels, though not in HD. Preswitched memory B lymphocytes were the subpopulation with more bound platelets. Lymphocytes with bound platelets from both HD and SLE patients had major levels of CD86 and BAFFR and a greater production of IL-10 than lymphocytes without bound platelets. However, only B lymphocytes with bound platelets from SLE patients had increased levels of IgG and IgA on their surface. SLE patients with a suggestive renal manifestation had the highest levels of B and T lymphocytes with bound platelets. These results suggest that the binding of platelets to lymphocytes plays a role in SLE disease and that controlling this binding may be a promising therapeutic approach.

Blocking IL-6 pathways with sarilumab, a fully human anti-IL-6R antagonist may potentially curb the inflammatory storm of SARS-CoV2. In the present emergency scenario, we used "off-label"" sarilumab in 5 elderly patients in life-threatening condition not candidates to further active measures. We suggest that sarilumab can modulate severe COVID-19-associated Cytokine Release Syndrome."

Dear Editor, We read with interest the recent article by Singh and Cleveland on the hypersensitivity risk of allopurinol (ALP) and febuxostat (FBX) compared with colchicine.1 A common challenge when using ALP, linked to hypersensitivity reactions, is the potential development of cutaneous adverse reactions (CARs). Most are often mild, non-specific rashes; however, severe CARs, including Stevens-Johnson syndrome (SJS), may occur, but with a low incidence (0.69 cases per 1000 person-years) in non-Asian populations.2 In the EuroSCARs study, ALP was the reason for 5% of all severe CARs.3 So, FBX is often chosen as urate-lowering agent on the background of an ALP-related CAR. However, these patients were not eligible for the pivotal trials of FBX4 and were excluded from the recent analysis by Singh and Cleveland.1 Therefore, the accurate rate of FBX-related CARs in patients who previously suffered from ALP, and the mechanisms behind, remain undetermined to date. We have …

The aim of this study was to assess changes in the estimated glomerular filtration rate (eGFR) in gouty patients with chronic kidney disease (CKD) using a "treat-to-target" (T2T) approach in gout. This multicenter observational retrospective study included patients diagnosed with gout and CKD stage 3 taking xanthine oxidase inhibitors (XOIs) (allopurinol or febuxostat) for at least 12 months. All patients were treated using a T2T strategy according to national gout guidelines to achieve the target levels of serum uric acid (sUA; < 5-6 mg/dl) within 6 months of the first visit. The primary outcome was to assess changes in eGFR. The effects of independent variables were analyzed over eGFR in a linear mixed-effects (LME) model. Fifty patients with gout and CKD stage 3 treated with XOIs with a T2T strategy for 12 months were included. Eighty-two percent of the patients achieved the sUA target during the study period. The improvement seen in eGFR was higher during the first 6 months, showing a median increase of 7.54 ml/min/m(2) (SE = 1.25) and trending towards stability over 12 months. For every 1 mg/dl of decrease in sUA, an improvement of 1.5 ml/min/m(2) in eGFR was observed (coefficient +/- SE: - 1.58 +/- 0.26) (p < 0.001) with no differences between type and dosage of XOIs treatment, colchicine administration, age, sex, and smoking status. A reduction in sUA levels using a T2T approach with XOIs at an optimal dose is possible and could help conserve and improve renal function in gouty patients with CKD stage 3.

IL-6 contributes significantly to the chronic inflammatory process of rheumatoid arthritis (RA). Tocilizumab, a humanized anti-human IL-6 receptor antibody that blocks the signaling originated by the IL-6/IL-6R complex, is an effective treatment. However, predictors of the response to tocilizumab are still required. We aimed to combine IL-6 and soluble IL-6R (sIL-6R) levels to identify groups of responses.Heparinized blood and clinical data from 63 RA patients were collected before treatment and after 3 and 6 months. Two-step clustering (SPSS v.18) was used to establish the relationship between IL-6 and sIL-6R. Then, we compared European League Against Rheumatism (EULAR) response criteria with remission achievement in the groups of patients.Three statistical significant clusters of RA patients (i.e., g1, g2, and g3) were defined by serum concentrations of IL-6 and sIL-6R at baseline. All groups of RA patients had higher IL-6 and sIL-6R levels than healthy donors. The levels of IL-6 expressed as median (IQR) in g1 patients were 124(90-183)pg/ml, in g2 12.3(4.4-24)pg/ml, and in g3 60.1(30-146)pg/ml (p0.001). The levels of sIL-6R expressed as mean ± sd in g1 patients were 250.5 ± 72ng/ml, in g2 269.1 ± 125ng/ml, and in g3 732.7 ± 243ng/ml (p0.001). Disease activity score (DAS)28, C-reactive protein, and erythrocyte sedimentation rate were comparable in the three groups at baseline. Disease duration in g3 was the longest (median(IQR) years: g1 = 11(5-15), g2 = 12(8-20), and g3 23(16-26); p = 0.006), with years of disease evolution being correlated with sIL-6R levels (R = 0.417, p0.001). Simple and Clinical Disease Activity Index (SDAI and CDAI) decreased significantly in the three groups. However, EULAR response criteria and remission achievement at 6m was different in the three groups (p = 0.03 and 0.04, respectively). In all. 17 out of the 18 patients in g1 had a good or moderate response to tocilizumab. Conversely, the percentage of patients with no response to tocilizumab was higher in g3 than in g1 and g2. We also observed different changing patterns of IL-6 and sIL-6R levels among the three groups.RA patients could be easily stratified prior to therapeutic intervention with two molecules related to the pathway blocked by tocilizumab. G1 patients, who had the best response to tocilizumab, had the highest level of IL-6 and the lowest level of sIL-6R.

Background:Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease of unknown etiology. Tocilizumab (TCZ) is a first-line biological disease-modifying anti-rheumatic drug (bDMARD) which inhibits Interleukin 6 (IL-6) pathway through blockade of its receptor. At present, there is a lack of evidence to recommend the treatment of one bDMARD over another.(1) Seeking for genetic biomarkers to predict response to treatment could be key towards a personalized treatment strategy in rheumatology.(2)Objectives:We aimed to evaluate whether functional single nucleotide polymorphisms (SNPs) in the IL6R gene could predict response and/or toxicity to TZC in Caucasian patients diagnosed with RA.Methods:Retrospective analytical preliminar study of a cohort of 31 patients diagnosed with RA (ACR/EULAR 2010 criteria) who received treatment with TCZ within the last 10 years. Epidemiological, clinical and laboratory data were collected. DNA was extracted from EDTA blood samples. Three SNPs in the IL-6 receptor gene (rs12083537, rs2228145, rs4329505) were genotyped by real-time PCR with TaqMan probes. The associations between polymorphisms and clinicopathological features were evaluated using parametric tests. Efficacy was assessed as the difference of DAS-28 CRP at 6 months. The toxicities recorded were hepatotoxicity, infections, hypersensibility, gastrointestinal, hematological and dyslipidemia.Results:The 31 DNA samples from patients included were mainly female (83.9%) and had a mean age at diagnosis of 46.8 years. The mean duration of treatment was 51.3 months and, previously to initiate TCZ, they received a mean of 2,6 csDMARD and 1,7 bDMARD.The more frequent adverse effects were hypertransaminasemia (22.6%) and neutropenia (32.3%). Most relevant epidemiologic and clinical data is shown in Table 1.Table 1.Clinical characteristics. RA=Rheumatoid Arthritis. CCP= anti-Cyclic Citrullinated Peptides. RF=Rheumatoid factor. csDMARDs= conventional synthetic Disease-modifying antirheumatic drug. bDMARD= biological Disease-modifying antirheumatic drug. BMI=Body Mass Index. Sc=subcutaneous. Ev=endovenous. DAS28= Disease Activity Score in 28 jointsSex (n=31), n (% women/men) 26/5 (83,9%/16,1%)Age at diagnosis (n=31), years +- SD 46,8+- 12,8Erosive RA (n=31), n(%) 14 (45,2%)Anti-CCP positive (n=31), n(%)UI+- SD 23 (74,2%)259,7 +- 137,3RF positive (n=31), n (%)UI+-SD 21 (67,7%)189,4+- 114Previous csDMARD (n=31), n°+-SD2,6 +-1,3Previous bDMARD (n=31), n°+- SD1,7 +- 1,4BMI (n=29), mean +- SD29,3+- 5,1Duration of treatment (n=31), months +-SD51,3 +- 36,3-Active treatment (n=12)-80,9+- 18,3-Finished treatment (n=19)-32,6+- 32,2Route of administration (n=31), n (%) sc/ev 11/20 (35,5/64,5)Basal DAS28 (n=30), mean+- SD5,3 +- 1,1DAS28 reduction at 6 months (n=28), mean+-SD2,9 +-1,1The univariate analyses showed that the rs2228145 variant was statistically associated with differences in DAS28 reduction at 6 months (p=0.042). Regarding efficacy, we also found a trend with the SNP rs4329505 (p=0.173), which could achieve statistical significance with the projected inclusion of more patients. No associations were found regarding adverse effects.Conclusion:The rs2228145 polymorphisms in the IL6R gene may be considered as a pharmacogenetic biomarker of TCZ response in RA patients. More studies are required in order to investigate the clinical use of pharmacogenetic biomarkers in rheumatic diseases.References:[1]Smolen, Josef S., Robert B., et al. 2020. “EULAR Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-Modifying Antirheumatic Drugs: 2019 Update.” Annals of the Rheumatic Diseases 79 (6): 685–99.[2]Tarnowski, Maciej, Agnieszka Paradowska-Gorycka, et al. 2016. “The Effect of Gene Polymorphisms on Patient Responses to Rheumatoid Arthritis Therapy.” Expert Opinion on Drug Metabolism & Toxicology 12 (1): 41–55.Disclosure of Interests:None declared

Background:Gout is the most common inflammatory arthritis in adults. It is caused by the chronic deposition of monosodium urate crystals in joints. Hypertension, diabetes mellitus, chronic kidney disease (CKD) and cardiovascular disease are highly prevalent in gout patients.Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids or colchicine are the first line therapeutic agents for flares. These drugs can be contraindicated in a large group of gout patients. Off label prescription of IL-1 receptor blockage with anakinra can be an alternative for this complex patients.Objectives:The main objective of this study is to perform a scoping review about patient characteristics, comorbidity, effectivity and safety profile of patients with gout treated with anakinra.Methods:A total of 1119 citations were screened. The reviewers performed a two-stage screening by title/abstract and full-text screening. Thirty six articles that finally met selection criteria, were included for data extraction and synthesis. Treatment duration of ≥12 weeks was considered chronic.Results:Four hundred forty three patients were included in the study. 20 patients (4,5%) received chronic treatment and 423 (95,5%) flare treatment. Outcomes from 496 flares were finally analyzed.The mean age of the patients was 63.6 years and 84% were men. The clinical presentation was polyarticular in 47.9% and tophaceous gout in 66.5%. Some of these patients presented atypical forms of the disease such as spinal gout, autoinflammatory syndromes or sternoclavicular joint arthritis.Most of the patients presented comorbidities, the most prevalent being arterial hypertension in 127 (70.5%) and chronic kidney disease (≥ 3 stage) in 220 (51.8%). History of transplant in 37 (14.6%) with stem cell, kidney, heart, and liver transplant. More than half of patients had more than one associated comorbidity. Demographic and clinical characteristics of gouty arthritis patients are presented in Table 1. Flare was present in admitted patients in 260 (57.5%). Anakinra was administered in 52 patients with an active infection.Different treatment regimens were described. Daily administration was used in 98% of the patients. 92.8% of the flares were treated seven days or less, being the three days regimen the most prevalent. In the chronic group the longest treatment reported was 5 years.Efficacy of treatment with anakinra was evidenced, in flare 426 patients (93%) and chronic 19 patients (91%). Overall, anakinra was well tolerated. In the case of flares, thirty-three (7.9%) adverse effects related to anakinra administration were registered: seven (1.6%) site injection reactions, five (1.1%) reversible hematological alterations and five acute infections (H1N1, herpes zoster, severe cold, pulmonary abscess and nosocomial pyelonephritis). In chronic treated patients, adverse infectious events were more prevalent, seven (32%) infections (Staphylococcus aureus tophus (2), Staphylococcus aureus lung abscess, erysipela of the leg, Streptococcus B urinary tract infection, Staphylococcus aureus knee arthritis and tuberculous cervical lymphadenitis).Conclusion:Anakinra has been shown to be effective and safe in treatment for flares in gout complex or resistant patients. It has been shown in multiples scenarios like active infections, dialysis, transplants, chronic kidney disease, tophi and polyarticular disease refractory to standard treatment. It has also shown its effectiveness as chronic treatment, but there are more concerns about its safety. These findings need to be confirmed with controlled clinical trials for anakinra inclusion in treatment recommendations in special situations of flares in complex or resistant gout patients.Disclosure of Interests:None declared.

