tbuckley/cabot-search huggingface dataset:
THU0022 Replication analysis of gene-gene interaction between HLA-DQA2 and HLA-DQB2 variants in italian rheumatoid arthritis patients
Authors: R Bassi Andreasi, MFJ Khan, E Galuppi, M Govoni, M Rubini
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid Arthritis (RA) is a complex and multifactorial disease, caused by multiple interactions between genetics and environmental factors. In the context of RA genetics, the Human Leukocyte Antigen (HLA) exerts a primary role. Approximately 90% of RA patients show alleles at the HLA-DRB1 locus, codifying for 5 Amino Acids, known as "<i>shared epitope</i>" (SE). SE is associated with increased risk to develop RA and more severe phenotype, but it does not entirely explain HLA contribution to disease risk. Moreover, it is generally accepted that occurrence risk could be determined by specific gene-gene interactions. A study carried out in USA (NARAC) reported a particular interaction between SNPs in the HLA class II region: HLA-DQA2 (rs9275595) and HLA-DQB2 (rs10807113). Results showed 11 fold increased risk to develop RA in patients carrying both variants (Liu <i>et al</i>., 2011), while single variants did not significant contribute to the RA risk (Odds ratio, OR, respectively, 1.6 and 1.0). Gene-gene interaction between HLA-DQA2 and HLA-DQB2 SNPs is remarkable, considering that glycoproteins codified by these genes combined each other and create a quaternary structure. <h3>Objectives</h3> To replicate NARAC study evidence in Italian population, we genotyped rs9275595 (HLA-DQA2) and rs10807113 (HLA-DQB2) variants using a case/control model. <h3>Methods</h3> The study included a cohort of 316 Italian RA patients and a matched group of 443 healthy control individuals. All subjects were genotyped for HLA-DQA2 T&gt;C (rs9275595) and HLA-DQB2 A&gt;C (rs10807113) using TaqMan technology and Real-Time PCR. <h3>Results</h3> Replication test performed in our Italian RA cohort did not identify significant interaction between two variants analyzed. However, considering the single variant rs9275595, the results showed a significantly increased risk to develop RA. Taking T/T genotype as the reference, C/C homozygotes showed significant association with a 3.82 fold increased risk of RA (OR=3.821 95% CI (2.017–8.351) p-value=0.00063). The SNP acted under an additive model: T/C heterozygotes showed significant OR=1.988 (95% CI 1.458–2.711, p-value=0.00002). <h3>Conclusions</h3> The results of this study do not confirm the gene-gene interaction previous reported in the NARAC cohort (Liu <i>et al</i>., 2011). However, outcomes suggest that HLA-DQA2 rs9275595 could contribute to RA pathogenesis in the Italian population. <h3>References</h3> Liu C, Ackerman HH, Carulli JP. A genome-wide screen gene-gene interactions for rheumatoid arthritis susceptibility. Hum Genet. 2011 May;129(5):473–85. <h3>Disclosure of Interest</h3> None declared
Topological organization and dynamic regulation of human tRNA genes during macrophage differentiation
Authors: Kevin Van Bortle, Douglas H. Phanstiel, Michael P. Snyder
Journal: Genome biology (2017)

The human genome is hierarchically organized into local and long-range structures that help shape cell-type-specific transcription patterns. Transfer RNA (tRNA) genes (tDNAs), which are transcribed by RNA polymerase III (RNAPIII) and encode RNA molecules responsible for translation, are dispersed throughout the genome and, in many cases, linearly organized into genomic clusters with other tDNAs. Whether the location and three-dimensional organization of tDNAs contribute to the activity of these genes has remained difficult to address, due in part to unique challenges related to tRNA sequencing. We therefore devised integrated tDNA expression profiling, a method that combines RNAPIII mapping with biotin-capture of nascent tRNAs. We apply this method to the study of dynamic tRNA gene regulation during macrophage development and further integrate these data with high-resolution maps of 3D chromatin structure. Integrated tDNA expression profiling reveals domain-level and loop-based organization of tRNA gene transcription during cellular differentiation. tRNA genes connected by DNA loops, which are proximal to CTCF binding sites and expressed at elevated levels compared to non-loop tDNAs, change coordinately with tDNAs and protein-coding genes at distal ends of interactions mapped by in situ Hi-C. We find that downregulated tRNA genes are specifically marked by enhanced promoter-proximal binding of MAF1, a transcriptional repressor of RNAPIII activity, altogether revealing multiple levels of tDNA regulation during cellular differentiation. We present evidence of both local and coordinated long-range regulation of human tDNA expression, suggesting the location and organization of tRNA genes contribute to dynamic tDNA activity during macrophage development.
