tbuckley/cabot-search huggingface dataset:
O007 ACPA-induced mobility of primed synovial fibroblasts: the missing link between ACPA-induced bone loss and synovial changes
Authors: M Sun, B Rethi, V Joshua, A Krishnamurthy, A Hensvold, SB Catrina, C Ospelt, V Malmström, J Steen, M Engström, H Wähämaa, AI Catrina
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Anti-citrullinated proteins antibodies (ACPAs) injected in mice induce IL-8 dependent bone loss and arthralgia, but no synovial changes. We hypothesised that additional stimuli, sensitising the synovial compartment to ACPA effects, might be needed for the transition from bone to synovial pathology. <h3>Methods</h3> Fibroblast like synoviocytes (FLSs) were isolated from synovial tissue biopsies obtained from RA patients. Polyclonal ACPA and other non-ACPA IgGs were separated from peripheral blood of RA patients by affinity purification on protein G and cyclic citrullinated peptide (CCP)−2 columns. Monoclonal ACPAs were cloned from synovial fluid B-cells. FLS migration was tested by scratch-assays using IncuCyte (Essen bioscience). SF adhesion was analysed by xCELLigence System Real-Time Cell Analyzer (ACEA bioscience). Peptidylarginine deiminases (PAD) expression and protein citrullination were evaluated by immunohistochemistry and immunofluorescent stainings. <h3>Results</h3> FLS mobility was not affected by polyclonal ACPA stimulation. However, exposing the cells to IL-8 or to a transient serum starvation increased PAD expression and the amount of citrullinated proteins in the cells. In line with these findings, starved FLSs obtained sensitivity to ACPAs and responded with an increased mobility to antibody stimulation. Similar effects were observed in the presence of three out of ten monoclonal ACPAs, suggesting that only APCAs with certain fine specificity could target FLSs. The ACPA-induced migration was abolished by pre-incubating the cells with PAD inhibitor or by combining the ACPAs with citrullinated but not native fibrinogen. IL-8 alone could not influence fibroblast migration but it synergistically increased the response to ACPAs. The role for inflammatory stimuli in sensitising FLSs to ACPA binding was further supported by the labelling of synovial tissues of RA patient, but not of healthy controls, using monoclonal ACPAs. <h3>Conclusions</h3> We demonstrated that FLS response to ACPA stimulation was enabled by stress- or cytokine-induced citrullination in the cells. These results suggest an important role for transient synovial insults in setting the stage for the ACPA-mediated transition towards chronic synovitis. <h3>Disclosure of interest</h3> None declared
Mast cells and sphingosine‐1‐phosphate underlie prelesional remodeling in a mouse model of eczema
Authors: P. A. Wedman, A. Aladhami, A. P. Chumanevich, J. W. Fuseler, C. A. Oskeritzian
Journal: Allergy (2017)

Abstract Background Atopic dermatitis ( AD ) is a chronic skin inflammation that affects children and adults worldwide, but its pathogenesis remains ill‐understood. Methods We show that a single application of OVA to mouse skin initiates remodeling and cellular infiltration of the hypodermis measured by a newly developed computer‐aided method. Results Importantly, we demonstrate that skin mast cell ( MC ) activation and local sphingosine‐1‐phosphate (S1P) are significantly augmented after OVA treatment in mice. Deficiency in sphingosine kinase (SphK)1, the S1P‐producing enzyme, or in MC , remarkably mitigates all signs of OVA ‐mediated remodeling and MC activation. Furthermore, skin S1P levels remain unchanged in MC ‐deficient mice exposed to OVA . LPS ‐free OVA does not recapitulate any of the precursor signs of AD , supporting a triggering contribution of LPS in AD that, per se , suffice to activate local MC and elevate skin S1P. Conclusion We describe MC and S1P as novel pathogenic effectors that initiate remodeling in AD prior to any skin lesions and reveal the significance of LPS in OVA used in most studies, thus mimicking natural antigen (Ag) exposure.
