tbuckley/cabot-search huggingface dataset:
THU0068 The risk of individual autoantibodies, autoantibody combinations and autoantibody levels for arthritis development in clinically suspect arthralgia
Authors: RM Ten Brinck, HW van Steenbergen, MA van Delft, MK Verheul, RE Toes, LA Trouw, AH van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Autoantibody testing is helpful to predict progression to arthritis in subjects at risk. Previous longitudinal studies mainly focussed on autoantibody-positive arthralgia patients. Consequently predictive values of autoantibodies were evaluated relative to each other. This study assessed risks of having anticitrullinated protein antibodies (ACPA), rheumatoid factor (RF) and/or anti-carbamylated protein antibodies (anti-CarP) for arthritis development in arthralgia patients considered at risk for RA by rheumatologists based on clinical characteristics (Clinically Suspect Arthralgia, CSA). <h3>Objectives</h3> To assess risks of having anticitrullinated protein antibodies (ACPA), rheumatoid factor (RF) and/or anti-carbamylated protein antibodies (anti-CarP) for arthritis development in arthralgia patients considered at risk for RA by rheumatologists based on clinical characteristics (CSA). <h3>Methods</h3> Baseline ACPA, RF and anti-CarP antibodies of 241 patients, consecutively included in the CSA-cohort, were studied in relation to development of clinical arthritis during a median follow-up of 103 (IQR 81–114) weeks. <h3>Results</h3> ACPA, RF and anti-CarP antibodies were all univariably associated with arthritis development, hazard ratios (95% CI) were 8.5 (4.7–15.5), 5.1 (2.8–9.3) and 3.9 (1.9–7.7). Only ACPA, and not RF or anti-CarP, was independently associated (HR 5.1, 2.0–13.2). Relative to autoantibody-negative CSA-patients, ACPA-negative/RF-positive patients had HRs of 2.6 (1.04–6.6), ACPA-positive/RF-negative patients 8.0 (2.4–27.4), and ACPA-positive/RF-positive patients 10.5 (5.4–20.6, Figure). PPVs for development of clinical arthritis within two years were: 38% for ACPA-negative/RF-positive, 50% for ACPA-positive/RF-negative, and 67% for ACPA-positive/RF-positive patients. Higher ACPA-levels were not significantly associated with increased progression to clinical arthritis, in contrast to higher RF-levels. Autoantibody levels were stable during follow-up. <h3>Conclusions</h3> ACPA conferred the highest risk for arthritis development and had an additive value to RF. However, &gt;30% of ACPA-positive/RF-positive CSA-patients did not develop arthritis during two-year follow-up. Thus CSA and information on autoantibodies is insufficient to accurately identify imminent autoantibody-positive RA. <h3>Disclosure of Interest</h3> None declared
AB0002 Genetic study of three-prime repair exonuclease (TREX1) in the susceptibility to systemic lupus erythematosus (SLE) among egyptian patients
Authors: D El Dessouki, MS Abdel-Hamid, L Effat, M Niazy, N Kholoussi, G Abdel Moneim, GM Abdel-Salam
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Interferon-alpha (IFNα) pathway has a crucial role in the pathogenesis of SLE. Many genes have been encoding with this pathway and their impaired expression have been reported in patients with SLE. <i>TREX1</i> is a DNA exonuclease involved in the metabolism and clearance of single stranded DNA from apoptotic cells, which is impaired in SLE<sup>1</sup>. <i>TREX1</i> mutations have been reported in SLE<sup>2</sup>. <h3>Objectives</h3> Our study was aiming to assess the role of <i>TREX1</i> in the genetic susceptibility to systemic lupus erythematosus (SLE) among Egyptian patients. <h3>Methods</h3> Fifty SLE Egyptian patients and 50 age &amp; sex matched healthy controls were included in this study. Based on the clinical history and immunological investigations, the 50 SLE patients were divided into two groups according to the presence of positive family history of autoimmune disease: Group I: 28 patients with positive family history &amp; Group II: 22 patients with no family history. Further, the single exon of <i>TREX1</i> and its flanking sequences were amplified by PCR and sequenced in both directions. <h3>Results</h3> Our work showed a recurrent <i>TREX1</i> polymorphism rs11797 (c.531C&gt;T) among