Background:Cryoglobulinemia (CG) is a rare phenomenon, which is defined as the persistent presence in serum of abnormal immunoglobulins (Igs) that precipitate in vitro at less than 37°C and dissolve when the temperature rises again. Is related to hematological disorders, infections and autoimmunes diseases.Objectives:To describe the differential clinical features, serological and demographics in a cohort of patients diagnosed with CG.Methods:We describe a retrospective cohort of 252 cryoglobulin (Cg) positive samples, obtained from a database from the immunology laboratory of a tertiary hospital (November 2018-November 2019). We obtained 182 patients with CG, classified according to their etiology into 4 groups: 1)Rheumatic diseases (RD) that includes rheumatoid arthritis, Systemic lupus erythematosus, Sjögren´s syndrome and Systemic scleroderma, 2)Hepatotropic viruses (HV) with patients diagnosed with Hepatitis C virus, B virus and both, 3)Hematological diseases (HD) and 4)Essential cryoglobulinemia (CGE). Demographic variables, clinical and serological data were collected. A comparative analysis was performed with the Mann-Whitney U test and the multivariate Kruskal-Wallis test, nonparametric variables were compared using a Wilcoxon test. Ten patients, with more than one disease from 4 groups, were excluded from the study.Results:Out of 182 reviewed patients, 172 were included in the study. Mean age at diagnosis was 59.7(±14.0). Demographic, clinical and laboratory characteristics are described in table 1. Mixed CG was the predominant subtype, in 116 (67.4%) patients. The most prevalent CG-associated diseases were HV infection with 91(53%) patients. CGE mostly presented with cutaneous manifestations (p=0.0001), particularly purpura. In RD group the presence of Raynaud and non-erosive arthritis (p=0.0001) was relevant. Laboratory findings showed that CG titration varies according to the etiology, being HD the one with the highest values with 292.2 (±546.2). There is significant difference in terms of the average of rheumatoid factor (RF) being higher in the group by CGE. On other hand, the group HV presented more consumption of complement, and showed the lowest average p=0.0001, without more severe clinical manifestations.RD (n=47)HV (n=91)HD (n=17)CGE (n=17)Gender,n(%) F42 (89.4)57 (62.6)7 (41.2)11 (64.7)Age at dg, years, (± SD)60.6 (±14)59.6 (±13.1)61.1(±16.6)56.3(±20.8)p=0.8CLINICAL CHARACTERISTICSSkin n (%)18 (38.3)10 (11.0)2 (11.8)9 (52.9)pRaynaud n (%)14 (29.8)1 (5.9)3 (17.6)pPurpura n (%)6 (12.8)9 (9.9)2 (11.8)6 (35.3)p=0.04Acrocyanosis n (%)6 (12.8)1 (5.9)p=0.0033Ulcers n (%)3 (6.4)2 (2.2) -2 (11.8)p=0.19Peripheric Neuro n (%)10 (21.3)9 (9.9)1 (5.9)4 (23.5)p=0.13N-E arthritis n (%)22 (46.8)8 (8.8)1 (5.9)4 (23.5)pGMN n (%)5 (10.6)3 (3.3)1 (5.9)3 (17.6)p=0.11LABORATORYCg (mg/dL) x (± SD)26.7 (±63.2)65.8 (±256.5)292.4 (±546.2)47.59 (±79.1)pIsotype IgG, n (%)G+M 26 (55.3)G+M 72 (79.1)M 8 (47.1)G+M 12 (70.6)β2M (≥1.8 mg/L), n (%)7/40 (17.5%)1/5 (20.0%)3/12 (25.0%)-p= 0.44RCP (mg/L) p 5010.3 (±26.2)3.9 (±3.0)13.4 (±18.3)8.5 (±12.0)p= 0.47ESR (mm/h) p5040.0 (±28.5)20.3 (±20.2)35.4 (±35.1)24.5 (±25.0)p= 0.0003RF + (>20UI/mL), n (%)19/46 (41.3)44/86 (51.2)5/11 (45.5)7/17 (41.2)p= 0.09p5090.6 (±175.9)161.0 (±219.5)94.8 (±135.6)284.5 (±619.3)pC3 ()20 (42.6)47 (51.6)3 (17.6)3 (17.6)p= 0.13x (± SD)90.1 (±28.6)68.5 (±10.8)99.1 (±29.0)114.8 (±12.7)pC4 ()17 (36.2)36 (39.6) -3 (17.6)p= 0.02x (± SD)15.6 (±9.0)7.6 (±3.5)20.4 (±7.4)21.1 (±9.5)pConclusion:In our cohort, not all patients with CG presented clinical manifestations being those associated with CGE and RD those with the highest skin and joint expression. The most prevalent association of CG continues to be the HV and we confirmed the characteristic decrease in C3 and C4 complement levels, together with the positivity for RF.Disclosure of Interests:None declared

Background:Patients with autoimmune inflammatory rheumatic diseases (AIIRD) have a higher burden of infectious diseases compared to the general population. This could be explained by the disturbances in their immune system response, comorbidities and immunosuppressive treatment.Vaccination is the most effective measure to prevent infections.Objectives:To describe a cohort of patients with AIIRD referred to the infectious disease´s unit according to the vaccination protocol.Methods:Restrospective and descriptive study of a cohort of 286 patients with AIIRD who were evaluated in the rheumatology service of a tertiary hospital in Barcelona and referred to the infectious disease´s unit according to the vaccination protocol among 1 year,between January 1rst December 31st, 2019. The vaccination protocol included serologies of human immunodeficiency virus,hepatitis A,B and C, varicella zoster,tuberculosis,measles,mumps and rubella virus.The recommended vaccines were H.influenzae b,S.pneumonia,influenza,hepatitis A and B(immunity absence),meningococcus c,tetanus – diphtheria (low antigenic load),poliomyelitis and human papillomavirus (not vaccinated).The patients included were diagnosed with a rheumatologic condition under immunosuppressive therapy. Demographic variables,diagnosis,treatment,vaccines administered,infections and adverse effects were collected.Results:Of 286 patients reviewed the mean age was 61, 4 (±14.4) years. The characteristics of the cohort are shown in Table 1. Most of the patients used csDMARDs 149 (52.1%), 77(26.9%) patients used combined treatment. Measles and rubella are part of the triple virus vaccines included in the systematic Spanish vaccination schedule, in our cohort 20 (7%) patients had negative serologies for measles and 26 (9%) for rubella. 57 (20%) patients had latent TB with positive Quantiferon.Forty-one (14.3%) were vaccinated before receiving immunosuppressive treatment. The less administered vaccine was influenza with 44.9% (vaccination rate in Spain in healthy population, in 2019-2020 was 51.2%).No serious adverse effects were reported in relation to the vaccination. The infectious complications during the follow-up period were bronchopneumonia in a patient with RA treated with certolizumab (1), herpes zoster infection in RA on adalimumab(1), recurrent otitis in RA on adalimumab(1), mycobacterium avium infection in RA on etanercept(1), TB reactivation in RA with GCs and csDMARDs(1) and Papilloma virus infection in SpA on ustekinumab (1).Table 1.CHARACTERISTICS OF COHORT OF PATIENTSSex n % (women/men)193/93 (67,5/32,5)Age, years ± DE61.4 ± 14.4Diagnoses AIIRD, n (%)Rheumatoid arthritis n (%)164 (57.3)Systemic lupus erythematosus n (%)6 (2.1)Sjögren´s syndrome n (%)9 (3.1)Systemic sclerosis n (%)1 (0.35)Inflammatory myopathie n (%)5 (1.7)Vasculitis n (%)36 (12.6)Polymyalgia rheumatica n (%)4 (1.4)Spondyloarthropathy n (%)46 (16.1)Others n (%)15 (5.2)Treatment AIIRDGCs n (%)116 (40.7)csDMARDs n (%)149 (52.1)bDMARDs n (%)80 (27.8)tsDMARDs n (%)7 (2.4)Others1 n (%)12 (4.2)GCs + csDMARDs n (%)59 (21)GCs + bDMARDs n (%)14 (4.9)GCs + csDMARDs + bDMARDs n (%)4 (1.4)VaccinesPCV 13 n (%)283 (99)PPSV23 n (%)265 (93)HiB n (%)265 (93)NM n (%)247 (86.7)Influenza n (%)128 (44.9)HBV n (%)121 (42.3)Vaccination before IS n (%)41 (14.3)Vaccination with IS n (%)244 (85.3)Other: Behcet,Adult Stills,Relapsing polychondritis,IGg4 related disease,SarcoidosisOthers1: Mycophenolic acid,cyclosporine and tacrolimusConclusion:In our cohort, the vaccination protocol proved to be a good tool to improve the vaccination rate of rheumatological patients, despite this, the vaccination of Hepatitis B and specially of influenza, continues to have a lower prevalence to general population.The vaccines were effective since none of the preventable infections occurred during follow up, despite the use of an immunosuppressant. Vaccination showed a good safety profile, without reported serious adverse effects or worsening of the underlying disease.Disclosure of Interests:None declared