FRI0422 Estrogen attenuates the disease activity of spondyloarthritis in skg mice
Authors: H Jeong, E-K Bae, YH Eun, IY Kim, E-J Park, J Lee, E-M Koh, H-S Cha
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Ankylosing spondylitis is a male-predominant disease, and the male gender is also associated with more severe radiographic damage. Estrogen modulates immune-related processes such as T cell differentiation and cytokine production. <h3>Objectives</h3> This study aimed to evaluate the role of estrogen in the disease activity of spondyloarthritis (SpA). The effect of estrogen on the inflammatory cytokines was evaluated. <h3>Methods</h3> The effects of estrogen on the development of arthritis were evaluated by performing an ovariectomy and E2 pellet implantation in the zymosan-treated SKG mouse. Clinical arthritis scores were measured and PET-CT was performed to quantify joint inflammation. Total RNA was extracted from the hindpaws and forepaws and the expression of TNFα, IL-6, IFNγ, IL-4, IL-17A, IL-23, Dkk1, and SOST was measured by QuantiGene 2.0 plex assay. <h3>Results</h3> Zymosan exposure triggered SpA-like diseases in SKG mice, including peripheral arthritis, spondylitis, dactylitis, enteritis, and psoriatic skin lesions. E2-treated mice showed remarkable suppression of arthritis clinically and little infiltration of inflammatory cells in the Achilles tendon and intervertebral disc. <sup>18</sup>F-FDG uptake was significantly lower in the E2-treated mice. The expression of TNFα, IFNγ, IL-17A, Dkk1, and SOST was significantly reduced in E2-treated mice compared with sham and ovariectomized mice. <h3>Conclusions</h3> Estrogen suppressed arthritis development in SpA model of SKG mouse. Results of the study suggest that estrogen may have an anti-inflammatory effect on the disease activity of SpA. <h3>Disclosure of Interest</h3> None declared
The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial
Authors: Rohit Loomba, Eric Lawitz, Parvez S. Mantry, Saumya Jayakumar, Stephen H. Caldwell, Hays Arnold, Anna Mae Diehl, C. Stephen Djedjos, Ling Han, Robert P. Myers, G. Mani Subramanian, John G. McHutchison, Zachary D. Goodman, Nezam H. Afdhal, Michael R. Charlton
Journal: Hepatology (2017)

Inhibition of apoptosis signal-regulating kinase 1, a serine/threonine kinase, leads to improvement in inflammation and fibrosis in animal models of nonalcoholic steatohepatitis. We evaluated the safety and efficacy of selonsertib, a selective inhibitor of apoptosis signal-regulating kinase 1, alone or in combination with simtuzumab, in patients with nonalcoholic steatohepatitis and stage 2 or 3 liver fibrosis. In this multicenter phase 2 trial, 72 patients were randomized to receive 24 weeks of open-label treatment with either 6 or 18 mg of selonsertib orally once daily with or without once-weekly injections of 125 mg of simtuzumab or simtuzumab alone. The effect of treatment was assessed by paired pretreatment and posttreatment liver biopsies, magnetic resonance elastography, magnetic resonance imaging-estimated proton density fat fraction, quantitative collagen content, and noninvasive markers of liver injury. Due to the lack of effect of simtuzumab on histology or selonsertib pharmacokinetics, selonsertib groups with and without simtuzumab were pooled. After 24 weeks of treatment, the proportion of patients with a one or more stage reduction in fibrosis in the 18-mg selonsertib group was 13 of 30 (43%; 95% confidence interval, 26-63); in the 6-mg selonsertib group, 8 of 27 (30%; 95% confidence interval, 14-50); and in the simtuzumab-alone group, 2 of 10 (20%; 95% confidence interval, 3-56). Improvement in fibrosis was associated with reductions in liver stiffness on magnetic resonance elastography, collagen content and lobular inflammation on liver biopsy, as well as improvements in serum biomarkers of apoptosis and necrosis. There were no significant differences in adverse events between the treatment groups. Conclusion: These findings suggest that selonsertib may reduce liver fibrosis in patients with nonalcoholic steatohepatitis and stage 2-3 fibrosis. (Hepatology 2018;67:549-559).