Egyptian patients (56%) in comparison to control group (36%) (p value of 0.070) especially in cases with NPSLE, seizures and chilblains; with minor allele frequency of 0.28 in cases and 0.18 in controls (p value=0.342). <i>TREX1</i> polymorphism was present in 57.1% patients (16/28) of SLE patients in group I versus 54.5% patients (12/22) of SLE cases in, group II. The polymorphism was positively associated with neuropsychiatric manifestations (OR=7.000, 95% CI=0.791–61.975) and chilblains (OR=10.532, 95% CI=0.550–201.679). Furthermore, there was a statistically significant difference in cases with oral ulcers (p value=0.004), photosensitivity (p value=0.047) and seizures (p value=0.029). <h3>Conclusions</h3> We confirm that rs11797 (c.531C&gt;T) could be associated with the susceptibility to neurological manifestations among the studied SLE patients. <h3>References</h3> Hur JW, Sung YK, Shin HD, Park BL, Cheong HS, and Bae SC (2008): TREX1 polymorphisms associated with autoantibodies in patients with systemic lupus erythematosus. Rheumatol Int; 28:783–789. Lee-Kirsch MA, Gong M, Chowdhury D, Senenko L, Engel K, Lee YA, et al. (2007): Mutations in the gene encoding the 39-59 DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat Genet; 39(9):1065–7. <h3>Disclosure of Interest</h3> None declared
Dose Comparison Study of Allogeneic Mesenchymal Stem Cells in Patients With Ischemic Cardiomyopathy (The TRIDENT Study)
Authors: Victoria Florea, Angela C. Rieger, Darcy L. DiFede, Jill El-Khorazaty, Makoto Natsumeda, Monisha N. Banerjee, Bryon A. Tompkins, Aisha Khan, Ivonne H. Schulman, Ana Marie Landin, Muzammil Mushtaq, Samuel Golpanian, Maureen H. Lowery, John J. Byrnes, Robert C. Hendel, Mauricio G. Cohen, Krystalenia Valasaki, Marietsy V. Pujol, Eduard Ghersin, Roberto Miki, Cindy Delgado, Fouad Abuzeid, Mayra Vidro-Casiano, Russell G. Saltzman, Daniel DaFonseca, Lina V. Caceres, Kevin N. Ramdas, Adam Mendizabal, Alan W. Heldman, Raul D. Mitrani, Joshua M. Hare
Journal: Circulation Research (2017)

Rationale: Cell dose and concentration play crucial roles in phenotypic responses to cell-based therapy for heart failure. Objective: To compare the safety and efficacy of 2 doses of allogeneic bone marrow–derived human mesenchymal stem cells identically delivered in patients with ischemic cardiomyopathy. Methods and Results: Thirty patients with ischemic cardiomyopathy received in a blinded manner either 20 million (n=15) or 100 million (n=15) allogeneic human mesenchymal stem cells via transendocardial injection (0.5 cc per injection × 10 injections per patient). Patients were followed for 12 months for safety and efficacy end points. There were no treatment-emergent serious adverse events at 30 days or treatment-related serious adverse events at 12 months. The Major Adverse Cardiac Event rate was 20.0% (95% confidence interval [CI], 6.9% to 50.0%) in 20 million and 13.3% (95% CI, 3.5% to 43.6%) in 100 million ( P =0.58). Worsening heart failure rehospitalization was 20.0% (95% CI, 6.9% to 50.0%) in 20 million and 7.1% (95% CI, 1.0% to 40.9%) in 100 million ( P =0.27). Whereas scar size reduced to a similar degree in both groups: 20 million by −6.4 g (interquartile range, −13.5 to −3.4 g; P =0.001) and 100 million by −6.1 g (interquartile range, −8.1 to −4.6 g; P =0.0002), the ejection fraction improved only with 100 million by 3.7 U (interquartile range, 1.1 to 6.1; P =0.04). New York Heart Association class improved at 12 months in 35.7% (95% CI, 12.7% to 64.9%) in 20 million and 42.9% (95% CI, 17.7% to 71.1%) in 100 million. Importantly, proBNP (pro-brain natriuretic peptide) increased at 12 months in 20 million by 0.32 log pg/mL (95% CI, 0.02 to 0.62; P =0.039), but not in 100 million (−0.07 log pg/mL; 95% CI, −0.36 to 0.23; P =0.65; between group P =0.07). Conclusions: Although both cell doses reduced scar size, only the 100 million dose increased ejection fraction. This study highlights the crucial role of cell dose in the responses to cell therapy. Determining optimal dose and delivery is essential to advance the field, decipher mechanism(s) of action and enhance planning of pivotal Phase III trials. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02013674.