Background:Gout is the most prevalent inflammatory arthritis. Gout is chronic inflammatory deposition disease related to an increase of cardiovascular (CV) events and mortality. Subclinical chronic inflammation has been demonstrated in this patients but not its relation with the monosodium urate (MSU) crystal deposit size and the number of CV risk factors.Objectives:To study the subclinical inflammation in intercritical gout patients and its possible relation to the estimated size of the crystal deposition and the number of CV risk factors.Methods:To analyze subclinical inflammation we performed a secretome analysis and a cytokine and adiponektine plasma levels quantification (IL-1β, IL-18, IL-6, sIL-6R, TNFα, CXCL-5, RANTES, leptin, resistin and adiponectin) in a cohort of gout patients. As nowadays it is not feasible to determinate the whole body deposit of MSU crystals we created three different MSU crystal deposit size patient groups using an indirect clinical and analytical classification to estimate it. Then we compared cytokine levels between healthy donors and gout patients. We also compared cytokine levels between the different crystal size deposition groups and studied its association to the number of CV risk factors.Results:Ninety consecutive patients attending a Crystal Arthritis Unit were studied. Mean age was 68.27 (28-101) years. 81.1% were male. Clinical gout evolution was of 10.1±9.8 years. 77.5% were on urate lowering treatment. 24% had tophaceous gout. Mean uric acid was 6.3±2.1 mg/dl with 47.1% of them being on target. Hypertension was present in 68.9%, diabetes mellitus in 18.9%, dislipemia in 48.9%, BMI>30 in 32.9%, abdominal obesity in 50% and 16.1% suffered from ischemic heart disease. From the 102 molecules studied in the secretome analysis in 56 there was at least a 20% difference between donors group and any of the deposition groups. In 74% of them gout patients secreted lower levels. IL-18, sIL-6R, RANTES, leptin and adiponectin were higher in patients than in healthy donors. IL-18, sIL6-R, RANTES and CXCL5 levels were associated to the size of the crystal deposits. IL-18, sIL-6R, RANTES and leptin were higher in gout groups with CV risk factors. IL-18, sIL6-R, RANTES and leptin were higher in gout patients with no risk factors when compared to healthy donors with no risk factors. We found no differences when comparing urate lowering treated and non-treated patients.Conclusion:Our results demonstrate that some proinflammatory cytokines and metabolic proteins are raised in intercritical gout patients. Some of them are different from the flare/inflammasome expected ones. In some cytokines this elevation is related to the size of the monosodium urate crystal deposit and/or to the number of cardiovascular risk factors. This cytokine changes could help to explain the increase of the cardiovascular events in gout patients.Disclosure of Interests:Cesar Diaz-Torne Grant/research support from: Received a grant from Grünenthal, Maria Angels Ortiz: None declared, Sicylle Jeria Navarro: None declared, Andrea Garcia-Gullien: None declared, Lluis Sainz: None declared, Hector Corominas: None declared, Silvia Vidal: None declared

Background:Currently, there are no biomarkers to predict respiratory worsening in patients with Coronavirus infectious disease, 2019 (COVID- 19) pneumonia.Objectives:We aimed to determine the prognostic value of Krebs von de Lungen-6 circulating serum levels (sKL-6) predicting COVID- 19 evolving trends.Methods:We prospectively analyzed the clinical and laboratory characteristics of 375 COVID- 19 patients with mild lung disease on admission. sKL-6 was obtained in all patients at baseline and compared among patients with respiratory worsening.Results:45.1% of patients developed respiratory worsening during hospitalization. Baseline sKL-6 levels were higher in patients who had respiratory worsening (median [IQR] 303 [209-449] vs. 285.5 [15.8-5724], P=0.068). The best sKL-6 cut-off point was 408 U/mL (area under the curve 0.55; 33% sensitivity, 79% specificity). Independent predictors of respiratory worsening were sKL-6 serum levels, age >51 years, time hospitalized, and dyspnea on admission. Patients with baseline sKL-6 ≥ 408 U/mL had a 39% higher risk of developing respiratory aggravation seven days after admission. In patients with serial determinations, sKL-6 was also higher in those who subsequently worsened (median [IQR] 330 [219-460] vs 290.5 [193-396]; pConclusion:sKL-6 has a low sensibility to predict respiratory worsening in patients with mild COVID-19 pneumonia. Baseline sKL-6 ≥ 408 U/mL is associated to a higher risk of respiratory worsening. sKL-6 levels are not useful as a screening tool to stratify patients on admission but further research is needed to investigate if serial determinations of sKL-6 may be of prognostic use.References:[1]Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62. 5.[2]Tian W, Jiang W, Yao J, Nicholson CJ, Li RH, Sigurslid HH, et al. Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis. J Med Virol. 2020.[3]Wang D, Li R, Wang J, Jiang Q, Gao C, Yang J, et al. Correlation analysis between disease severity and clinical and biochemical characteristics of 143 cases of COVID-19 in Wuhan, China: a descriptive study. BMC Infect Dis. 2020;20(1):519.Disclosure of Interests:None declared.

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease with variable clinical features and a complex physiopathology. In 2019, EULAR and ACR have jointly developed new classification criteria with both high sensitivity and specificity. These criteria have the particularity of including the presence of ANA as an obligatory entry criterion and the existence of clinical and immunological domains with weighted scores.Objectives:To evaluate the performance and characteristics of the ACR/EULAR 2019, SLICC 2012 and ACR 1997 classification criteria in a cohort of SLE patients with longstanding disease.Methods:Descriptive observational study that enrolled a cohort of SLE patients with longstanding disease followed in a tertiary level hospital. Demographic and clinical data were gathered along with the fulfillment of classification criteria. The sensitivity of each classification criteria and the statistically significant associations between criteria fulfillment and clinical and immunological data were calculated. Statistical analyses were performed using the Chi2, T-student and ANOVA tests. Statistical significance was assumed in p values Results:A total of 79 patients (88.6% women) with a mean age of 51.8±14 years, disease duration of 15.2±11.5 years and SLEDAI of 2.65±2.1 were included. The sensitivity of the different classification criteria was 51.9% for ACR 1997, 87.3% for SLICC 2012 and 86.1% for ACR/EULAR 2019 (Table 1).Table 1.Sensitivity and average scores.ACR/EULAR 2019SLICC 2012ACR 1997Sensitivity (%)86.187.351.9Average score of patients classified as SLE(±SD)18.6±5.85.3±1.45±0.9Average score of patients NOT classified as SLE(±SD)6.1±2.52.8±0.42.8±0.851.9% of patients met all three classification criteria, 29.1% met SLICC 2012 and ACR/EULAR 2019, 5% only met SLICC 2012 and 3.7% exclusively met ACR/EULAR 2019. 11.4% of patients did not meet any classification criteria and were characterized by having a low SLEDAI (0.6±0.9) and fulfilling only skin domains (alopecia or oral ulcers), antiphospholipid antibodies or hypocomplementemia.Statistically significant associations were found between meeting ACR/EULAR 2019 classification criteria and the presence of low C3 and C4 (pIn the SLICC 2012 evaluation, significant associations were found between meeting these criteria and the presence of arthritis (pFullfilment of ACR 1997 was associated to the presence of malar rash (pThe Kappa concordance coefficient among classification criteria is detailed in Table 2.Table 2.Kappa concordance coefficient.ACR/EULAR 2019 - SLICC 2012ACR/EULAR 2019 - ACR 1997SLICC 2012 - ACR 1997Kappa concordance coefficient0.610.270.30Conclusion:The ACR/EULAR 2019 classification criteria maintain a high sensitivity similar to the SLICC 2012 in SLE patients with longstanding disease, both of which are much higher than ACR 1997. Patients with serological, articular or renal involvement are more likely to meet SLICC 2012 or ACR/EULAR 2019 criteria. It is noteworthy the relevance of dermatological manifestations in ACR1997 classification criteria against the increased weight that a better understanding of SLE physiopathology has provided to analytic and immunological criteria in the subsequent classification criteria.Disclosure of Interests:David Lobo Prat: None declared, Berta Magallares: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, HyeSang Park: None declared, Patricia Moya: None declared, Ignasi Gich: None declared, Ana Laiz: None declared, Cesar Díaz-Torné: None declared, Ana Milena Millán Arciniegas: None declared, Susana P. Fernandez-Sanchez: None declared, Hector Corominas: None declared

With the aim to develop and validate a clinical + ultrasound (US) inflammation score in rheumatoid arthritis (RA) for use in clinical practice, a mixed-method study was conducted. The theoretical development of the index was achieved with qualitative methodology (discussion group and Delphi survey). Subsequently, a cross-sectional study was carried out to analyse issues related to scoring and validation of the new index. RA patients underwent clinical [28 swollen and tender joints count, patient and physician global assessment (PhGA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)], and US assessments [synovitis or tenosynovitis by grey-scale (GS) and power Doppler (PD) of 42 structures]. An index was created based on statistical models and expert interaction. Construct validity was tested by correlation with DAS28, SDAI, CDAI, and PhGA. Reliability was evaluated in a subgroup of patients with the intraclass correlation coefficient (ICC). US assessment, CRP, and swollen joints were the items that passed the prioritization phase (Delphi study). For the cross-sectional study, 281 patients were randomly divided into design (n = 141) and validation samples (n = 140). The combination of US sites chosen (7 bilaterally) detected the maximum proportion of synovitis and PD present. Three scoring methods were tested: semiquantitative (0-3 GS + 0-3 PD), dichotomous (0/1 GS + 0/1 PD), and qualitative (0/1 based on algorithm). All showed strong correlation with activity measures (? = 0.60), and reliability (ICC 0.89-0.93). The index with best parameters of validity, feasibility, and reliability was the qualitative. The final index chosen was the sum of swollen joint count, US qualitative score, and CRP. The UltraSound Activity score is a valid and reliable measure of inflammation in RA equal to the sum of 28 SJC, a simplified (0/1) US assessment of 11 structures and CRP. It is necessary further investigation to demonstrate additional value over existing indices.

ObjectivePsoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA.MethodsWe performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case–control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA.ResultsWe identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDRConclusionThese findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

Background:Obesity is a predictor for the development of psoriatic arthritis (PsA) with a negative prognostic impact.Objectives:We aimed to describe and characterize patients with PsA according to the Body Mass Index (BMI) in a joint Rheumatology-Dermatology unit (PAIDER).Methods:We retrospectively reviewed patients diagnosed with PsA according to CASPAR criteria visited between May 2012 and May 2019 at the PAIDER clinic of our center. Data on demographic and anthropometric features, serologic findings, source of referral, cardiovascular risk factors and biological treatment were collected from clinical records. Patients were classified according to the WHO International Classification of nutritional status in normal weight (BMI 18.5-24.9 Kg/m2), overweight (BMI 25-29.9 Kg/m2) and obesity (BMI≥30 Kg/m2). A descriptive analysis was performed, and the differences between groups were evaluated using Chi2, T-Student and ANOVA tests. P-values Results:During the study period 393 patients (50.6% women) with a mean age of 52.47 ± 13.21 years were evaluated. Baseline characteristics are shown in table 1.Table 1.Baseline characteristicsTotaln=393Female, n (%)199 (50,6)Age, yrs, mean ±SD52,47 (13,21)Source of referral, n (%) Dermatology117 (29,8) Rheumatology219 (55,7) Primary Care and Others22 (5,6)Smoker, n (%)97 (25,8)High Blood Pressure (HBP), n (%)106 (27,7)Diabetes, n (%)48 (12,5)Hypercholesterolemia, n (%)98 (25,8)Hyperuricemia, n (%)32 (8,6)HLA-B27 positive, n (%)68 (21,6)BMI, Kg/m2, mean ±SD28,15 (5,87)Biological treatment, n (%)166 (43,2)The mean BMI was 28.15 ± 5.87 kg/m2. 112 patients (32%) were overweight with a mean BMI of 27.46 ± 1.55 kg/m2and 118 patients (34%) were obese with a mean BMI of 34.42 ± 5.08 kg/m2. Of the obese patients, 80 (67.8%) had obesity grade 1, 28 (23.7%) grade 2 and 10 (8.5%) grade 3.Characteristics of the patients according to BMI categories are shown in Table 2.Table 2.Characteristics according to BMINormal weightn= 118Overweightn= 112Obesityn=118P valueFemale, n (%)66 (55,9)52 (46,4)62 (52,5)nsAge, yrs, mean ±SD47,92 (14,08)54,71 (11,75)54,48 (11,54)Source of referral, n (%)Ns Dermatology35 (33,7)37 (35,2)34 (30,9) Rheumatology63 (60,6)61 (58,1)70 (63,6) Primary Care and Others6 (5,8)7 (6,7)6 (5,5)Smoker, n (%)37 (33)23 (21,1)31 (26,7)nsHigh Blood Pressure (HBP), n (%)12 (10,5)37 (34,3)41 (35)Diabetes, n (%)7 (6)9 (8,3)30 (25,6)Hypercholesterolemia, n (%)19 (17)24 (22,2)45 (38,5)0,001Hyperuricemia, n (%)5 (4,4)7 (6,8)19 (16,7)0,004HLA-B27, n (%)27 (28,7)17 (17,9)13 (12,6)0,016BMI, Kg/m2, media ±DE22,58 (1,78)27,46 (1,55)34,42 (5,08)-Biological treatment, n (%)47 (41,2)45 (40,9)66 (55,9)0,032We observed that mean age was significantly higher in obese patients (p Conclusion:- Almost 70% of patients with PsA visited in the PAIDER clinic of our center have a BMI above normal and more than a third of them are obese, mostly grade 1.- In our joint clinic there are no differences in BMI regarding the source of referral of the patients.- Patients with obesity are older, have more cardiovascular comorbidities and receive more biological treatment significantly, which increases the complexity of their management and worsens the prognosis.Disclosure of Interests:Andrea García-Guillén: None declared, Ana Laiz: None declared, Anna Lopez-Ferrer: None declared, HyeSang Park: None declared, Patricia Moya: None declared, Berta Magallares: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, Ana Milena Millán Arciniegas: None declared, Cesar Díaz-Torné: None declared, Sicylle Jeria: None declared, Hector Corominas: None declared

