Nora Ng

Angiogenic gene expression and vascular density are reflected in ultrasonographic features of synovitis in early rheumatoid arthritis: an observational study

IntroductionNeovascularization contributes to the development of sustained synovial inflammation in the early stages of Rheumatoid Arthritis. Ultrasound (US) provides an indirect method of assessing synovial blood flow and has been shown to correlate with clinical disease activity in patients with Rheumatoid Arthritis. This study examines the relationship of US determined synovitis with synovial vascularity, angiogenic / lymphangiogenic factors and cellular mediators of inflammation in a cohort of patients with early Rheumatoid Arthritis (RA) patients prior to therapeutic intervention with disease modifying therapy or corticosteroids.MethodsAn ultrasound guided synovial biopsy of the supra-patella pouch was performed in 12 patients with early RA prior to treatment. Clinical, US and biochemical assessments were undertaken prior to the procedure. Ultrasound images and histological samples were obtained from the supra-patella pouch. Histological samples were stained for Factor VIII and a-SMA (a-smooth muscle actin). Using digital imaging analysis a vascular area score was recorded. QT-PCR (quantitative-PCR) of samples provided quantification of angiogenic and lymphangiogenic gene expression and immunohistochemistry stained tissue was scored for macrophage, T cell and B cell infiltration using an existing semi-quantitative score.ResultsPower Doppler showed a good correlation with histological vascular area (Spearman r - 0.73) and angiogenic factors such as vascular endothelial growth factor- A (VEGF-A), Angiopoietin 2 and Tie-2. In addition, lymphangiogenic factors such as VEGF-C and VEGF-R3 correlated well with US assessment of synovitis. A significant correlation was also found between power Doppler and synovial thickness, pro-inflammatory cytokines and sub-lining macrophage infiltrate. Within the supra-patella pouch there was no significant difference in US findings, gene expression or inflammatory cell infiltrate between any regions of synovium biopsied.ConclusionUltrasound assessment of synovial tissue faithfully reflects synovial vascularity. Both grey scale and power Doppler synovitis in early RA patients correlate with a pro-angiogenic and lymphangiogenic gene expression profile. In early RA both grey scale and power Doppler synovitis are associated with a pro-inflammatory cellular and cytokine profile providing considerable validity in its use as an objective assessment of synovial inflammation in clinical practice.

Use of ultrasound-guided small joint biopsy to evaluate the histopathologic response to rheumatoid arthritis therapy: recommendations for application to clinical trials.

To examine in a cohort of rheumatoid arthritis (RA) patients undergoing serial ultrasound (US)–guided biopsies of small joints in the context of clinical trials whether sufficient synovial tissue could be obtained at both baseline and second biopsy to: 1) accurately evaluate the synovial immune phenotype, 2) permit adequate RNA extraction to determine molecular signatures, and 3) sensitively detect change in the number of synovial sublining macrophages (CD68+) following effective therapy.

THU0087 Synovial Ectopic Lymphoid-like Structures are Associated with Diagnosis of Rheumatoid Arthritis, Disease Activity and Antibody Status in Early Arthritis Patients