THU0342 Utilizing “real life” data in order to evaluate the association between giant cell arteritis and autoimmune thyroid disease
Authors: Y Yavne, S Tiosano, A Watad, D Comaneshter, Y Shoenfeld, AD Cohen, H Amital
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In 1977, How et al.<sup>1</sup> described the case of a simultaneous presentation of giant cell arteritis (GCA) and hypothyroidism. In the following decades, numerous studies have attempted to determine whether a significant interaction exists between GCA and autoimmune thyroid dysfunction, with conflicting results<sup>2–5</sup>. <h3>Objectives</h3> To evaluate whether a genuine association exists between GCA and autoimmune thyroid disease. <h3>Methods</h3> Utilizing the medical database of Clalit Health Services, we compared the proportion of autoimmune thyroid disease between patients with GCA and age- and gender-matched controls in a cross-sectional study. Univariate analysis was performed using Chi-square and student <i>t-test</i> and a multivariate analysis was performed using a logistic regression model. <h3>Results</h3> 5,663 GCA patients and 23,308 age- and gender-matched controls were included in the study. The proportion of hypothyroidism amongst GCA patients was increased in comparison with controls (18.2% vs. 6.91%, respectively, <i>p</i>-<i>value</i> &lt;0.001), as was hyperthyroidism (2.56% and 1.19% respectively, <i>p</i>-<i>value</i> &lt;0.001). After controlling for confounders, GCA demonstrated a robust independent association with hypothyroidism on multivariate logistic regression (OR 1.297, 95% CI 1.187–1.418, Table 1). In contrast, when a similar model was performed in order to assess the nature of the association between GCA and hyperthyroidism, it was found to be non-significant, with an OR of 1.097. <h3>Conclusions</h3> GCA patients have a higher proportion of hypothyroidism in comparison with matched controls. A significant association between GCA and hyperthyroidism was not found. Physicians treating GCA patients should consider screening for thyroid dysfunction on a regular basis. <h3>References</h3> How J, Bewsher PD, Walker W. Giant-cell arteritis and hypothyroidism. Br Med J. 1977;2(6079):99. Wiseman P, Stewart K, Rai GS. Hypothyroidism in polymyalgia rheumatica and giant cell arteritis. BMJ. 1989;298(6674):647. Bowness P, Shotliff K, Middlemiss A, Myles AB. Prevalence of hypothyroidism in patients with polymyalgia rheumatica and giant cell arteritis. Rheumatology. 1991;30(5):349–351. Duhaut P, Bornet H, Pinède L, et al. Giant cell arteritis and thyroid dysfunction: multicentre case-control study. BMJ. 1999;318(7181):434–435. Myklebust G, Gran JT. A prospective study of 287 patients with polymyalgia rheumatica and temporal arteritis: clinical and laboratory manifestations at onset of disease and at the time of diagnosis. Rheumatology. 1996;35(11):1161–1168. <h3>Disclosure of Interest</h3> None declared
Prevalence of hepatitis D virus infection in sub-Saharan Africa: a systematic review and meta-analysis
Authors: Alexander J Stockdale, Mas Chaponda, Apostolos Beloukas, Richard Odame Phillips, Philippa C Matthews, Athanasios Papadimitropoulos, Simon King, Laura Bonnett, Anna Maria Geretti
Journal: The Lancet Global Health (2017)

BackgroundHepatitis D virus (also known as hepatitis delta virus) can establish a persistent infection in people with chronic hepatitis B, leading to accelerated progression of liver disease. In sub-Saharan Africa, where HBsAg prevalence is higher than 8%, hepatitis D virus might represent an important additive cause of chronic liver disease. We aimed to establish the prevalence of hepatitis D virus among HBsAg-positive populations in sub-Saharan Africa.MethodsWe systematically reviewed studies of hepatitis D virus prevalence among HBsAg-positive populations in sub-Saharan Africa. We searched PubMed, Embase, and Scopus for papers published between Jan 1, 1995, and Aug 30, 2016, in which patient selection criteria and geographical setting were described. Search strings included sub-Saharan Africa, the countries therein, and permutations of hepatitis D virus. Cohort data were also added from HIV-positive populations in Malawi and Ghana. Populations undergoing assessment in liver disease clinics and