AB0979 Eosinophilic fascitis: clinical experience in a series of 21 patients
Authors: JC Quevedo, R Lopez, M Garcia-Bustuinduy, C Rodriguez-Lozano, B Rodriguez-Lozano, S Bustabad, E Trujillo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The Eosinophilic fascitis (EF) is a uncommon sclerodermiforme síndrome with unknown etiology and poorly understood pathogenesis and natural evolution. The published series are short, with a total of 280 cases described in the literature from 1974. There is neither clinical tests nor consensus on the EF treatment. <h3>Objectives</h3> To describe a series of 21 patients with EF. <h3>Methods</h3> Multicentric, retrospective Case Series Study. We reviewed 21 patients diagnosed of EF (cutaneous induration+consistent biopsy) between January 1998 to January 2015. A total of 13 males and 8 females. <h3>Results</h3> The mean age at diagnosis was 41 years 8range between 28 and 66). Trigger factor was suspected in 8 patients (intense exercise in 7). The zones of cutaneous affectation were fundamentally the upper and low extremities. The hyperesonophilia was present in 100% of the patients. The average of the % more high of hyperesosinophilia was 21.2% (range 4–45.4%). 11 patients presented artralgias and 5 patients presented arthritis (4 polyarticular/1 oligoarticular). The MRI was used for diagnosis and/or follow-up in 8 patients, especially in the diagnosed ones in the last 5 years. The average initial dose of prednisone was 40 mg/día, the average maximum dose of prednisone was 40 mg/dia and the mean steroid treatment duration was 22 months (range 9–47 months). Other immunomodulatory agents were: methotrexate 11, hydroxychloroquine 2, azatioprina 2 and D penicillamine 1. 5 years after follow-up, the evolution was the complete resolution in 13 patients and the partial improvement in 6. <h3>Conclusions</h3> In our series, the EF prevails in males, in the decade of the 40 and in the majority one did not find trigger factor. There was presence of arthritis in a significant percentage of patients. In the last years the use of the RMN has been added to the diagnosis and to the follow-up. Though there are no clinical tests that support it the use of the metotrexato has been generalized as adjuvant treatment to the steroids. <h3>Disclosure of Interest</h3> None declared
Efficacy and Safety of Hydroxychloroquine Sulphate In Chronic Lymphocytic Leukemia: Clinical Trial Experience In Untreated Patients
Authors: Shih-Shih Chen, Matthew Kaufman, Angelica Caramanica, Rajendra N Damle, Peter Garofalo, Patricia Ly, Dale Janson, Steven L. Allen, Jonathan Kolitz, Linda Quill, Kanti R. Rai, Nicholas Chiorazzi
Journal: Blood (2010)
SAT0234 Prospective single centre study of effectiveness of upfront rituximab and mycophenolate with minimum steroid in sle
Authors: BG Dharmanand
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Treatment options for SLE have significant morbidity and mortality. Side effects from corticosteroid usage limit patient adherence and treatment efficacy. B cell depletion appears to target a critical pathophysiological pathway in SLE. Trails with rituximab have shown mixed results. Rituxilup study demonstrated efficacy and steroid sparing action of rituximab and mycophenolate (1) <h3>Objectives</h3> We aim to analyse our experience of using rituximab and mycophenolate upfront on presentation with minimum oral steroids. <h3>Methods</h3> 12 patients with SLE, seen between Jan 2015 to march 2016, were included in the study. All patients completed 6 months of follow-up. Patients were treated with 2 doses of rituximab (1 g) and methyl prednisolone (500 mg) on days 1 and 15, and maintenance treatment of mycophenolate mofetil (2000mg) and low dose prednisolone (&lt;7.5 mg) which was tapered off. <h3>Results</h3> 10 were females and 2 males. Mean age of the patients is 24.5. 9 had lupus nephritis, 1 mesenteric vasculitis, 1 CNS vasculitis and 1 severe cutaneous vasculitis with pancytopenia. Average SLEDAI improved from 14 to 4. 6/9 LN attained complete renal remission and 2 partial remission. one patient died due to infection and renal disease 15 days after infusion. 2 vasculitis and one NPSLE patient improved completely. Two patients had infection requiring hospitalization with in 8 weeks of infusion and one patient had severe bradycardia during the infusion and received only 1000mg rituximab. Steroid was stopped by 6 months in 6 patients and in the dose was below 5 mg in rest. <h3>Conclusions</h3> Early Rituximab and mycophenolate is an effective option for treating severe lupus and has steroid sparing property. <h3>References</h3> Condon MB, Ashby D, Pepper RJ, et al. Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids. Ann Rheum Dis (2013) 72:1280–1286. <h3>Disclosure of Interest</h3> None declared