SAT0107 Factors that influence on pain control during treatment for rheumatoid arthritis patient
Authors: I Yoshii, T Chijiwa
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Pain control is the most important theme for treatment of rheumatoid arthritis (RA) patient. For pain control, it is obviously important key to control disease activity control. However, patient status at start of treatment (BL), can be also important as well as disease activity control. Including these factors, keys that can reduce pain should be clarified. <h3>Objectives</h3> In this study, factors that affect on pain control were evaluated statistically from real clinical data. <h3>Methods</h3> In 685 RA patients who have been treated for more than 1 year, 500 patients were monitored their disease activity with parameters in 28-joints disease activity index with C-reactive protein (DAS28-CRP), pain score with using visual analogue scale (PS-VAS), modified Health Assessment Questionnaire Disability Index (mHAQ). Drugs administered for patient had been checked at the time of consult. PS-VAS at consult was evaluated, as it demonstrated no more than 15mm, or decrease than last time more than 20mm was evaluated as "Pain Reduced". Patients sex, ACP, Sharp/van der Heijde Score (SHS), patients current age, history length, DAS28-CRP and its components, PS-VAS at BL, and followed consultation, drug usage and its dosage were evaluated for Pain Reduced statistically with Binary Logistic Regression Analysis. Significant level was set within 1%. <h3>Results</h3> 14,005 times from 495 patients were enrolled in this study. At BL, male patient, higher ACPA, younger age at onset and at BL, older age at following consultation, short following term, smaller SvdHS, greater tenderness joint count (TJC), swollen joint count (SJC), smaller patient9s global assessment (PGA), evaluator9s global assessment (EGA), great CRP, and smaller mHAQ and DAS28-CRP at BL demonstrated significant contribution on Pain Reduce. In following consult, smaller mHAQ, PS-VAS, and DAS28-CRP, in which smaller PGA and EGA, demonstrated significant contribution on Pain Reduce. In drugs, paraetamol/tramadol combination drug use, non-steroid anti-inflammation drug (NSAIDs) use, pregabalin use, tofacitinib use, and opioid use, and methotrexate dose decrease demonstrated significant contribution on Pain Reduce. <h3>Conclusions</h3> These results suggest that pain control for RA patient depends on patient9s status at baseline. And followed disease activity control and activity in daily life (ADL) maintenance. In adding with these, drug selection is also important key. It is also suggested specific drugs have higher effect on pain control. Anti-chronic pain agent can be candidate for pain relief for the patient who complains remnant pain even after successful disease activity control and ADL maintenance. <h3>Disclosure of Interest</h3> None declared
OP0287 Ultrasonography-detected peripheral enthesitis in patients with axial spondyloarthritis – anatomical distribution, morphology and response to anti-tnf therapy
Authors: S Seven, SJ Pedersen, M Østergaard, IJ Sørensen, UM Døhn, S Krabbe, L Terslev
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Peripheral enthesitis (PE) is a characteristic feature of spondyloarthritis (SpA) that may be asymptomatic and only detectable by imaging. Ultrasonography (US) has greater sensitivity than clinical examination for the detection of PE.[1] <h3>Objectives</h3> The aim of the study was to investigate the anatomical distribution, morphological abnormalities and response to anti-tumor necrosis factor (anti-TNF) therapy of US-detected PE in patients with axial SpA (axSpA) initiating adalimumab (ADA). <h3>Methods</h3> In a randomized, placebo-controlled, double-blinded investigator-initiated trial (NCT01029847), patients with axSpA according to the Assessment of SpA International Society (ASAS) criteria were randomized to subcutaneous ADA 40 mg every other week (eow) or placebo from baseline to week 6. From week 6 to 24, all patients received ADA 40 mg eow. Of 49 patients enrolled, 21 participated in the US sub-study. US assessment applying the OMERACT US definitions for enthesitis[2] of 10 peripheral entheseal regions (Tables 1 &amp; 2) and clinical examination were performed at baseline, weeks 6 and 24. US was performed by an experienced investigator. Hypo-echogenicity, increased thickness and Doppler activity of the enthesis were considered signs of active inflammation, whereas insertional bone erosions, intratendinous calcifications and enthesophytes were regarded as signs of chronic lesions.