those sampled from other populations (defined as general populations) were analysed. We did a meta-analysis with a DerSimonian-Laird random-effects model to calculate a pooled estimate of hepatitis D virus seroprevalence.FindingsOf 374 studies identified by our search, 30 were included in our study, only eight of which included detection of hepatitis D virus RNA among anti-hepatitis D virus seropositive participants. In west Africa, the pooled seroprevalence of hepatitis D virus was 7·33% (95% CI 3·55–12·20) in general populations and 9·57% (2·31–20·43) in liver-disease populations. In central Africa, seroprevalence was 25·64% (12·09–42·00) in general populations and 37·77% (12·13–67·54) in liver-disease populations. In east and southern Africa, seroprevalence was 0·05% (0·00–1·78) in general populations. The odds ratio for anti-hepatitis D virus detection among HBsAg-positive patients with liver fibrosis or hepatocellular carcinoma was 5·24 (95% CI 2·74–10·01; p<0·0001) relative to asymptomatic controls.InterpretationFindings suggest localised clusters of hepatitis D virus endemicity across sub-Saharan Africa. Epidemiological data are needed from southern and east Africa, and from patients with established liver disease. Further studies should aim to define the reliability of hepatitis D virus testing methods, identify risk factors for transmission, and characterise the natural history of the infection in the region.FundingWellcome Trust, Royal Society.
AB0245 District differences between the sexes of predictive value of matrix metalloproteinase-3 at baseline regarding changes in modified total sharp score at 1 year in patients with rheumatoid arthritis
Authors: K Inui, T Okano, K Orita, Y Sugioka, K Mamoto, T Koike, M Tada, H Nakamura
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Matrix metalloproteinase (MMP)-3, also known as stromelysis-1, is expressed in inflamed synovium of patients with rheumatoid arthritis (RA). It degrades components of articular cartilage, such as proteoglycans. In Japan MMP-3 has been used as a clinical biomarker of joint destruction and its predictive value for radiographic progression has been reported. <h3>Objectives</h3> W aimed to confirm a relation between baseline MMP-3 and radiographic progression at 1 year and to examine the association of the MMP-3 level with ultrasonography (US) findings. <h3>Methods</h3> A total of 259 (213 women) consecutive patients with RA were enrolled. We collected baseline data, that included the patient9s age, sex, disease duration, use of glucocorticoid or disease modifying antirheumatic drugs, Disease Activity Score-28, and modified total Sharp score (mTSS); MMP-3 and, C reactive protein levels;, rheumatoid factor or anti-citrullinated peptide antibody status,; and the power doppler score (PD) of US assessment of digits and wrists. Baseline MMP-3 level was analyzed in association with the baseline PD value and changes (Δ) in mTSS, erosion score (ΔERN), joint space narrowing (ΔJSN) at 1 year from baseline by Pearson9s correlation method. Correlations between ΔMMP-3 and ΔmTSS, or ΔPD were also analyzed. Multiple regression analysis was performed, with ΔmTSS as the outcome for baseline variables. Statistical analysis was performed separately by sex because the upper normal limits of MMP-3 differ between the sexes (men ≤121ng/ml, women ≤59.7 ng/ml). <h3>Results</h3> There was a weak correlation between the baseline MMP-3 level and baseline PD score in men. There was also moderate correlations between baseline MMP-3 level and structural damage at 1 year only in men. There was no predictive value for baseline MMP-3 level in women in terms of structural damage at 1 year. Multiple regression analysis revealed that the baseline MMP-3 level correlated independently with the ΔmTSS only in men (p=0.0031), whereas in the women the baseline PD score was correlated independently with the ΔmTSS (p=0.0003). <h3>Conclusions</h3> The baseline MMP-3 level was a good predictor of deterioration of the mTSS at 1 year in male patients with RA, but not in female patients. On the other hand, the baseline PD score was a useful predictor of joint destruction in female patients with RA. <h3>Disclosure of Interest</h3> None declared
SP0112 Which drugs in pregnant patients?