Background The presence of ectopic lymphoid-like structures (ELS) within the synovial tissue of a cohort of patients with inflammatory arthritis is well recognised. There is also data supporting the concept that these structures are immunologically competent and can support chronic inflammation within the joint. There is limited data however examining whether the presence of ELS associates with specific clinical phenotypes in early arthritis. Objectives The aim of this study was therefore to investigate whether synovial ELS associated with specific clinical phenotypes in an early arthritis cohort. Methods A cohort of DMARD-naïve early arthritis (<12 months duration, at least 1 swollen joint) patients recruited at Barts and The London Hospital, as part of the MRC-funded Pathobiology of Early Arthritis Cohort (PEAC) http://www.peac-mrc.mds.qmul.ac.uk/ were included in the analysis. The study was approved by the ethics committee (REC). Baseline disease characteristics assessed included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, rheumatoid factor (RF), anti-cyclic-citrullinated peptide antibodies (anti-CCP) and 28 joint-disease activity score (DAS28). All patients underwent ultrasound-guided synovial biopsy of an affected joint at baseline. Sections of paraffin embedded RA synovial tissue were stained with standard Haematoxylin and Eosin (H&E) and graded as either a diffuse or aggregate synovitis. In addition sequentially cut paraffin sections underwent immunohistochemical staining for B-cells(CD20), T cells (CD3) and macrophages(CD68) and were semi-quantitatively scored (0-4) for each marker. Results 84 sequentially recruited patients with both synovial tissue and a complete clinical data set were included within the analysis (61% female, mean age 50). 64% (n=57) of patients were classified as diffuse and 36% (n=27) as aggregate. The presence of synovial lymphocytic aggregates was significantly associated with higher synovial infiltration of T cells, B cells, plasma cells and both lining and sublining macrophages (p<0.001). Moreover, the presence of synovial aggregates was significantly associated with baseline RA diagnosis (1987 ACR criteria), positive ESR/CRP and seropositivity for RF and anti-CCP antibodies. Interestingly, there was also a significant correlation between a higher synovial infiltration of B cells and plasma cells and positivity for anti-CCP antibodies (p=0.002 and p<0.001) and RF (p<0.001 and p<0.001) in the serum. Conclusions The significant association of synovial ELS with the diagnosis of RA and sero-positivity for RF and anti-CCP antibodies in early arthritis stronlgly supports the concept that these structures are functional and involved in disease pathogenesis. In addition these observations also suggest that baseline synovial pathotype may have a role as a prognostic biomarker in early arthritis. Disclosure of Interest None Declared

OP0240 Synovial Lymphocytic Aggregates Associate with Highly Active RA and Predict Erosive Disease Progression at 12 Months: Results from The Pathobiology of Early Arthritis Cohort

Background The synovial cellular infiltrate in RA has for some time been recognised to organise into lymphocytic aggregates with a number observations suggesting they are immunologically competent and can support chronic inflammation. However, their clinical significance has been controversial with conflicting publications reporting diverse associations with disease outcome. Objectives The aim of this study was to examine in a cohort of therapy naïve, early RA patients whether baseline synovial pathotype: i)associated with specific clinical phenotypes, ii)predicted response to DMARD therapy, and iii)predicted joint damage progression Methods 135 DMARD-naïve early RA patients were recruited as part of the Pathobiology of Early Arthritis Cohort at Barts Health NHS Trust. Following pre-treatment synovial biopsy clinical data was collected at baseline and 12 months. Following immunohistochemical staining the degree of synovial infiltration by CD20+B cells, CD3+T cells, CD68+macrophages and CD138+plasma cells was determined. Patients were then categorised into synovial pathotypes: lymphoid, myeloid or fibroid according to the degree of immune cell infiltration. Samples also underwent nanostring analysis of 238 genes. Significant differences in clinical parameters at baseline and progression in radiographic damage at 12 months between synovial pathotypes was determined. Results At baseline a lymphoid pathotype significantly associated with ACPA+ve (0.017) and highly active disease (DAS28, CRP, ESR and swollen joint count, p<0.01). Furthermore a significantly higher number of patients with a baseline lymphoid pathotype (vs myeloid/fibroid) developed radiographic progression (9/26 vs 5/53, p=0.026). A cohort of 79 genes were identifed from the nanostring analysis that were differentially upregulated in patients with joint damage progression. Logistic regression analysis was used to develop a clinical model for predicting radiographic progression (final model ESR, RF and ACPA) with an AUC of 0.86. Integration of synovial gene expression profiles into the clinical model improved the AUC to 0.96. Conclusions The demonstration in this early RA cohort of a significant association between a lymphoid pathotype and a severe clinical phenotype/sero positivity for ACPA supports a direct role for synovial lymphoid structures in disease pathogenesis. Furthermore patients with a lymphoid pathotype were significantly more likely to develop radiographic damage. Integration of synovial gene expression profiles into a clinical model of radiographic progression enhanced performance. This data strongly supports a role for integration of synovial biomarkers into clinical prediction models of radiographic progression in early RA with critical implications for future patient stratification. Disclosure of Interest None declared