Background:Lyme disease (LD) is a multisystemic animal-borne disease caused by spirochetes of theBorrelia burgdorferi s.lcomplex and transmitted by ticks of the speciesIxodes ricinus. In Spain, most cases occur in rural areas of the north-east region with a peak of maximum incidence between spring and early autumn. The diagnosis is based on a history of potential exposure to ticks, the recognition of characteristic clinical manifestations and serological testing.Objectives:To assess the suitability of serological study for the diagnosis of LD in an urban area.Methods:Retrospective observational study that included all LD serology tests made between April 2017 and September 2019 at a tertiary hospital in Barcelona covering a population of 450,000 people. Demographic data and the medical department that requested the serology test were collected along with serology test results. The medical records of patients with positive serology were consulted to identify which patients were finally diagnosed with LD along with their clinical manifestations, treatment and outcome.Results:A total of 574 serological tests were included and 78 (13.59%) of them were positive. Only 1.04% (6) of all serological tests belonged to patients finally diagnosed with LD. The department that made most requests was Neurology (37.3%) followed by Infectious Diseases (21%), Internal Medicine (14.5%), Emergency Medicine (4.7%), Dermatology (4.5%), Critical Care Medicine (2.3%) and Rheumatology (2.1%). 50% of the diagnosed patients were women with a mean age of 57.7±7.7DE years. In 50% of diagnosed cases, patients remembered a tick bite during activities in the mountain or rural areas. The most common clinical manifestations were erythema migrans (67%), non-inflammatory arthralgias (50%), fatigue and malaise (67%), together with one case of meningoencephalitis and one of knee monoarthritis. All diagnosed patients received antibiotic treatment with ceftriaxone (33%) or doxycycline (66%). Only one patient presented post-Lyme syndrome.The serological test for LD in our center had a total individual cost of 15.75 eur, so the cost of the 574 requests was 9,040.5 eur. 7,812 eur corresponded to negative results and 1,134 eur to false positive results.Conclusion:Our study indicates the overuse of diagnostic testing for LD with implications for patient care and cost-effective health management. In the absence of a history of potential exposure to infected vector ticks or characteristic clinical manifestations, unnecessary microbiological tests should not be performed.Disclosure of Interests:David Lobo Prat: None declared, Luís Sainz Comas: None declared, Virginia Pomar: None declared, Ana Milena Millán Arciniegas: None declared, HyeSang Park: None declared, Andrea García-Guillén: None declared, Sicylle Jeria: None declared, Ana Laiz: None declared, Berta Magallares: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, Patricia Moya: None declared, Cesar Díaz-Torné: None declared, Susana P. Fernandez-Sanchez: None declared, Hector Corominas: None declared

Aim: Variation at PDE3A-SLCO1C1 locus has been recently associated with the response to anti-TNF therapy in rheumatoid arthritis. We undertook the present study to determine whether PDE3A-SLCO1C1 is also associated with the response to anti-TNF therapy in psoriatic arthritis. Patients & methods: Genomic DNA was obtained from 81 psoriatic arthritis patients that had been treated with anti-TNF therapy. PDE3A-SLCO1C1 SNP rs3794271 was genotyped using Taqman realt-time PCR. The clinical response to anti-TNF therapy was measured as the change from baseline in the level of disease activity according to the DAS28 score. Results: A significant association between rs3794271 and anti-TNF response in psoriatic arthritis was found (beta = -0.71; p = 0.0036). Conclusion: PDE3A-SLCO1C1 locus is also associated with response to anti-TNF therapy in psoriatic arthritis. Original submitted 12 May 2014; Revision submitted 18 August 2014

Ultrasonography (US) has shown to be more sensitive than physical examination for diagnosis and assessment of rheumatoid arthritis (RA). It is also a useful approach for accurate monitoring and intensive treatment adjustment. However, there is limited information concerning the impact of US on therapeutic decision-making in routine daily practice. A single-center cross-sectional study in routine daily practice was conducted to determine the percentage of patients with rheumatoid arthritis (RA) in which treatment decision was modified on the basis of results of musculoskeletal ultrasonography. All consecutive patients with RA visited for the control of their disease between September and November 2014 were included. Patients were visited by their attending rheumatologist, who made a therapeutic decision according to the results of physical examination and laboratory tests. Thereafter, a musculoskeletal ultrasound (US) was performed by an independent expert sonographer. According to US findings, a change in therapeutic decision was considered, and categorized as 'negative' (maintenance of the therapeutic attitude) or 'positive' (intensification or reduction of treatment). A total of 78 patients (83% women, mean age 63.3 years) were included. In 29 patients [32%, 95% confidence interval (CI) 26.5-48.9], a change in the therapeutic decision was made, which included intensification of treatment in 18 (62.1%) and reduction of treatment in 11 (37.9%). Change of treatment was more frequent in patients with intermediate disease activity (low and moderate) than in those in clinical remission or with high activity (41.4 vs. 25%), in men than in women (53.8 vs. 33.8%), and in the presence than in the absence of bone erosions (43.6 vs. 21.7%), although differences were not statistically significant. We conclude that in patients with RA, joint US is a relevant complementary tool for treatment decisions in daily practice, particularly in patients with intermediate disease activity.

Soluble factors released from platelets can modulate the immune response of leukocytes. We and others have recently found that T lymphocytes with bound platelets have reduced proliferation and IFN-γ and IL-17 production. Thus, we speculate that if we induce the binding of platelets to lymphocytes, we will be able to regulate the inflammatory response. When we cocultured platelets with lymphocytes at different ratios, we were able to increase the percentage of lymphocytes with bound platelets. The coculture of platelets with lymphocytes in the presence of stimulation decreased the production of IFN-γ and TNF-α, T cell proliferation, and the expression of CD25, PD-L1, and SLAM. However, this coculture increased CD39 expression. All of these effects were dependent on the dose of platelets and operated indistinctly with platelets from different healthy donors. When platelets were cocultured in the same compartment with lymphocytes, we observed less IFN-γ and TNF-α production and T lymphocyte proliferation than in cultures with platelets separated from lymphocytes by a 0.4-μm pore size filter. The binding of platelets to lymphocytes was blocked with anti–P-selectin Abs, and when this occurred we observed higher IFN-γ and TNF-α production than in nonblocked conditions. The cocultures of platelets with synovial fluid cells from rheumatoid arthritis patients reduced inflammatory cytokine production and increased IL-10 production. These results suggest that platelet binding to lymphocytes effectively regulates T lymphocyte function. This mechanism could be easily applied to reduce inflammatory responses.

Objectives The LILRB1 gene has recently been associated with rheumatoid arthritis (RA) susceptibility in HLA-DRB1-shared epitope (SE) negative Japanese individuals. Since the contribution of the LILRB1 polymorphism to RA susceptibility may vary among ethnic populations, we examined this association in a group of Caucasian patients. The frequency of LILRB1 alleles was also determined in patients according to the presence of DRB1-SE. Methods Samples from 103 RA patients and 107 healthy controls were randomly collected. Polymorphism of the LILRB1 gene was analyzed by sequencing with primers that amplified intron 3 and exon 4. Results The frequencies of LILRB1 alleles in RA patients did not differ from those of controls. However, when patients and controls were grouped according to SE, the PE-01/01 genotype was less frequent in negative-SE patients than in controls. Whereas SE is associated with higher anti-CCP antibody levels, as expected, the production of anti-CCP antibodies was lower in negative-SE patients with PE-01/01 genotype. Moreover, radiographic damage in hand and feet of SE-negative PE-01/01 patients was less severe than in patients with other genotypes. Conclusions The participation of this LILRB1 polymorphism in the RA pathogenesis of this Caucasian cohort differed from that reported in a Japanese sample. Our findings suggest that the LILRB1-PE-01/01 genotype could exert a protective role in RA susceptibility and disease severity in the absence of SE.