Authors: M Ostensen
Journal: Annals of the Rheumatic Diseases (2017)

Management of rheumatic disease during pregnancy starts with prepregnancy counselling.Assessment of maternal and fetal risks is necessary for adjusting therapy before and during pregnancy. The aim of therapy is to keep the disease in remission or at least at low activity throughout pregnancy. Immunosuppressive drugs requiring withdrawal before conception are methotrexate, cyclophosphamide,and mycophenolate which are known teratogenic drugs. Other drugs like leflunomide, tofacitinib and several biological should be discontinued because pregnancy experience is at present insufficient and safety for the fetus has not been proven.Flares of rheumatic disease showing be treated immediately and with pregnancy compatible drugs.For patients with inflammatory arthritis like rheumatoid arthritis,spondyloarthritis and juvenile idioipathic arthritis disease activity during pregnancy can be controlled with antimalarials, sulfasalazine and TNF inhibitors. Women with systemic lupus erythematosus should continue basic therapy with hydroxychloroquine, and azathioprine, ciclosporine or tacrolimus added when necessary due to organ manifestations. Severe flares during pregnancy may require biologics like rituximab,abatacept,tocilizumab or Anakonda, in SLE corticoid pulses or, if life threatening, intravenous gamma globulin or cyclophosphamide. Treatment during pregnancy demands balancing suppression of maternal disease and no harm to the child. Selecting the adequate type, the right dose and the right timing of medications for optimal care of pregnant patients remains a challenge. <h3>Disclosure of Interest</h3> None declared
OP0175 Characterization of novel stromal-derived autoantigens recognized by ra synovial monoclonal antibodies
Authors: E Corsiero, L Jagemann, E Prediletto, C Pitzalis, M Bombardieri
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> We previously showed that up to 40% of RA synovial recombinant monoclonal antibodies (RA-rmAbs) generated from germinal center-like structure (GC-LS+) RA synovium recognize citrullinated antigens contained in neutrophils extracellular traps (NET) (1). The cellular source of other potential autoantigens targeted by the majority of locally differentiated B cells remains undefined. Recently, RA-fibroblast-like synoviocytes (RA-FLS) have been implicated in the release of citrullinated antigens (2, 3). However, whether these cells are targeted by RA-rmAbs is still unknown. <h3>Objectives</h3> Here, we aimed to define the RA-rmAbs immunoreactivity towards i) RA-FLS and ii) identify potential stromal-derived autoantigens. <h3>Methods</h3> 67 RA-rmAbs were generated from single CD19+ B cells FACS-sorted from fresh synovial cell suspensions following IgV<sub>H</sub>+V<sub>L</sub> genes cloning (1). RA-rmAbs were tested by means of i) cell-based immunofluorescence assays with FLS of RA patients and controls (osteoarthritis (OA)-FLS and RA-dermal fibroblast (RA-DF)), ii) co-localization with stromal specific markers and iii) immunoenzymatic tests with co-localizing antigens. Control rmAbs were also used (Sjögren9s syndrome/healthy donor-IgG rmAbs). <h3>Results</h3> Immunofluorescence on RA-FLS demonstrated reactivity of 21% of RA-rmAbs (14/67 rmAbs) towards cytoplasmic components of FLS. Only 4 rmAbs out of 14 were binding both FLS and NET components. For some rmAbs this reactivity was not specific to RA-FLS since