OP0263 Synovial B-Cell Gene Signature Predicts Response To Rituximab Therapy

Background Predicting response to biologic therapies in RA remains a clinical challenge. The anti-CD20 monoclonal antibody Rituximab effectively depletes peripheral blood B-cells, however response rates are approximately 60%. We hypothesized that expression of CD20 in diseased tissue may be an important predictor of response, since up to 40% of patients have few/no B-cells present in the synovium. Objectives To ascertain whether a synovial B-cell gene signature can enhance prediction of responsiveness to Rituximab therapy and identify genes involved in response/non-response to treatment. Methods Synovial tissue was obtained using ultrasound-guided synovial biopsies from 20 patients with active RA who were treated with Rituximab therapy after failure of conventional DMARD and anti-TNF therapy. High-throughput quantitative real-time PCR for 190 genes was performed in collaboration with MedImmune (MedImmune, LLC) using the Fluidigm platform. Samples were classified as B-cell “rich” or “poor” according to levels of MS4A1 expression. Using an empirical Bayes statistical model, a further 17 significant (p<0.05) genes were identified to create a baseline B-cell gene expression signature. Hierarchical clustering and receiver operating characteristic curve analysis was used to assess ability to predict EULAR criteria response at 16 weeks. Gene expression was compared pre- and post-treatment in responders versus non-responders and correlated with delta DAS-28. Logistic regression with backward and forward selections using AIC was applied to identify further predictive models. Results Seventeen genes were identified that clustered with MS4A1 expression to create the B-cell signature. Fifteen of these are directly involved in B-cell and plasma-cell signaling or differentiation pathways and immunoglobulin synthesis. Two genes identified within this signature play a pivotal role in antigen presentation and TH17 differentiation. The baseline B-cell signature had an area under ROC curve (AUC) of 0.87 (95%CI 0.76–1.0) to predict response to Rituximab therapy at 16 weeks. Three additional genes were identified segregating responders from non-responders; that when combined with the baseline B-cell signature the AUC improved to 0.95. Additionally, ten genes were identified that significantly correlated with delta DAS-28. High expression of genes involved in the formation of ectopic lymphoid structures and the TH17 lineage correlated with non-response to Rituximab therapy (all p<0.05). Conclusions This study shows that a B-cell rich gene signature has high sensitivity to predict response to Rituximab therapy. High expression of TH17 related genes correlates with non-response to B-cell depletion, indicating that in a subset of patients, these pathways may play a more pivotal role in disease pathogenesis. The observed high expression of ELS associated genes in non-response may relate to variable synovial B-cell depletion; disruption of these follicles may be the key to response, particularly with repeat cycles. These findings warrant confirmation in a larger cohort of patients; however they strongly support the notion that a stratified approach to treatment relies upon the identification of biomarkers, both in the synovium and peripheral blood that reflect heterogenous molecular disease pathways in RA. Disclosure of Interest None declared

SAT0048 Synovial Lymphocytic Aggregates Predict Clinical Response to Certolizumab Pegol in Rheumatoid Arthritis (Clinical and Pathological Response to Certolizumab-Pegol (Clip-Cert) Study)