Consensus exercises have identified and prioritized domains of measurement for studies in acute and chronic gout. In parallel, the technical properties of instruments for measurement in many of these domains have been assessed, with the main objective to consider the instruments in the context of the OMERACT filter of truth, discrimination, and feasibility. These data were presented and discussed at OMERACT 9 in the Gout workshop, in breakout groups, and at informal meetings of the gout group. In acute gout, instruments for domains of pain, joint swelling. joint tenderness, and patient and physician global assessment have been assessed. In chronic gout, some validation exercises have been performed in instruments for domains serum urate, tophus measurement, health-related quality of life (HRQOL). In voting at OMERACT 9, the Medical Outcomes Study Short-Form 36 was endorsed as a valid instrument for measurement of HRQOL. Methods of tophus measurement were considered to have met some criteria of the OMERACT filter, but these require further work, particularly regarding sensitivity to change over shorter time periods. Priorities for future research include measurement of joint inflammation in acute gout and disability in acute and chronic gout. (J Rheumatol 2009;36:2346-55; doi: 10.3899/jrheum.090371)

Objective: Much of what is known about the inflammatory response in the synovial membrane (SM) of patients with osteoarthritis (OA) comes from studies of synovial tissues from end-stage disease. In this study, we sought to better characterize the inflammatory infiltrate in symptomatic patients with early signs of knee CA, and to determine how inflammatory cell populations relate to the pattern of cytokine and degradative enzyme production. Methods: Study populations comprised patients with degenerative meniscal tears and early cartilage thinning undergoing arthroscopic procedures (early CA) and patients undergoing total knee replacement for end-stage OA. Quantitative real-time polymerase chain reaction (PCR) was used to measure expression of SM cytolkines and enzymes implicated in the pathogenesis of inflammatory arthritis and CA, as well as cell lineage-specific markers. We quantified synovial fluid (SF) cytokines and enzymes by enzyme-linked immunosorbent assay (ELISA) and SM cell populations by immunohistochemistry. Results: We found increased levels of SF interleukin-15 (IL-15) protein in the early knee OA patients when compared to end-stage OA. Both SF IL-15 protein and numbers of CD8 cells within SM correlated with matrix metalloproteinase-1 (MMP-1) and three levels. TNF-alpha, IL-6 and IL-21 were also detectable in the SF of the majority of patients, and IL-15 levels were associated with IL-6 levels. Conclusion: IL-15 is elevated in early knee CA, suggesting activation of an innate immune response in the SM. The association of IL-15 expression with CD8 transcripts and MMPs implicates this cytokine in OA pathogenesis and as a candidate therapeutic target. (C) 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Objective To characterize histologic alterations and inflammatory infiltrates in the synovium of patients with chronic septic arthritis (SeA). Methods Synovial membranes from patients with SeA (9 specimens; disease duration >4 weeks) were compared with specimens from patients with septic joint prosthesis loosening (septic total arthroplasty [SeTA]; 9 specimens), rheumatoid arthritis (RA; 25 specimens), osteoarthritis (25 specimens), and normal histology (10 specimens). Sections were stained with hematoxylin and eosin, tissue gram stain, and immunostains for von Willebrand factor (vWF; blood vessels), Ki-67 (dividing cells), CD15 (neutrophils), CD3 (T cells), CD20 (B cells), CD38 (plasma cells), and CD68 (macrophages). Results Gram stains were positive in all SeA and SeTA specimens. Mixed polymorphonuclear and mononuclear infiltrates predominated in SeA and SeTA. SeA could be differentiated from RA by higher densities of CD15+ cells (SeA:RA ratio 6.5:1; P < 0.001) or Ki-67+ cells (ratio 2.1:1; P = 0.012). The inflammatory infiltrate of SeTA was similar to SeA but contained fewer CD3+ cells (SeTA versus SeA 0.26:1; P = 0.009) and a tendency toward fewer CD20+ cells. Mean vascular density was strikingly increased in SeA (SeA:normal ratio 3.0:1; P < 0.001) and, to a lesser extent, in the vascularized areas of the SeTA specimens (SeTA:normal ratio 1.9:1). Ki-67/CD31 double immunostains demonstrated proliferating endothelial cells in small subintimal blood vessels, suggesting angiogenesis. Receiver operating characteristic curve analysis identified higher densities of CD15+ and Ki-67+ cells and vWF-positive vessels as histologic markers that differentiated SeA from RA. Conclusion This first analysis of the synovium in patients with chronic pyogenic arthritis identified dramatic neovascularization and cell proliferation, accompanied by persistent bacterial colonization and heterogeneous inflammatory infiltrates rich in CD15+ neutrophils, as histopathologic hallmarks.

To quantify inflammatory changes in synovial membranes from orthopaedic "non-inflammatory" arthropathies (Orth. A).Synovial membranes from patients with femur fracture, avascular necrosis of the femur, plica syndrome, and meniscus and/or ligament injury (n = 23); rheumatoid arthritis (n = 28); osteoarthritis (OA; n = 25); and from normal controls (n = 10) were assessed by light microscopy, a histological synovitis score, immunostaining for CD3, CD20, CD38, CD68, Ki-67 and von Willebrand factor, and with an immunohistochemical inflammation score.Orth. A histology varied between normal and markedly inflamed. Predominant abnormalities were mild lining hyperplasia, scattered inflammatory cells and small perivascular infiltrates. The synovitis score classified Orth. A as "mild synovitis". Inflammatory cells occurred frequently: CD68+ cells in 100% of Orth. A specimens; CD3+, 91%; CD38+, 70%; and CD20+, 39%. Orth. A had 36% greater lining thickness (p = 0.04), 40% higher vascular density (p = 0.009) and 51.3-fold higher CD38+ cell density (p = 0.02) than normal controls; and 60% fewer subintimal Ki-67+ cells (p = 0.003), 42% fewer CD68+ lining cells (p0.01) and 40% fewer subintimal CD68+ cells (p0.01) than OA. The immunohistochemical inflammation score was 2.2-fold higher in Orth. A than in controls (p = 0.048) and similar to OA, with three Orth. A specimens showing marked inflammation.Synovial membranes from "non-inflammatory" arthropathies featured neovascularisation and inflammation intermediate between normal and OA synovium. These results expand previous findings that mechanical joint injury may lead to a mild-to-moderate synovitis.

Objective.To determine whether there is an association between different capillaroscopic findings and pulmonary function tests in systemic sclerosis (SSc).Methods.We did a retrospective observational study in a cohort of patients with SSc and early SSc. Patients with at least 1 nailfold videocapillaroscopy (NVC) magnified 120× were included. Pathological findings were giant capillaries, angiogenesis, and density loss. Findings were compared with lung function values: percent expected value of forced vital capacity (FVC), DLCO, and FVC/DLCO ratio. Other variables collected were sex and SSc type, and the presence of digital ulcers (DU), interstitial lung disease (ILD), scleroderma renal crisis, and/or pulmonary hypertension (PH).Results.Of 136 patients with SSc, 85 had undergone an NVC. The frequency of ILD, DU, and PH was 24.1%, 28.7%, and 17.2%, respectively. Data analysis showed that patients with density loss had worse FVC% (86.91 ± 19.42 vs 101.13 ± 16.06, p < 0.01) and DLCO% (71.43 ± 21.19 vs 85.9 ± 19.81, p < 0.01) compared to those without.Conclusion.Patients with loss of density present worse FVC and DLCO values. Prospective studies are warranted to determine whether NVC is useful for studying pulmonary function in SSc.

Objective.The gout working group at the Outcome Measures in Rheumatology (OMERACT) 12 meeting in 2014 aimed to determine which imaging modalities show the most promise for use as measurement instruments for outcomes in studies of people with chronic gout and to identify the key foci for future research about the performance of these imaging techniques with respect to the OMERACT filter 2.0.Methods.During the gout session, a systematic literature review of the data addressing imaging modalities including plain radiography (XR), conventional computed tomography (CT), dual-energy computed tomography (DECT), magnetic resonance imaging (MRI), and ultrasound (US) and the fulfillment of the OMERACT filter 2.0 was presented.Results.The working group identified 3 relevant domains for imaging in gout studies: urate deposition (tophus burden), joint inflammation, and structural joint damage.Conclusion.The working group prioritized gaps in the data and identified a research agenda.

Considering the interplay of multiple STATs in response to cytokines, we investigated how IL-6 and its blocking affect STAT signaling in rheumatoid arthritis (RA). Leukocytes obtained from RA patients before and after tocilizumab treatment and healthy donors (HDs) were cytokine-stimulated and STAT phosphorylation was analyzed by cytometry. RA patients had significantly fewer pSTAT1+, pSTAT3+, and pSTAT6+ monocytes and pSTAT5+ lymphocytes than HDs. After 24 weeks of treatment, percentages of IFN gamma-induced pSTAT1+ and IL-10-induced pSTAT3+ monocytes in RA patients increased, reaching levels comparable to HDs. pSTAT1+ and pSTAT3+ cells correlated inversely with RA disease activity index and levels of pSTAT+ cells at baseline were higher in patients with good EULAR response to tocilizumab. IFN gamma-induced pSTAT1+ cells correlated inversely with memory T cells and anti-CCP levels. IL-10-induced pSTAT3+ cells correlated with Treg/Teff ratio. Our findings suggest that IL-6 blocking reduces the inflammatory mechanisms through the correction of STAT1 and STAT3 activation status. (C) 2015 Elsevier Inc. All rights reserved.

Objective To identify predictors of early response to tocilizumab (TCZ) in patients with active rheumatoid arthritis (RA) seen in daily routine clinical practice. Methods A multicenter ambispective observational study of 126 RA patients treated with TCZ as a first- or second-line biological therapy. The variables associated to achieve the therapeutic goal (remission defined as a DAS28-ESR Results TCZ was administered as the first biologic in 26% of patients. Overall, 34% of patients received TCZ as monotherapy. EULAR response and remission were obtained in 82% and 31% of patients at 3 months and in 86% and 40% at 6 months. In the multivariate analysis, the predictive factors increasing the likelihood of clinical remission at 3 months were baseline ESR > 30 mm/h (OR = 19.07, 95% CI: 2.720–133.716), baseline CRP > 10 mg/L (OR = 4.95; 95% CI: 1.464–13.826), and the presence of extra-articular manifestations of the disease (OR = 15.45, 95% CI: 2.334–102.319). The factors that decreased it were higher concentrations of hemoglobin (OR = 0.53, 95% CI: 0.319–0.910), higher baseline DAS28-ESR (OR = 0.30, 95% CI: 0.145–0.635) and the number of previous DMARDs (OR = 0.41, 95% CI: 0.221–0.779), and biological therapies used (OR = 0.33, 95% CI: 0.155–0.734). The only factor that remained statistically significant at 6 months was higher baseline DAS28-ESR (OR = 0.55, 95% CI: 0.347–0.877). No relationship was found with the neutrophil count or with the RF or ACPA positivity. Conclusion In routine clinical practice, strong acute phase response, the presence of extra-articular manifestations, and the number of previous DMARDs and biological therapies used may help to identify patients who will have a rapid response to TCZ. However, it is likely that no parameter will predict response if taken separately.