it was also observed for OA-FLS and RA-DF. Interestingly, strong co-localization was observed with calreticulin (CRT) which in its citrullinated (cit-CRT) form has been previously shown to recognize the RA "shared epitope" HLA domain sequence (3). When tested in ELISA for native vs cit-CRT, 57% (8/14 rmAbs) of the FLS-reactive RA clones showed binding to CRT with 4 out of 8 rmAbs displaying increased immunoreactivity towards cit-CRT. Controls rmAbs showed no reactivity to either FLS or CRT. Preliminary data suggest that RA patient serum preferentially recognize the lectin-like N-terminal domain of CRT (4). <h3>Conclusions</h3> Here, we provide novel evidence that a subset of locally differentiated B cells within RA synovial GC-LS can react towards RA-FLS derived antigens. Preliminary data suggest that part of this reactivity is directed towards CRT. Identification of immunodominant epitopes within CRT is under investigations. <h3>References</h3> Corsiero et al, ARD 2015. Sorice et al, Rheumatology 2016. Ling et al, AR 2013. Hong et al, JI 2010. <h3>Disclosure of Interest</h3> None declared
Economic Burden of Acute Graft-Versus-Host Disease (GvHD) Following Allogeneic Hematopoietic Cell Transplant (HCT) for Hematologic Malignancies
Authors: Walter W Grubb, Samuel Huse, Naufil Alam, Samuel Dychter, John R. Wingard, Navneet S. Majhail, Ariel Berger
Journal: Blood (2016)
FRI0492 Obesity is highly overrepresented among swedish patients with psoriatic arthritis compared with the general population
Authors: E Klingberg, A Bilberg, B Eliasson, I Larsson
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patients with psoriatic arthritis (PsA) are at increased risk of developing cardiovascular disease. <h3>Objectives</h3> To determine the prevalence of cardiovascular risk factors among patients with PsA followed at a Swedish Rheumatology Clinic in comparison with the general population (GP). <h3>Methods</h3> A questionnaire including weight, height, smoking habits, hypertension, diabetes and hyperlipidemia was sent to all PsA patients registered at the Rheumatology Clinic at Sahlgrenska University Hospital, Gothenburg (N=982). Obesity was defined as body mass index (BMI) ≥30 kg/m<sup>2</sup>. Comparison with the Swedish GP was made using data from the National public health survey, "Health on equal terms", which is sent yearly to 20 000 citizens by the Public Health Agency of Sweden. <h3>Results</h3> 686 (70%) of the PsA patients with mean age 56±11yrs (mean: SD), 52% women, responded.Higher prevalence of self-reported obesity and several cardiovascular risk factors was found in the PsA patients compared with the GP: Obesity 28.7% [GP 15% (95% C.I. 14.5–15.9%)], current smoking 10.5% [GP 9% (8.2–9.3%)], former smoking 43.4% [GP 23% (22.3–24.0%)], never smoking 48.8% [GP 63% (61.9–63.9%)], treatment of hypertension 32.9% [GP 20% (19.6–21.2%)] and diabetes 8.3% [GP 6% (5.4–6.3%)] Treatment of hyperlipidemia was reported by 15.0% [GP no data] and overweight by 36.2% [GP 36% (34.5–36.5%)]. Data stratified by age and sex is shown in the table. (Numbers are % and 95% C.I.) <h3>Conclusions</h3> Obesity was highly overrepresented among the PsA patients. It is imperative to take action against weight gain in overweight patients and promote weight loss in obese patients with PsA, since obesity may be involved in the pathogenesis of the disease and may fuel disease activity. <h3>Disclosure of Interest</h3> None declared