Background The identification of biomarkers of clinical outcome to guide therapeutic decisions in rheumatoid arthritis (RA) would bring major benefits to patients and considerable health-economic value. There is data suggesting that response to TNF alpha inhibitors (TNFi) in RA may partly be explained by modulation of synovial ectopic lymphocytic aggregates (ELN) within the synovial tissue, although this is still controversial. Certolizumab pegol is a pegylated fully humanized TNFi. Whether specific synovial pathotypes predict response to the drug is unknown. Objectives The aim of this study was to investigate whether the presence of synovial ELN at baseline predicts clinical response to treatment with certolizumab pegol in RA patients. Methods 25 biologic-naïve RA patients who qualified for TNFi therapy according to NICE guidance (National Institute for Health and Clinical Excellence, http://guidance.nice.org.uk/TA186) was recruited at Barts and the London Hospital. Patients underwent ultrasound guided synovial biopsy of an active joint prior to commencing therapy with certolizumab pegol. Following 3 months of therapy, response to treatment was assessed according to EULAR response criteria. Paraffin embedding sequentially cut sections of synovial tissue underwent H&E staining and immunohistochemical staining for CD20 to detect B cells. Sections were graded as either diffuse or aggregate infiltrate as previously described [Manzo, Eur J Immunol 2005]. The study received local ethics approval. Results Characteristics of patients at baseline and clinical outcome after 3 months of therapy with comparison between ELN- and ELN+ are shown in Table 1 (Chi square or Mann Whitney test, as appropriate) Table 1 All (25=100%) ELN− (14=56%) ELN+ (11=44%) P value Baseline  Female, % 18 (72%) 10 (71%) 8 (72%) 0.94  Age, mean ± SD 51±12 52±12 50±13 0.45  Dis dur (yrs), mean ± SD 6±5 7±6 5±4 0.97  ESR, mean ± SD 26±18 23±18 30±18 0.26  CRP, mean ± SD 10±24 4±3 18±35 0.04  IgM RF, % 13 (52%) 7 (50%) 6 (54%) 0.82  CCP, % 16 (64%) 9 (64%) 7 (63%) 0.97  DAS28, mean ± SD 6.3±0.7 6.3±0.8 6.3±0.7 0.74  HAQ, mean ± SD 1.57±0.71 1.75±0.65 1.35±0.75 0.15  Erosive, % 10 (40%) 5 (35%) 5 (45%) 0.62 Post treatment  DAS28, mean ± SD 4.1±1.4 4.7±1.5 3.3±0.9 0.01  Delta DAS28, mean ± SD 2.2±1.2 1.6±1.3 3.0±0.8 0.003  EULAR response, % 18 (72%) 7 (50%) 11 (100%) 0.006 Presence of ELN+ is strongly associated with a significant post- treatment lower DAS28 (0.01) and conversely significant higher Delta DAS28 (0.003) as well as good/moderate EULAR response. A stepwise logistic regression analysis was performed by entering several baseline variables: gender, age, disease duration, presence of erosions, RF and CCP status, use of steroids, DAS28, HAQ, presence of ELN. Only presence of ELN was identified as a potential predictor of EULAR response (Fisher exact test p<0.001; Logistic Regression OR=11.0, 95% CI=1.10-109.67, p=0.041). Conclusions Our findings strenghts the relevance of synovial pathotype in relationship with clinical outcome. In particular, the presence of ELN may be a potential predictor of primary clinical response to certolizumab pegol treatment, in line with previous data observed for other TNFi. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5564

OP0032 Baseline Synovial B-Cell Status Predicts Response to Rituximab Therapy in RA

Background B-cells are key mediators in RA pathogenesis through the initiation of several pathways that lead to the perturbation of the immune system. Rituximab, an anti-CD20 monoclonal antibody is recommended for use after failure with traditional disease modifying agents and anti-TNF therapy. Despite using peripheral blood B-cells as a marker to ensure depletion, the clinical response to Rituximab remains variable, highlighting an unmet need for further biomarkers of response. Mechanisms that underpin the variation in clinical outcome are yet to be fully elucidated but may relate to distinct differences in cellular infiltrate and target expression within the synovium. Objectives The aim of this open-labelled pilot study was to test the hypothesis that patients with a B-cell rich versus B-cell poor synovial pathotype have an enhanced response to B-cell depletion following therapy with Rituximab. Methods Synovial biopsy (Ultrasound guided n=34, arthroscopic n=6) was performed at baseline in 40 patients with active RA (as defined by a DAS-28 score of >5.1) who had failed treatment with standard disease modifying therapy. 35 patients had received prior anti-TNF therapy, a subset of 5 patients were anti-TNF naïve. Rituximab was administered, with appropriate pre-medication, as two intravenous infusions at a dose of 1g 14 days apart. Synovial tissue was fixed in formalin, paraffin-embedded and cut to serial sections (3μm). Histological grading and lymphoid organization of the synovium was assessed by immunohistochemical analysis. After staining for CD20, the presence or absence of B-cells was determined by a semi-quantitative score (0-4)1. CD21 staining was carried out on samples with large aggregates to determine the presence of FDC in germinal centres (GC) within the synovium. Disease response to treatment (improvement in DAS-28>1.2) at 16 weeks was correlated with the presence or absence of B-cells and GC using Fishers exact test and Chi-squared testing, respectively. Results IHC for CD20 results were available from 39 patients. 29 [74%] patients were females, mean age 58.5 [29-80], 36 [92%] were anti-CCP positive and 32 [82%] were RF positive. 12 [30%] showed a response (DAS-28 >1.2) improvement at 3 months. 24 [62%] patients had little or no B-cell infiltrate within the synovium. In this subgroup, 20 [83%] did not exhibit a significant clinical response. (p=0.031). In B-cell rich non-responders, the presence of GC was noted in 5 out of 6 individuals [83%]; only 1 patient who was GC positive responded to Rituximab. (p=0.01, n=37) Conclusions This open-labeled pilot study strongly suggests that response to Rituximab therapy is determined by the presence or absence of B-cells within the synovium. In patients with B-cell rich synovium, the presence of GC appears to be an important marker of resistance to Rituximab therapy. This pilot study also highlights the potential to utilize synovial pathotype as a biomarker to predict disease outcomes and response. References Kraan, M.C., Haringman, J.J., Post W.J., Versendaal, J., Breedveld, F.C., Tak. P.P. Immunohistological analysis of synovial tissue for differential diagnosis in early arthritis. Rheumatology 1999; 38:1074–1080. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5609