Rituximab therapy alters all aspects of B-cell participation in the disturbed immune response of rheumatoid arthritis patients. To determine the impact of B-cell depletion on other immune compartments, we analysed levels of soluble and surface interleukin-15 (IL-15) along with the frequency of IL-15-related subsets after rituximab treatment. We then studied the correlation of observed changes with clinical activity. Heparinized blood samples from 33 rheumatoid arthritis patients were collected on days 0, 30, 90 and 180 after each of three rituximab cycles. Serum cytokine levels were determined by ELISA. Interleukin-15 trans-presentation was analysed by cytometry. Flow cytometry with monoclonal antibodies was performed to analyse circulating cell subsets. Interleukin-15 was detected in the serum of 25 patients before initiating the treatment. Rituximab then progressively reduced serum IL-15 (138 +/- 21pg/ml at baseline, 48 +/- 18pg/ml after third cycle, P=0 center dot 03) along with IL-17 (1197 +/- 203pg/ml at baseline, 623 +/- 213pg/ml after third cycle, P=0 center dot 03) and tended to increase the frequency of circulating regulatory T cells (3 center dot 1 +/- 1cells/l at baseline, 7 center dot 7 +/- 2cells/l after third cycle). Rituximab also significantly decreased IL-15 trans-presentation on surface monocytes of patients negative for IL-15 serum (mean fluorescence intensity: 4 center dot 82 +/- 1 center dot 30 at baseline, 1 center dot 42 +/- 0 center dot 69 after third cycle P=0 center dot 05). Reduction of serum IL-15 was associated with decrease in CD8+CD45RO+/RA+ ratio (1 center dot 17 +/- 0 center dot 21 at baseline, 0 center dot 36 +/- 0 center dot 06 at third cycle, P=0 center dot 02). DAS28, erythrocyte sedimentation rate and C-reactive protein correlated significantly with CD8+CD45RO+/RA+ ratio (R=0 center dot 323, R=0 center dot 357, R=0 center dot 369 respectively, P

Introduction Adalimumab is a fully human anti–tumor necrosis factor α (anti-TNFα) monoclonal antibody that specifically blocks the interaction of TNFα with its receptors. It binds both soluble and transmembrane TNFα. We hypothesized that blocking these TNFα signals regulates the altered TNFα production in rheumatoid arthritis (RA) patients. Methods We compared, by flow cytometry, Toll-like receptor induction levels of membrane and intracellular TNFα in monocytes (iTNFα + CD14+ cells) from 12 patients before and after adalimumab treatment with those from 5 healthy donors. Results Before starting the treatment, the percentage of iTNFα+ CD14+ cells in the RA patients was significantly lower than that in healthy donors (mean ± SEM = 33.16 ± 4.82% vs 66.51 ± 2.4%, P

Platelet binding is a new regulatory mechanism of T cell function; higher frequency of platelet binding to lymphocytes is associated with low severe inflammatory profile. Expression of the scavenger receptor CD36 on lymphocytes is intriguing. We observed that a minor subpopulation of lymphocytes expressed CD36 on the cell surface. We investigated the source of CD36 and also the proliferation and cytokine production of these CD36(+) CD4(+) lymphocytes. Flow cytometry analysis and immunofluorescence microscopy showed that CD36(+) platelets were responsible for CD36 detection on lymphocytes. CD36 was then used as a tool to characterize lymphocytes with bound platelets. Activation-induced proliferation was lower in CD4(+) lymphocytes with bound platelets than lymphocytes without bound platelets. IL-17 and IFN- production was also reduced in lymphocytes with bound platelets. We then studied the presence of CD36(+) CD4(+) lymphocytes in RA patients. We observed that the percentage of CD4(+) lymphocytes with bound platelets was higher on RA patients than in healthy donors. RA patients with higher titers of anti-CCP, RF levels, and cardiovascular risk index presented a lower percentage of CD4(+) lymphocytes with bound platelets. These patients also had higher IL-17 and IFN- production. These results suggest that platelet-binding modifies lymphocyte function. This binding could be a regulatory mechanism in RA that confers a less severe phenotype.

Background Rheumatoid arthritis (RA) patients frequently report concomitant comorbidities that could worsen their prognosis. Tumour necrosis factor inhibitors (TNFi), the most common biological agents used, have shown efficacy in RA patients, although use in RA patients with certain comorbidities warrant caution (1). Abatacept, a biologic agent with a different mechanism of action, inhibiting the co-stimulation of T-lymphocyte, has demonstrated differentiated safety profile (2), that could influence the biological agent prescribed in RA patients with some associated comorbidities Objectives To analyse differences in the frequency of baseline comorbidities in RA patients treated with abatacept compared with those treated with TNFi Methods Patients with RA recruited into the BIOBADASER 2.0 register from January 2008 to December 2014 and treated with abatacept or TNFi with comorbidities were selected. Comorbidity was defined as ≥1 of the following at initiation of biological therapy: ischemic heart disease; malignancy (except lymphoma); diabetes; chronic pulmonary obstructive disease (CPOD); smoking; hypercholesterolemia; hypertension; heart failure; renal failure; lymphoma; osteoporosis; Epstein Barr, hepatitis B or C virus infection; and others. We analysed the frequency of each comorbidity, and differences in the rate of baseline comorbidities in the two groups were compared using t-test Results From January 2008 to December 2014, 640 and 252 RA patients treated respectively with TNFi or abatacept were included in the BIOBADASER 2.0 register, of whom 51.6% had ≥1 comorbidity at baseline. Frequencies for every basal comorbidity described are shown in Table 1. There was a significantly higher rate of heart failure in abatacept than in TNFi patients. Other comorbidities showed no significant differences. Conclusions RA patients treated with abatacept had a higher baseline rate of concomitant heart failure compared with patients treated with TNFi, probably reflecting different recommendations on biological use. Even though abatacept has demonstrated a differentiated safety profile, overall no differences in other baseline comorbidities were found between groups References Singh et al. Arthritis Rheum 2016;68:1–26. Singh et al. Cochrane Database Syst Rev. 2011;16:CD008794 Disclosure of Interest None declared

Background The prior GEMA (1) audit included patients before the EULAR 2006 recommendations were published (2), showing poor adherence to the EULAR recomendations in both crystal-based diagnosis and target urate levels. Objectives 1) assess the current quality of care in gout patients in Spain and 2) compare the current management with previous audit data. Methods The GEMA-II study included patients from EULAR 2006 to ACR 2012 guidelines. Agreement on diagnosis and treatment of gout with the EULAR 2006 recommendations was assessed. The selection of patient9s files for review was performed selecting a stratified 2-stage sampling of centers according to national population statistics. A random sample in each unit with a diagnosis code of gout (ICD, R9) was centrally selected. The sample size was estimated according to previous results and expected outcomes. The main co-principal variables were >50% improvement in the rate of gold-standard diagnosis and >50% improvement in the rate of patients at target serum urate levels. Results Data from 511 randomly selected clinical records from 38 units were included. Out of the 38 units, 93% reported having a polarized microscopy facility at the office. sUA at final visit was available in 479/511 (93.7%). Samples from the two audits (GEMA and GEMA-II) did not differ in age, sex distribution or time from onset to first visit. Crystal-based diagnosis was performed in 209/803 (26.0%) and 162/511 (31.7%) in the GEMA and GEMA-II studies (p=0,030, 5.7% improvement, not reaching endpoint >50%). By contrast, the pre-defined improvement >50% for the rate of patients achieving target serum urate ( 50% improvement (Table). Both crystal based diagnosis and rate of sUa in target were higher in Units with dedicated crystal-arthritis office and also in those that had presented the EULAR 2006 recommendations at least once. Conclusions Overall the improvement in the rate of patients achieving target serum urate over a 6-year period exceeded 50%. The rate of gold-standard diagnosis improved, but did not reach the expected outcome. Interest in recommendations and dedicated crystal arthritis offices were associated with best results. These preliminary data show for the first time that substantial improvement has been achieved in treat to target serum urate levels strategy for gout in the Rheumatology community. References Perez-Ruiz F, et al. J Clin rheumatol 2011. Zhang W, et al. Ann Rheum Dis 2006. Acknowledgement Funded by the Spanish Foundation for Rheumatology through an unrestricted grant from Menarini Spain Disclosure of Interest None declared

Objective.To investigate the response to therapy of entheseal abnormalities assessed with power Doppler (PD) ultrasound (US) in spondyloarthropathies (SpA).Methods.A total of 327 patients with active SpA who were starting anti-tumor necrosis factor (TNF) therapy were prospectively recruited at 35 Spanish centers. A PDUS examination of 14 peripheral entheses was performed by the same investigator in each center at baseline and at 6 months. The following elementary lesions were assessed at each enthesis (presence/absence): morphologic abnormalities (hypoechogenicity and/or thickening), entheseal calcific deposits, cortical abnormalities (bone erosion and/or proliferation), adjacent bursitis and intraenthesis and perienthesis (tendon body and/or bursa) PD signal. Response to therapy of each elementary lesion was assessed by calculating change in the cumulative presence from baseline to 6 months. Intraobserver reliability of PDUS was evaluated by blindly assessing the stored baseline images 3 months after the real-time examination.Results.Complete data were obtained on 197 patients who received anti-TNF therapy for 6 months. In 91.4% of the patients there were gray-scale or PD elementary lesions at baseline and at 6 months. Cumulative entheseal morphologic abnormalities, intraenthesis PD, perienthesis PD, and bursitis showed a significant decrease from baseline to 6 months (p < 0.05). There was high intraobserver reliability for all elementary lesions (interclass correlation coefficient > 0.90, p < 0.0005).Conclusion.Entheseal morphologic abnormalities, PD signal, and bursitis were US abnormalities that were responsive to anti-TNF therapy in SpA. PDUS can be a reproducible method for multicenter monitoring of therapeutic response in enthesitis of SpA.

Discussion and voting at OMERACT 9 confirmed 5 essential domains for outcomes of acute gout: pain, joint swelling, joint tenderness, patient global assessment and activity limitations. For studies in chronic gout 7 essential domains are: serum urate, acute gout attacks, tophus burden, health-related quality of life. activity limitations, pain, and patient global assessment. Implications of patient perspectives, discretionary domains for specific studies, measurement instruments and a possible responder index are under study. (J Rheumatol 2009:36:2342-5; doi: 10.3899/jrheum.090370)

Objectives: Ki-67 is expressed in the nuclei of dividing cells and can be used to assess proliferation of synovial inflammatory and stromal cells. We evaluated subintimal Ki-67+ cell density as a tissue biomarker for inflammatory arthropathies and compared it to subintimal CD68, a synovial biomarker of RA. Methods: Subintimal Ki-67+ and CD68+ cell densities were measured immunohistochemically in synovial specimens obtained from patients with rheumatoid arthritis (RA; n = 19), osteoarthritis (OA; n = 18), “non-inflammatory” orthopaedic arthropathies (avascular necrosis, meniscus injury, femur fracture; n = 16), chronic septic arthritis (n = 9), and histologically normal synovium (n = 10). Results were correlated with a histological synovitis score. Utilising the areas under receiver operating characteristic curves (AUCs), we compared the abilities of Ki-67 and CD68 to differentiate among these arthropathies. Results: Ki-67 was expressed widely in the subintima of inflamed specimens and in RA pannus invading hard tissues. Compared to normal controls, it was highly overexpressed in RA (26.6-fold) and chronic septic arthritis (55-fold), and mildly elevated in OA (3.9-fold) and orthopaedic arthropathies (2.1-fold). Ki-67 and CD68 differentiated similarly well between RA and OA (AUC: Ki-67 = 0.91, CD68 = 0.94), Ki-67 better between chronic septic arthritis and RA, and CD68 better between OA and normal controls. Ki-67 ( r = 0.80) and CD68 ( r = 0.79) correlated positively with the synovitis score. Conclusions: Subintimal Ki-67 was overexpressed in inflammatory arthropathies, distinguished among differentially inflamed arthropathies, and correlated positively with the histological severity of synovitis. It may prove useful in synovial tissue classification and as a synovial marker of disease activity in clinical trials when biopsies are available.

Objective An unexplained multisymptom illness, Gulf War veterans' illness (GWVI), has been described among allied force veterans of the first Gulf War (1990–1991). It has been proposed that some of its symptoms reflect an immune dysfunction, and rheumatologic symptoms including joint pain and stiffness are reported frequently. However, it is unknown whether synovial inflammation causes the articular symptoms. We examined synovial tissue from individuals with GWVI and joint pain for evidence of inflammation. Methods We compared synovial biopsy samples from 6 individuals with GWVI and joint pain with samples from 9 clinically asymptomatic controls (hematoxylin and eosin [H&E] stains only) and biopsy samples or surgically obtained specimens from 10 patients with rheumatoid arthritis (RA) and 12 with osteoarthritis (OA). Inflammatory changes were quantified in H&E stained sections with a modified synovitis score by immunostaining for CD3, CD20, CD38, CD68, Ki-67, and von Willebrand factor, and with a composite inflammation score based on these markers. Results Normal histology was seen in the GWVI specimens, except for mild focal lining hyperplasia and rare low-grade perivascular infiltrates in 1 specimen each. Mean ± SEM synovitis scores were lowest and nearly identical in control (1.38 ± 0.30) and GWVI specimens (1.41 ± 0.29), intermediate in OA specimens (2.64 ± 0.39), and highest in RA specimens (6.0 ± 0.19). Likewise, inflammatory cells, cell division, vascular density, and composite inflammation score were lowest in the GWVI specimens. Conclusion Despite significant joint pain, the GWVI synovia did not differ from normal controls. These results agree with other studies that have failed to document inflammatory or immunologic etiologies in GWVI.