[2] <h3>Results</h3> See tables. <h3>Conclusions</h3> In this axSpA cohort, US assessment primarily identified PE in the lower extremities, and predominantly chronic lesions. No change in chronic PE lesions were found during treatment indicating a low sensitivity to change of these lesions. The number of entheses with inflammatory activity was too low to detect any changes on US during ADA therapy. <h3>References</h3> D9Agostino MA, et al. Ann Rheum Dis 2011, 70(8):1433–1440. Terslev L, et al. Arthritis Care Res (Hoboken) 2014, 66(5):741–748. <h3>Disclosure of Interest</h3> None declared
FRI0302 Elevated cysteine-rich protein 61 in systemic lupus erythematosus-associated pulmonary arterial hypertension
Authors: Y Fan, J Qian, Y Hao, M Li, L Gao, X Zeng, Z Zhang
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Pulmonary arterial hypertension (PAH) is a complex and devastating complication of connective tissue diseases that leads to severe morbidity and mortality.Unlike in Caucasians, it is systemic lupus erythematosus that recognized as the the major underlying cause of CTD associated PAH in Asian countries, especially in China [1]. Early diagnosis and intervention is vital for better long-term outcome in SLE-PAH patients.Previous study has demonstrated Cysteine-rich protein 61 (Cyr61) was highly expressed in SLE patients [2].However,the role of Cyr61 in pulmonary arterial hypertension (PAH) remains unknown. <h3>Objectives</h3> To explore the value of Cyr61 for PAH in SLE patients by comparing the plasma Cyr61 levels in SLE patients with/without PAH. <h3>Methods</h3> Plasma samples from two tertiary medical centers were obtained from 54 patients with definite SLE-PAH, 52 age,gender and SLEDAI matched SLE patients without PAH, and 54 age and gender matched healthy controls. Plasma Cyr61 concentration was measured by enzyme-linked immunosorbent assay. <h3>Results</h3> Plasma Cyr61 concentration in SLE-PAH patients was significantly higher than the matched SLE patients and healthy controls (median (IQR): 172.5 (143.8, 218.2), 124.9 (104.1, 154.7), 58.17 (28.9, 80.4) respectively, P&lt;0.001) (Figure1). The sensitivity and specificity of Cyr61 in predicting the presence of PAH in entire SLE patients were 79.6% and 67.3%. Receiver operating characteristic curve analysis showed the area under the curve was 0.757 (95% CI: 0.662–0.852), with 140.6 pg/ml as the cut off concentration (Figure2). Further multivariate logistic regression analyses revealed high Cyr61 level (&gt;140.6) is an independent risk factor for SLE patients to develop PAH (OR:7.822 (95% CI: 2.224–41.138)) (Table 1). Additionally, weak to moderate positive correlations were observed between Cyr61 concentration and serositis, hematological involvement, red blood cell distribution width, right ventricular systolic pressure and right ventricular diameter measured by echocardiography in entire SLE population. <h3>Conclusions</h3> Plasma Cyr61 level was significantly higher in SLE-PAH patients than SLE patients without PAH. Cyr61 may be used as a biomarker for PAH complication in SLE patients. <h3>References</h3> Hao, Y.J., et al., Connective tissue disease-associated pulmonary arterial hypertension in Chinese patients. European Respiratory Journal, 2014. 44(4): p. 963–972. Lin, J., et al., Serum Cyr61 is associated with clinical disease activity and inflammation in patients with systemic lupus erythematosus. Medicine (Baltimore), 2015. 94(19): p. e834. <h3>Disclosure of Interest</h3> None declared
AB0665 Association between microvaculature changes and pulmonary involvement in systemic sclerosis: a follow-up study
Authors: R Bečvář, M Tomčík, J Štork, A Slováková