SIMPLIFY-1: A Phase III Randomized Trial of Momelotinib Versus Ruxolitinib in Janus Kinase Inhibitor–Naïve Patients With Myelofibrosis
Authors: Ruben A. Mesa, Jean-Jacques Kiladjian, John V. Catalano, Timothy Devos, Miklos Egyed, Andrzei Hellmann, Donal McLornan, Kazuya Shimoda, Elliott F. Winton, Wei Deng, Ronald L. Dubowy, Julia D. Maltzman, Francisco Cervantes, Jason Gotlib
Journal: Journal of Clinical Oncology (2017)

Purpose We evaluated the efficacy and safety of momelotinib, a potent and selective Janus kinase 1 and 2 inhibitor (JAKi), compared with ruxolitinib, in JAKi-naïve patients with myelofibrosis. Patients and Methods Patients (N = 432) with high risk or intermediate-2 risk or symptomatic intermediate-1 risk myelofibrosis were randomly assigned to receive 24 weeks of treatment with momelotinib 200 mg once daily or ruxolitinib 20 mg twice a day (or per label), after which all patients could receive open-label momelotinib. The primary end point was a ≥ 35% reduction in spleen volume at 24 weeks of therapy. Secondary end points were rates of symptom response and effects on RBC transfusion requirements. Results A ≥ 35% reduction in spleen volume at week 24 was achieved by a similar proportion of patients in both treatment arms: 26.5% of the momelotinib group and 29% of the ruxolitinib group (noninferior; P = .011). A ≥ 50% reduction in the total symptom score was observed in 28.4% and 42.2% of patients who received momelotinib and ruxolitinib, respectively, indicating that noninferiority was not met ( P = .98). Transfusion rate, transfusion independence, and transfusion dependence were improved with momelotinib (all with nominal P ≤ .019). The most common grade ≥ 3 hematologic abnormalities in either group were thrombocytopenia and anemia. Grade ≥ 3 infections occurred in 7% of patients who received momelotinib and 3% of patients who received ruxolitinib. Treatment-emergent peripheral neuropathy occurred in 10% of patients who received momelotinib (all grade ≤ 2) and 5% of patients who received ruxolitinib (all grade ≤ 3). Conclusion In JAKi-naïve patients with myelofibrosis, 24 weeks of momelotinib treatment was noninferior to ruxolitinib for spleen response but not for symptom response. Momelotinib treatment was associated with a reduced transfusion requirement.
THU0545 Comparison of the clinical and laboratory features at onset between multicentric castleman's disease and adult-onset still's disease
Authors: A García González, WA Sifuentes Giraldo, JL Morell Hita, JL de la Peña Patier
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Multicentric Castleman9s disease (MCD) is a disorder characterized by polyclonal proliferation of B lymphocytes that is frequently associated with autoimmune manifestations and connective tissue diseases. MCD presents high levels of IL-6 and systemic symptoms such as fever, arthralgia, hepatosplenomegaly and serositis, so it is recommended to include MCD in the differential diagnosis of adult-onset Still9s disease (AOSD). However, there are no studies comparing both groups of patients. <h3>Objectives</h3> To compare the clinical and laboratory features at onset between patients with MCD and AOSD seen in a Madrid tertiary care hospital. <h3>Methods</h3> We performed a retrospective observational study in patients with diagnosis MCD and AOSD attended our center between January 1989 and December 2015. The variables included demographics, clinical manifestations, laboratory tests and Yamaguchi9s criteria. <h3>Results</h3> A total of 34 patients were included, 17 with MCD and 17 with AOSD. The comparison of the characteristics of both groups is presented in the table. There were no differences in age, uration of disease (MCD 158,6 days and AOSD 250,5 days, p=0,3919), diagnostic delay (MCD 18,4 and AOSD 52,2, p=0,2711), arthritis, myalagias, pleuritis or macrophagic activation syndrome, but persistent fever, rash, arthralgia, pharyngitis and pericarditis were significantly more frequent in ESA, whereas male gender, human immunodeficiency virus (HIV) and/or human herpes virus 8 (HHV8) infection, hepatosplenomegaly and lymphadenopathy were significantly higher in MCD. In the laboratory test results, leukocytosis and hypertransaminasemia were significantly higher in AOSD. 52.9% of patients with MCD met 5 or more Yamaguchi9s criteria for AOSD. <h3>Conclusions</h3> Patients with MCD may present common systemic manifestations and laboratory abnormalities at onset with AOSD and up to 50% of them may fulfill Yamaguchi9s criteria for this disease, so MCD should be taken into account in its differential diagnosis. <h3>Disclosure of Interest</h3> None declared