Background Remission or low disease activity is the therapeutic target in the ACR-EULAR recommendation for the management of rheumatoid arthritis (RA). In multiple studies, musculoskeletal ultrasound (US) has shown to be more reliable and sensitive than physical examination in both the diagnosis and the assessment of RA activity. However, the real impact of this technique on routine daily care of RA and treatment decisions has not been studied. Objectives To assess the proportion of therapeutic decisions that are modified by the results of the US examination in patients with RA. To determine which group of patients would get more benefit from a musculoskeletal US to optimize treatment. Methods Seventy eight consecutive patients diagnosed with RA by ACR 1987 criteria and visited between July and November 2014, were included. All patients were initially visited by their usual rheumatologist and a therapeutic decision was made according to physical examination and clinical and laboratory findings. Subsequently, a musculoskeletal US was performed by an expert sonographer of our center and the usual rheumatologist was asked to reassess his therapeutic decision in light of the US findings. We classified the change in the therapeutic attitude as: negative (maintenance of therapeutic attitude) and positive (increase or reduction in treatment, compared to the initial decision). Demographic, clinical and laboratory data were collected from the clinical history and activity scores were calculated. Results Clinical, demographic, laboratory, treatment and activity score data are shown in table below. In 29 patients [37.2% (95% CI 26.5 to 48.9)] the findings in the US examination conditioned a change in the therapeutic decision of the usual rheumatologist. In 18 patients (62.07%) the change was towards an intensification of treatment, while in 11 patients (37.93%) a decrease was possible. Change of treatment was more frequent in patients with intermediate disease activity (mild and moderate activity) than in those with extreme activities (remission and high activity), 41.4% vs 25%, although this difference was not statistically significant. A higher frequency of change was found in men (53.8% vs 33.8%) and erosive RA forms (43.6% vs 21.7%), but the results did not reach statistical significance. Conclusions Musculoskeletal ultrasound, when added to routine rheumatologic investigation, is an important tool for treatment decisions in the routine daily care of rheumatoid arthritis. Patients with intermediate activities of the disease might get more benefit from the use of an US examination. Disclosure of Interest None declared

Background There are few data about Tocilizumab (TCZ) in monotherapy effectiveness in clinical practice conditions Objectives To analyze the effectiveness TCZ monotherapy at medium/long term in clinical practice Methods Observational, retrospective, multicenter, 2-year study of RA patients on TCZ monotherapy.We recorded: demographic and clinical data (duration of RA, RF and CCP antibodies, previous treatments and reason for its discontinuation); At baseline and at 3, 6, 9, 12, 18 and 24 months:RA activity (DAS-28 ESR index, TJC, SJC, ESR, CRP and % of patients in Remission or Low Disease Activity (LDA). Adverse effects were also recorded Results 123 patients were included, with a mean age of 57.7±12.5 years and 85.4% females. Mean disease duration of 14.4±12.0 y; 67.5% and 5993% were RF and anti-CCP positive. 98.4% had previously received conventional DMARD (2 DMARDs: 30.9% and ≥3 DMARDs: 38.2%), reasons for DMARD discontinuation were inefficacy (26%), adverse events (58.5), patient decision (8.9%) and other reasons (4.1%). 13% had not received prior biological DMARDs; 34.1% had received 1; 20.3% 2; 16.3% 3; 8.9% 4 and 6.5% ≥5) A relationship between Remission/LDA and disease duration and reason for discontinuation of prior conventional DMARD was not found. An association among the number of previous biological treatments and a low disease activity at 6 m (p Conclusions In our experience, TCZ monotherapy is effective at medium/long term regardless of the duration of the disease and previous treatments, maintaining a high retention rate Disclosure of Interest None declared

Background Macrophages initiate the inflammatory response to monosodium urate (MSU) crystals and produce inflammatory cytokines and chemokines that induce migration of blood monocytes to further amplify the inflammatory response. One of the questions that remain unanswered is why some patients with hyperuricemia, and even with MSU deposits, remain clinically asymptomatic. Different subpopulations of blood monocytes have been recognised: classical (CD14++CD16-), intermediate (CD14++CD16+) and non-classical (CD14+CD16++); characteristically intermediate monocytes are expanded in infectious and inflammatory diseases and are associated with atherosclerosis. [1][2] Objectives To investigate the possibility that inflammasome reactivity to MSU crystals could influence the clinical expression of gout and to analyse the distribution of monocyte subpopulations in patients with gout. Methods 17 patients with gout (13 asymptomatic and 4 during an acute flare) and 19 healthy controls were selected. Inflammasome activation after stimulation with MSU (200 μg/ml), ATP (5mM) and nigericin (20 μg/mL) was assessed in peripheral blood mononuclear cells (PBMCs) by flow cytometry using Caspase-1 FLICA™ Detection Kit (Immunochemistry Technologies). Phagocytosis of MSU crystals was quantified by flow cytometry. PBMCs were cultured for 24 hours in the presence of MSU (200 μg/ml), LPS (100 ng/ml) or both and IL-1β was quantified by ELISA. Samples of peripheral blood were stained with CD45, HLA-DR, CD16, and CD14 antibodies. Uric acid, creatinine and C-reactive protein (CRP) were quantified in sera. Flow cytometry and statistics analysis were performed with the FACSDiva and GraphPad Prism 5. Results No differences were observed in active caspase-1 at baseline. However, when stimulated with MSU, monocytes from gout patients exhibited a higher increase of active caspase-1 (mean ± SEM, gout 2.20±0.15, controls 1.66±0.18, p=0.0419). Differences in phagocytosis of MSU crystals were excluded, as in both groups monocytes exhibited equivalent phagocytic capability. Unexpectedly, PBMCs of patients with gout exhibited diminished IL-1β production when challenged with LPS and MSU (p=0.0473). Regarding monocyte subpopulations, the intermediate phenotype was expanded in patients with gout during an acute flare and a weak correlation between intermediate monocytes and CRP was observed. Conclusions Monocytes of patients with gout exhibit an enhanced inflammasome activation with MSU crystals, suggesting that a reduced threshold in the inflammatory response could be involved in the development of clinical gout. However, for unknown reasons they produced less IL-1β upon stimulation. The expansion of intermediate monocytes was observed during gout flares and, although it cannot be excluded that intermediate monocytes could be “innocent bystanders” in the context of inflammation, it could suggest that these monocytes participate in the inflammatory response to MSU crystals. References Heine G. Nat Rev Nephrol 2012;8(6):362-9. Rossol M. Arthritis Rheum 2012;64(3):671-7. Disclosure of Interest None declared

Background Recent studies in the field of axial spondyloarthropathies (SpA-ax) have shown a group of patients with chronic lower back pain without evidence of radiographic damage (non-radiographic axial spondyloarthritis). Currently, data is lacking that would confirm whether it is an early stage of the disease or a group of SpA-ax that is different, in which time of progression and radiographic damage show no relationship. Objectives Describe our cohort of patients diagnosed with radiographic axial spondyloarthritis. Assess whether those with both sacroiliac and spinal radiographic involvement have a longer duration of the disease and the relationship between this most-affected group and the different items that constitute the ASAS criteria for SpA-ax. Methods All patients diagnosed with SpA-ax by ASAS or NY criteria, who were seen in a monographic consultation of spondyloarthritis of our center between January 2012 and December 2013, were reviewed. Only those with sacroiliitis of grade II or higher were included; patients who did not have spinal radiographs were excluded. The following clinical and laboratory variables were collected from clinical history: age, sex, duration of disease, inflammatory back pain, arthritis, enthesitis, uveitis, dactylitis, psoriasis, inflammatory bowel disease, positive response to NSAIDs, family history of SpA, HLA-B27 and elevated CRP. The presence of 3 or more syndesmophytes in the dorsal and/or lumbar region was considered as spinal involvement. For statistical analysis, student9s t-test, chi-square test or Fisher9s exact test were performed where applicable. Results Of the 72 patients diagnosed with SpA-ax, 58 met the inclusion and exclusion criteria. The mean age of the study patients was 53.69 years and 69% were men. The mean disease duration was 19.48 years and 36 patients had spinal involvement. Only the age of patients, the sex and the duration of the disease showed significant results regarding the structural damage (see table). Conclusions In our cohort, patients with more severe radiographic involvement were those of a longer disease duration and an older age, with a predominance of men. No significant differences for the remaining assessed variables were found, including signs of inflammation and HLA-B27, which were similar in both groups of patients. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4483

Systemic-onset juvenile idiopathic arthritis (SOJIA), formerly called Still’s disease, is a subset of juvenile arthritis that describes patients with fever, rash, arthritis, serositis and visceromegaly. In up to 30% of cases the disease has a chronic course and management requires high doses of glucocorticoids, disease-modifying antirheumatic drugs (DMARD), tumour necrosis factor alpha (TNFα) inhibitors or anakinra.1–6 However, this therapeutic arsenal is unable to control the disease in all patients. Recently, rituximab, a chimeric anti-CD20 monoclonal antibody, has been successfully used in two patients with refractory adult-onset Still’s disease.7 As the similarity of clinical and laboratory features present in SOJIA and adult-onset Still’s disease implies that these conditions have similar …

Background Systemic sclerosis or scleroderma (SSc) is a connective tissue disease which frequently presents lung affectation, being the principal cause of death in these patients. Currently, only cyclophosphamide (CyC) has shown efficiency to treat this complication. However, this efficiency is modest and not kept through the time. Several medicines have been tested for the treatment of this complication with controversial results. Rituximab (RTX) seems to show improvement in patients with SSc and Interstitial Lung Disease (ILD) refractory to others treatments, but there are not pivotal assays in this regard and the experience is limited. Objectives To study the evolution of Pulmonary Function Test (PFT) in patients with SSc affected by ILD refractory to usual treatment and have made at least one cycle of Rituximab. Methods Multicenter observational prospective study in patients with ILD-SSc was performed. These patients had one cycle of two Rituximab infusions for ILD and previously had realized CyC, azathioprine or mycophenolic acid with treatment failure. We evaluated the following data: gender, age, onset age of Raynaud’s phenomenon, age at diagnosis of SSc, age at diagnosis of ILD, ILD type, total dose of CYC, use of concomitants steroids, and other immunosuppressive agents. PFT outcome after each therapy and after 4 months of treatment with RTX was included. Results We collected the data of four patients who realized one complete cycle of treatment with RTX. Patients were women and presented diffuse cutaneous shape with antitopoisomerase I antibodies. The radiologic affectation was Non-Specific Interstitial Pneumonia (NSIP) in all cases. Patient’s characteristics are showed in table 1. The patient who presented the best response to RTX (Patient 4) had the highest dose of CyC accumulated previously. As a whole, patients presented a worsening of the predicted value of FVC and DLCO after treatment with CyC. Four months later of RTX infusion, we did not observe any worsening in the values of FVC beside of a trend to improve the values of DLCO. The best response in concern to respiratory function parameters was not related with taking concomitant or accumulated dose of other drugs different to CYC. Conclusions Rituximab could be an alternative to the treatment and stabilization for interstitial lung disease in patients with SSc, however experience remains limited. Disclosure of Interest None Declared