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Lung involvement is the major cause of mortality in patients with systemic sclerosis (SSc). Gas transfer (DLCO) and FVC levels have traditionally been used as measures of disease severity and reductions of both parameters have been associated with increased mortality. In SSc repeated attacks of Raynaud9s phenomenon lead to the reduced capillary density leads with reduced blood flow and tissue ischemia. Raynaud9s phenomenon can occur also in the lungs. Tissue hypoxia usually initiates the formation of new blood vessels from the pre-existing microvasculature. Nailfold capillaroscopy is a safe, noninvasive routine way for the microvascular investigation. <h3>Objectives</h3> The aim of this study was to assess the correlation between capillaroscopic abnormalities and parameters of interstitial lung involvement at baseline and after one year follow-up in patients with SSc. <h3>Methods</h3> All patients underwent routine clinical examination (dyspnea, cough, crepitus), pulmonary function tests, DLCO (alveolitis grade and fibrosis), blood gases and HRCT scan of chest (1). Microvasculature changes were assessed using nailfold videocapillaroscopy (NVC) which was performed by two independent examiners. The obtained images were analysed anonymously by two investigators blinded for the clinical and serum status of SSc patients and classified as early, active and late pattern, non specific or normal picture (2). For statistical evaluation Poisson9s correlation coefficient and T-test were used. All examinations were performed at baseline and after 12 months. <h3>Results</h3> Total 42 patients (38 females) were investigated: 30 individuals with limited form, 7 with diffuse form, 3 patients with scleroderma sine scleroderma, 1 with overlap syndrome and 1 with undifferentiated connective tissue disease. The mean age ± standard deviation (SD) of the whole cohort was 51±22 years and the mean disease duration ± SD was 10±7 years. 3 patients (7.5%) had early NVC pattern, 12 patients (30%) had active, 10 (58%) late pattern, and 17 (37.5%) had nonspecific changes or normal picture. The patients with late NVC pattern exhibited more often mild to moderate alveolitis, decreased FEV1 and FVC and DLCO. When correlating NVC patterns with clinical findings, pulmonary function test and HRCT scans we found only an association of low significance with dyspnea and alveolitis grade (both p&lt;0.1). After one year follow-up similar results were obtained (p&lt;0,001 and p&lt;0,01, respectively). <h3>Conclusions</h3> In our study NVC patterns did not seem to correlate with severity of interstitial lung disease in SSc patients even after one year follow-up. <h3>References</h3> Corrado A et al. Joint Bone Spine. 2010. Cutolo M et al. J Rheumatol. 2000. <h3>Acknowledgements</h3> This study was performed with support of CMH Research Projects No 00000023728. <h3>Disclosure of Interest</h3> None declared
AB1015 Automated squeeze test (gaenslen's compression maneuver) in rheumatoid arthritis patients. exploratory study
Authors: D Vega-Morales, JA Esquivel-Valerio, AC Arana-Guajardo, MA Garza-Elizondo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The squeeze test (a.k.a Gaenslen9s Compression Maneuver) consists on the compression of the metacarpal-phalangeal (MCP) joints to elicit pain in a patient with active synovitis. The squeeze test has three main purposes: Screening of inflammatory arthritis, as a predictor of rheumatoid arthritis in arthralgia patients, and as a quick and practical evaluation of the presence/absence of synovitis in patients already diagnosed with RA. The force and the way to perform the squeeze test had been evaluated in rheumatologists on a biomechanical device, with conflicting results. We developed a biomechanical device to perform the squeeze test. <h3>Objectives</h3> Our aim is to determine the force whether the automated squeeze test discriminate patients with active RA from inactive ones. And the force that differentiates a healthy patient from a RA patient. <h3>Methods</h3> Observational study in RA (ACR/EULAR 2010) patients and healthy persons. We perform 3-squeeze test on the device in the MCP joints and record the force enough to elicit pain. And then compare them with the joint counts by the clinician <h3>Results</h3> Two hundred MCP joints from 50 hands were tested. From 25 RA patients with a mean age of 54.6 years (SD 11.22), with a mean disease latency of 1.2 