AB0409 Corticosteroid-sparing in patients with rheumatoid arthritis on tocilizumab: first experience of bab -el- oued hospital
Authors: MA Ifticene, H Hafirassou, R Benaziez, F Mechid, F Hanni, C Dahou Makhloufi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Tocilizumab (TCZ) is a monoclonal antibody directed against the IL-6 receptors. This treatment (TRT) allows for the cortisone weaning in preventing of its complications. <h3>Objectives</h3> The goal of this study is to evaluate the corticosteroid sparing in patients with RA treated with TCZ. <h3>Methods</h3> Prospective, descriptive study of patients hospitalized between 2012 and 2016, the diagnosis was made according to the ACR 1987 ACR/EULAR 2010 criteria. Included, are the patients treated with TCZ for at least 3 months associated with corticosteroids. We have studied the following: the epidemiology, the associated DMARDs, the average DAS28VS, the average dosage of prednisone-equivalent and the percentage of patients with decreased or interrupted corticosteroids at M0, M3, M6 and M12. <h3>Results</h3> 26 patients (sex ratio: 0.7) treated with TCZ and corticosteroids, average age is 43.4 years (range 30–62). Average duration of the development of RA: 9.1±6.4 years. DMARDs was associated in 15 patient. At baseline, 46.2% of patients were on 10 mg/day of cortisone, the average dose of prednisone-equivalent was at 7.7±3.6mg at M0, 5.3±3.2 mg at M3, 4.6±2.3 mg at M6, 2.6±2.6 mg at M12 with a statistically significant difference (p=0.000003). The average DASVS28 activity index was 5.6±0.9 at M0, 3.5±1.3 at M3, 3.04±1.2 at M6 and 2.6 ± M6 at M12 with a statistically significant difference (p&lt;0.000001). Corticosteroid treatment was stopped in 12 patients after 1 year of treatment. <h3>Conclusions</h3> Through this study we note that the TRT using TCZ has enabled a significant reduction in the dose of corticosteroids. Stopping prednisone was possible in 50% of patients after 1 year of biotherapy. <h3>Disclosure of Interest</h3> None declared
AB0405 Safety of rituximab therapy in autoimmune diseases:systematic review and meta-analysis
Authors: K Kobayashi, KM Minegishi, N Horita, S Ohno, HN Nakajima
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Treatment with rituximab (RTX), a chimeric CD20 monoclonal antibody, has demonstrated efficacy for patients with several autoimmune diseases. There is a growing concern, however, safety evidence of RTX is still lacking. <h3>Objectives</h3> We conducted to evaluate the safety of rituximab (RTX) for autoimmune diseases. <h3>Methods</h3> A literature review was performed based on the randomized clinical trials (RCTs) that assessed adverse events by comparing RTX and placebo or no treatment for autoimmune diseases. The same add-on treatment for both arms were allowed. Study selection and data extraction were independently conducted in duplicate. Meta-analyses were performed for each outcome separately using fixed model and generic inverse variance method. <h3>Results</h3> In the primary analysis, 16 eligible RCTs, with a total of 4147 patients for five autoimmune diseases (n=8: rheumatoid arthritis, n=3: Sjogren syndrome, n=1: systemic lupus erythematosus, multiple sclerosis, ulcerative colitis, Graves orbitopathy, immune thrombocytopenia) were analyzed. The incidence of infusion related reactions and the human antichimeric antibody (HACA) were higher in RTX group than placebo/no treatment group (OR 1.49, 95% CI 1.25–1.77 and OR 2.25, 95% CI 1.35–3.76, respectively). However, there were no significant differences the odds of total adverse events, serious adverse events, withdrawal for adverse events, infections, serious infections, malignancy, and all-cause death between two groups. <h3>Conclusions</h3> Our meta-analysis revealed that RTX was not associated with an increased risk of adverse events except for infusion related reactions and the incidence of HACA compared with placebo. <h3>Acknowledgements</h3> <h3>Disclosure of Interest</h3> None declared