Objectives To determine the relation between different pathological capillaroscopic findings and pulmonary function tests in patients with scleroderma. Methods Retrospective observational study of a cohort of patients with systemic sclerosis (SSc) or early SSc (eSSc) followed in Rheumatology Unit of a University Hospital from 1975 to 2011. Patients who had a nailfold videocapillaroscopy with 120x magnification were selected. The following pathological findings were considered: presence of megacapillaries and/or angiogenesis and loss of capillary density. Capillaroscopic findings were compared with the following values of lung function tests performed in the same year of the capillaroscopy: % predicted forced vital capacity (FVC), DLCO and the FVC/DLCO ratio. The following variables were also included: sex, type of SSc, presence of digital ulcers, interstitial lung disease (ILD), scleroderma renal crisis (SRC) and pulmonary hypertension determined by echocardiogram. Statistical analysis was performed by T Test to compare the capillaroscopic findings and pulmonary function test. Values of p Results Of all patients (n=136), 84 had at least one videocapillaroscopy. We observed that 92,9% were female, 67% (57/84) had limited SSc, 25,3% (21/84) ILD, 29,8% (25/84) DU and 17,9% (15/84) of patients had PH. We analyzed the capillaroscopics findings with the lung function parameters. We found that patients with loss of capillary density had worse FVC (87% ± 19,58 vs 101,12% ± 16,06, p p Conclusions Patients with significant loss of capillary density in the nail-fold capillaroscopy showed worst values of FVC and DLCO. Prospective studies are needed to determine if the nail-fold capillaroscopy may be useful to study lung involvement in patients with systemic sclerosis. Disclosure of Interest None Declared

Background Renal biopsy is an essential tool in lupus nephritis (LN) diagnose, It is also useful to establish prognosis. In general biological markers as complement, Anti ADN autoantibody are used to determine lupus clinical activity and to predict risk to have a renal flare. However, the literature reports a low sensitivity (50-70%) and specificity ( Objectives To study silent lupus nephritis (SLN) frequency in protocol renal biopsy made 2 years after clinical complete remission. Methods A retrospective and descriptive study was performed. The population comprised patients diagnosed with LN that, after a course of treatment, accomplished clinical criteria for complete remission (defined as: urine protein/creatinine ratio Diagnostic criteria for SLN were: renal histology compatible with type II, III, IV, V and VI in renal biopsy and clinical criteria for complete remission. Results Nine patients, 7 women and 2 men with a mean age of 24.2 years (at renal flare time) were included. SLEDAI mean was 12.6, 2 were on treatment with Mycofenolate (MYC), 1 was on hydroxychloroquine (HCQ), 1 on Azatioprine (AZA), 1 on Lefluonomide and 4 were not on any treatment. First biopsy results were: 5 patients had Type IV, 2 patients had type II, 1 patient had type III+V and 1 patient had II+V. Activity index was 4 and chronicity index was 1.77. All patients reached complete remission after treatment (cyclophosphamide (CYC) 7, AZA 1 and the last with Rituximab, all of then receive prednisone and maintenance therapy with MYC). Protocol biopsy was performed at a mean time of 24 month after treatment, 6 patients improved histology, in 2 patients no changes were found and 1 patient worsen (table 1). Activity index improved from 4 to 0.44 and chronicity from 1.77 to 1.55. All patients met NSL clinical criteria at the time of protocol biopsy. Conclusions NLS is an underdiagnosed entity in patients with SLE. Renal biopsy remains as the gold standard for diagnosis. Although larger studies are required, our study supports that protocol biopsies, once clinical remission is reached, are needed to determine histological remission. References Diaz MM, Ballarin J. Nefropatia lupica silente. Semin Fund Esp Reumatol. 2012. doi:10.1016/j.semreu.2011.10.002. Zabaleta-Lanz M, Vargas-Arenas RE, Tapanes F, Daboin I, Pinto JA, Bianco NE. Silent Nephritis in systemic lupus erythematosus. Lupus. 2003, 12:26-30. Weening J, D’Agati V, Schwartz M, Seshan S, Alpers C, Appel G, et al., on behalf of the ISN, RPS Working. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol. 2004;15:241–50. Disclosure of Interest None Declared

Background Tocilizumab is a humanized monoclonal antibody that blocks IL-6 mediated pro-inflammatory signalling in rheumatoid arthritis patients. The safety profile of tocilizumab has been extensively evaluated in clinical trials. However, there is little data on markers at the initiation of tocilizumab therapy that may predict the development of adverse effects requiring drug withdrawal. Objectives To identify markers that predict the development of secondary effects that required drug withdrawal the 6 first months after initiating tocilizumab therapy. Methods Forty-six rheumatoid arthritis patients treated with tocilizumab in routine clinical practice were retrospectively evaluated 24 weeks after initiating therapy. Demographic and clinical data, complete blood cell counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), titers of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies, serum cytokines (IL-6, IL-15 and IL-17) and the frequency of activated CD4+, CD8+ and Treg cells were collected before tocilizumab administration (baseline). Characteristics of patients with and without adverse effects were compared. Results Twelve (26.1%) patients developed adverse effects that required drug withdrawal during the first six months of tocilizumab therapy. Seven patients suffered an allergic or infusional reaction and two patients had neutropenia. All recovered after drug withdrawal. Two further patients suffered an infection requiring hospitalization (salpingitis and periappendiceal abscess) and one patient had a myocardial infarction. Patients with and without adverse effects had comparable ages and disease evolution. Patients with adverse effects had lower neutrophil counts (4.1±2.6 vs 5.6±1.8, p There were no differences in the frequency of T cell subsets and Tregs between patients with and without adverse effects before the treatment. Conclusions Patients with adverse effects presented fewer prognostic markers of severe disease. Higher levels of some markers (CRP, anti-CCP antibodies, IL-6, IL-15 and neutrophil counts) may identify patients less likely to suffer adverse effects due to tocilizumab therapy. Disclosure of Interest None Declared

Background Identifying predictors of response to biological agents is important for both the individual patient and health economics. There is data about several predictors of rituximab response, like a positive anti-CCP or rheumatoid factor, a low number of preplasma cells or lymphocites or an IgG level above normal.Defining response in rituximab treated patients can be complex. If we consider to measure the response to rituximab after three months, those patients with slow response will be missed. Otherwise, if we consider to measure it after six months, those ones that respond early but relapse before six months, will be also missed. Nowadays with all the current therapeutic targets, we should expect to achieve a early and maintained response. We therefore decided to consider as responders those patients that achieved a moderate/good Eular response at three and six months. Objectives To determinate new predictors of an early and mantained response to rituximab in rheumatoid arthritis pacients. Methods Prospective study of twenty seven consecutive rheumatoid arthritis patients, that failed to anti-TNF therapy, and were treated with rituximab (2 x 1g, two weeks apart). Demographic, clinical and laboratory data was obtained. According to our response criteria, we determined the percentage of patients who achieved an Eular response at three and six months. We then compared the baseline characteristics between early and maintained response patients (E&M-R) and the remaining patients (P). Results Baseline characteristics: mean age was 60.2±11.2 years, 92.6% were women, RA years of evolution were 16.2 (2-35), 96.3% were seropositive (RF and/or anti-CCP), 44.4% had a history of rheumatoid nodules, 88% had an erosive RA, previous DMARDs were 3.1±1.3, previous anti-TNF were 1.45 (1-3) and DAS28 was 5.8±0.87. When comparing the clinical characteristics of E&F-R and P groups, similar DAS28 was observed. The analysis of the laboratory parameters is shown in Table. Conclusions High absolute numbers of CD19+ cells and low IgM levels at baseline were statistically associated with an early and maintained response to rituximab. These parameters could therefore be used as predictor markers of the response. Disclosure of Interest None Declared

Background New data indicates that Tocilizumab (TCZ) plus Methotrexate (MTX) does not have superior clinical efficacy to TCZ alone. Objectives To evaluate demographic and clinical features of a cohort of patients with rheumatoid arthritis (RA) treated with TCZ monotherapy in the clinical practice Methods Demographic and clinical data of 81 patients treated with TCZ monotherapy were assessed in 7 Spanish centers. Duration of RA, previous treatments, reason for DMARDs discontinuation and adverse events were included. Clinical activity assessed by Disease Activity Score (DAS) 28-ESR index, and laboratory data were done at weeks 0, 12 and 24 (W0, W12 and W24). Statistical analysis was performed using T-Student and Wilcoxon Tests Results A total of 81 patients were evaluated. Mean age: 57.7±12.7 years and 81.2% females. At baseline, patients had mean disease duration of 13.2±9.4 years. 69.1% and 58.0% were Rheumatoid Factor and anti-CCP positive. Patients had been treated previously with Methotrexate (82.1%), Leflunomide (50.0%), hydroxycloroquine (21.8%), Gold Salts (16.7%), Cyclosporine (11.5%) and Salazopyrine (7.5%). Reasons for DMARD discontinuation previous TCZ monotherapy were: adverse effects 59.2%, inefficacy 26.3% and patient decision 7.9%. Patients had been treated with 3 (16.0%), 2 (21.0%) and 1 (30.9%) biological therapies before starting TCZ. TCZ was the first biological therapy in 12.3% of patients. Biological treatments previous TCZ were Etanercept (64.7%), Adalimumab (52.9%), Infliximab (47.1%), Rituximab (32.4%), Abatacept (25.0%) and Anakinra (5.9%). The mean (±SD) CRP, ESR, DAS28, SJC and TJC at W0 were 10.2±17.3 mg/dl, 41.9±31.4, 5.7±1.4, 7.7±6.9 and 11.0±7.6 respectively. At W12 and W24, 29.0% (n=18/62), 42.1% (n=24/57) of patients achieved DAS28 remission criteria and 46.8% (n=29/62), 59.6% (n=34/57) low disease activity respectively. We find a relationship between disease duration and the probability to achieve the remission at W12: T-test for equality of means: 15.2 (group no-remission) vs 10.1 years (group of remission), p=0.046. We also find relationship between the number of previous biological therapies and the probability to achieve the low disease activity at W12. T-test: 2.6 (group no-low disease activity) vs 1.7 (group of low disease activity), p=0.023. This relationship disappeared at W24 in both cases Conclusions Our series of RA patients show the efficacy of Tocilizumab treatment administered as monotherapy in clinical practice. The main reason for using Tocilizumab monotherapy has been intolerance to DMARDs Disclosure of Interest B. Magallares: None Declared, E. Quesada: None Declared, M. P. Lisbona: None Declared, J. Calvet: None Declared, R. Sanmarti Consultant for: Roche, D. Reina: None Declared, J. Narvaez: None Declared, C. Diaz-Torne: None Declared, S. Marsal: None Declared, J. Maymo: None Declared, M. Garcia-Manrique: None Declared, M. Moreno: None Declared, V. Hernandez: None Declared, H. Corominas Consultant for: Roche, J. M. Nolla Consultant for: Roche