years (SD 2.7). The total swollen joint count was 16 (7 right joints + 9 left joints) and 70 total tender joint count (30 right joints and 40 left joints). The median of force that caused pain in the RA patient9s right hand was 3.07 kg (IQR 2.4) and the left hand was 2.78 kg (IQR 3.8). The cut-off for the force to detect a tender right hand joint was 1,020 grams with a sensitivity of 100% and specificity of 10%; for a swollen right hand joint was 1,400 with a sensitivity of 100% and specificity of 28.6%. For a tender left hand joint was 1620 grams with a sensitivity 70% and specificity of 6.7%; and for a swollen left joint was 1990 grams with a sensitivity of 100% and specificity of 27.3%. In the second phase, 560 MCP joints of 140 hands from 70 healthy volunteers were compressed. The median force to elicit pain in the right hand was 4.2 kg (IQR 9.5) vs. 3.07 kg (IQR 8.7) from RA patients (p=0.003). And for left hand 4.6 kg (IQR 9.7) vs. 2.78 kg (IQR 9.2) from RA (p=0.014). <h3>Conclusions</h3> It is necessary to continue the exploration of the maneuver in different clinical settings. Validate the strength in patients with different arthropathies, activity levels and different clinical stages (screening, activity, prediction) and also with imaging methods for evidence of inflammation (US, MRI) <h3>Disclosure of Interest</h3> None declared
THU0399 Tapering therapy of tnf-inhibitor for mri changes in spondyloarthritis
Authors: Y Song, Y Cui, X Zhang, H Zeng, Y Zeng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> TNF-inhibitors could significantly improve disease activity of SpA patients, however, there is still no answer to the effect of prolonged the interval of TNF-inhibitors on MRI changes. <h3>Objectives</h3> The aim of the study was to investigate whether prolonged the interval of TNF-inhibitor injection could maintain SpA at low disease activity and improve imaging changes of sacroiliac joint. <h3>Methods</h3> A total of 98 SpA patients were included and 67 of them received TNF-i with or without conventional DMARDs. TNF-i included Etanercept, Infliximab and Adalimumab. The full dosage treatment was defined as patients received Etanercept 50 mg per week, Infliximab 4 mg/kg at 0, 2, 6 week and Adalimumab 40 mg every two weeks. The dose of Etanercept was gradually reduced to 50 mg every two weeks, 50 mg every three weeks and then 50 mg per month. The infusion of Infliximab was reduced to every 8 weeks, every 12 weeks and then every 16 weeks. The interval of Adalimumub injection was changed from 3 weeks to 4 weeks and then to two months. After full dose treatment in the first 3 months, patients who administrated TNF-i were evaluated every 3–6 months. According to laboratory tests including ESR, CRP and IgA levels, BASDAI, BASFI, ASDAS results and sacroiliac joint SPARCC scores, the interval of TNF-i treatment was prolonged gradually. Fat metaplasia, bone erosion, sclerosis and ankylosis changes on MRI were compared between baseline, 4–6 months and 1–2 years. <h3>Results</h3> After 3 months of treatment, inflammatory indexes, BASDI, BASFI, ASDAS and SPARCC scores were significantly lower than baseline (<i>P</i>&lt;0.05). After 4–6 months of treatment, ESR, CRP and IgA levels were greatly lower than before (8 (3,25) <i>vs</i>. 2 (1,3) mm/h, 4.97 (1.83,14.5) <i>vs.</i> 1.71 (1.24,2.82) mg/l, 2.96±1.34 <i>vs.</i> 2.20±1.01mg/l, Table 1, <i>P</i>&lt;0.01). Compared to baseline, significant reduction of BASDAI and BASFI score was observed in TNF-inhibitor group. The SPARCC scores in TNF-i group also decreased significantly (Figure1, <i>P</i>&lt;0.01). There was no significant progress in fat metaplaisa, bone erosions, sclerosis and ankylosis during the follow-up period (<i>P</i>&gt;0.05). Even though the inflammatory indexes and clinical evaluation of non-TNF-i group did not improved remarkably, SPARCC score were significantly reduced at 4–6 months and 1–2 years (<i>P</i>&lt;0.05). <h3>Conclusions</h3> TNF-i could reduce clinical and imaging inflammatory degree. Prolonged the interval of TNF-i treatment could maintain low disease activity and improve bone marrow edema, whereas fat metaplasia, bone erosion, sclerosis and ankylosis were not exacerbated. <h3>Disclosure of Interest</h3> None declared