AB0132 Presence of Synovial Lymphocyte Aggregates Correlates with A More Severe Clinical Phenotype in Patients with Early Inflammatory Arthritis

Background Although many observations have suggested that ectopic lymphoid structures within the inflamed synovium are immunologically functional and can support chronic inflammation, their clinical significance is still controversial. Moreover, most of data comes from patients with long standing disease activity, while data in early arthritis is still scarce. In particular, it is unclear whether the presence of lymphocytic aggregates within the synovium correlates with clinical phenotype and degree of inflammation in early inflammatory arthritis patients. Objectives The aim of this study is to evaluate the correlation between synovial lymphocytic aggregates with clinical phenotype in an early inflammatory arthritis cohort. Methods 155 disease-modifying antirheumatic drug-naïve patients with early inflammatory arthritis (<12 months duration, at least 1 swollen joints) has been recruited at Barts and The London Hospital. Baseline disease characteristics assessment included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, rheumatoid factor (RF), anti-cyclic-citrullinated peptide (CCP) and 28 joints-disease activity score (DAS28). Ultrasound-guided synovial biopsy has been obtained for all patients. Sections of paraffin embedded synovial tissue were stained with standard Haematoxylin and Eosin (H&E) and graded as either a diffuse or aggregate synovitis. The degree of lymphoid organisation was further assessed by immnohistochemical staining of sequentially cut sections. The number of lymphocytic aggregates was counted in each section and graded according to a validated, previously published grading system [Manzo, A. et al; European Journal of Immunology2005]. Results The presence of lymphocytic aggregates has been found in almost 30% of patients; Lymphocytic aggregates are associated with increased inflammatory markers and DAS28, as well as RF and CCP seropositivity (p<0.05); The number of B cells and plasma cells in the synovium of early rheumatoid arthritis patients is closely associated (p<0.05), suggesting in situ differentiation. Conclusions The presence of lymphocytic aggregates within the synovium in early arthritis correlates with a more severe clinical phenotype, including inflammatory markers, disease activity and antibody status. Further studies are needed in order to establish the clinical relevance of this association, and in particular its potential prognostic value. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5836

AB0247 Rheumatoid arthritis patient characteristics at different therapeutic timepoints

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease whose pathogenesis and response to therapy may differ at different therapeutic time points. While an immune-mediated inflammation may drive early disease, at late stages, a stromal reaction may prevail. Consequently tailored therapy within any phase of the disease requires better appreciation of both clinical, imaging and histopathological phenotypes. Objectives This study aims to investigate if there are any significant differences in these features at three distinct RA therapeutic timepoints. Methods Data was collected from 54 RA patients from 3 time points i)early RA (EAC), n=20, onset <1 year & prior to starting disease modifying anti rheumatic drug (DMARD) ii) DMARD inadequate responders (DMARDir), n=20, failed ≥2 DMARDS & fulfilling national criteria to start anti TNF and iii)anti TNF inadequate responders (TNFir), n=14, failed ≥1 anti TNF & switching to different biologic agent Prior to changing therapy, all patients had a core data set assessment including clinical, biochemical and imaging including ultrasound (US) of metacarpophlangeal joints and writsts, scored using Eular score (0-3). Patients also underwent an US guided synovial biopsy of a symptomatic joint. Sections of paraffin embedded RA synovial tissue were stained with standard Haematoxylin and Eosin and graded as either a diffuse or aggregate synovitis. Sequentially cut paraffin sections also underwent immunohistochemical staining for B-cells(CD20), T cells (CD3) and macrophages (CD68) and were semi-quantitatively scored (0-4) for each marker. Results Study population was 75% female with a mean age of 53. Mean disease duration was 0.5 years (EAC), 6.9 years (DMARDir) and 15.2 years (TNFir). DAS28 were similar between groups (p = 0.38). Rheumatoid factor and anti-CCP positivity were more prevalent in the DMARDir and TNFir cohorts (p<0.001). US imaging showed no significant difference in the amount of grey scale synovitis (p = 0.78) between groups but significant differences were seen in the amount of Doppler signal between groups (p=0.036). Histological grading was significantly different between groups (p<0.04), with 64% of TNFir group having a diffuse synovitis. Lower levels of T cells (p<0.04) and B cells (p<0.02) within the synovium were also noted in this group. Interestingly, we found a significant correlation between US synovitis with the presence of sublining macrophages in the EAC and DMARDir groups (p<0.01 and p=0.04) which is lost in the TNFir group. Conclusions The association between US synovitis and sublining macrophages, which have been suggested to be predictive of treatment response do suggest that US findings need to be always considered in the context of therapeutic agent and disease duration. Furher studies is needed to evaluate the utility of US to predict treatment response as well. The predominance of a diffuse histological pattern in the TNFir group suggests that this pattern may be associated with treatment resistant RA. Further studies will be needed to evaluate its value as a predictor of TNFir. Disclosure of Interest None Declared

AB0742 Minimally invasive ultrasound guided synovial biopsy as a clinical diagnostic tool

Background Diagnostic synovial biopsies (Bx) are key investigations which traditionally involves an invasive orthopaedic arthroscopic procedure. However, in our department, all our diagnostic synovial biopsies are performed by rheumatologists using a minimally invasive ultrasound (US) guided technique that has been shown to be safe and well tolerated1. Objectives This audit was undertaken to review our activities, outcome (tissue diagnosis), tissue quality and safety of the procedure. Methods 26 patients underwent an outpatient diagnostic synovial biopsy from May 2011 to October 2012. Data was collected from casenotes and online care record system. Biopsies were performed in sterile aseptic conditions. After local anaesthesia, a 16G core Bx needle is placed within the joint capsule under US visualisation and is guided to the appropriate site for sampling. Tissue samples were placed in formalin for histology (Histo) analysis, but kept fresh for microbiology and crystal analysis. Results Activity: Joints Biopsied - knees (n=8, 31%), wrists (n=6, 23%) flexor tendon sheath (n=2, 8%), MCPJs (n=2, 8%), MTPJs (n=2, 8%), ankles (n=2, 8%), shoulder, elbow, PIPJ and DIPJ(n= 1 each, 4%). The commonest indication was to exclude an infective arthritis (n=18, 70%), followed by requests to aid diagnosis of crystal arthritis (n=4, 15%) and sarcoidosis (n=4, 15%). Timing of Bx: 78% of all Bx were performed within 5 days of request, of which 54% within 3 days and 31% within 1 day. Tissue quality: All samples harvested were of good quality for laboratory processing bar 1 biopsy with insufficient tissue for histopathological but enough for microbiology. Safety: A majority of patients (92%) had an uncomplicated Bx. 2 patients (8%) described arthralgia and swelling at Bx site 48 hours post procedure. No evidence of haemarthrosis or infection was found and pain settled with simple analgesia after 2 days. Outcome: 4 cases of TB arthritis were diagnosed (22%, 4/18). 2 patients had granulomas seen on histo, 2 other patients had positive AFB smear. Of those suspected of sarcoidosis, 1 case was positive for granuloma on the flexor tendon sheath, with negative IGRA suggesting sarcoid tenosynovitis. No crystals were seen in any of the samples harvested for cases suspected of crystal arthritis. Follow up: Patients who have received an US guided synovial biopsy with a negative result were diagnosed with an undifferentiated inflammatory arthritis and received immunosuppressive treatment. To date (mean follow up of 13 months), none of these patients were subsequently diagnosed with an infected arthritis suggesting tissue samples for microbial analysis were adequate for accurate analysis. Conclusions Minimally invasive US guided synovial biopsy is a valuable clinical diagnostic tool that enables safe, quick and adequate tissue sampling for microbiology and histopathological analysis. We would suggest for this technique to be introduced in other rheumatology centres as a clinical diagnostic tool. Larger number of biopsies will need to be looked at to better determine the negative predictive value of this tool in the context of suspected septic arthritis. References Kelly S, et al. Ultrasound guided synovial biopsies: safety, tolerability and tissue quality. Rheumatology 2012; 51(suppl 3): iii52-iii92 Disclosure of Interest None Declared