S.-H. Park

Urine β2-microglobulin is associated with clinical disease activity and renal involvement in female patients with systemic lupus erythematosus

Objective We investigated the association of serum and urine β2-microglobulin (β2MG) with renal involvement and clinical disease activity in systemic lupus erythematosus (SLE). Methods Sixty-four female patients with SLE were enrolled. We assessed SLE disease activity (SLEDAI)-2K and measured serum and urine β2MG levels, as well as complement (C3 and C4) and anti-dsDNA levels. According to the SLEDAI scores, two groups were categorized: low (0–5 of SLEDAI) and high (6–19 of SLEDAI) disease activity groups. The presence of renal involvement was determined by renal SLEDAI score. Statistical analysis was performed using Spearman’s correlation analysis, Mann-Whitney U test, multivariate regression analysis, and logistic regression analysis. Results Urine β2MG levels were significantly different between low and high SLEDAI groups (p = 0.001), but not for serum β2MG levels (p = 0.579). Patients with renal involvement showed higher urine β2MG levels compared to those without renal involvement (p < 0.001), but again there was not a difference in serum β2MG levels (p = 0.228). Urine β2MG was closely associated with SLEDAI (r = 0.363, p = 0.003), renal SLEDAI (r = 0.479, p < 0.001), urine protein/Cr (r = 0.416, p = 0.001), and ESR (r = 0.347, p = 0.006), but not serum β2MG (r = 0.245, p = 0.051). Urine β2MG level was identified as a surrogate for renal involvement (p = 0.009, OR = 1.017, 95% CI 1.004–1.030) and overall disease activity (p = 0.009, OR = 1.020, 95% CI 1.005–1.036). Conclusions We demonstrated that urine β2MG levels are associated with renal involvement and overall clinical disease activity in SLE.

Pain, xerostomia, and younger age are major determinants of fatigue in Korean patients with primary Sjögren’s syndrome: a cohort study

Objectives: Fatigue is a common clinical manifestation in patients with primary Sjögren’s syndrome (pSS). The aims of this study were to investigate the association between fatigue severity and other clinical characteristics in pSS patients and to determine the factors contributing to fatigue. Method: We analysed 257 participants from the Korean Initiative of pSS (KISS), a prospective pSS cohort. Fatigue was assessed according to the fatigue domain of the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Patient-Reported Index (ESSPRI). Health-related quality of life (HRQoL) was evaluated using the EuroQol-5 dimensions (EQ-5D) questionnaire. Multiple linear regression analysis was used to estimate the effect of each variable on fatigue severity. Results: The median total ESSPRI score was 5 [interquartile range (IQR) 4–6]. Thirty-four per cent of patients reported a fatigue score > 5. Younger and premenopausal patients presented with more fatigue (p = 0.013 and p < 0.001, respectively). Higher Xerostomia Inventory (XI) scale (p < 0.001) and Ocular Surface Dryness Index (OSDI) (p < 0.001) scores were observed in patients with a fatigue score > 5. Pain, xerostomia, and age were determined to be significantly associated with fatigue severity after adjusting for depression/anxiety, OSDI score, and the presence of fibromyalgia using a multivariate general linear model. The ESSPRI fatigue score was correlated with the EQ-5D by time trade-off (TTO) values and visual analogue scale (VAS) scores. Conclusions: In Korean patients with pSS, younger age, xerostomia, and pain were correlated significantly with fatigue, and fatigue was associated with HRQoL.

Salivary gland ultrasonography findings are associated with clinical, histological, and serologic features of Sjögren's syndrome.

Objective: Salivary gland ultrasonography (SGUS) has been applied in the diagnosis of Sjögren’s syndrome (SS). The aim of this study is to investigate the association of SGUS findings with clinical, histological, and serologic features of SS. Methods: A total of 104 patients with suspected SS underwent SGUS for evaluation of salivary gland involvement. Patients with primary SS were determined according to the classification criteria for SS. The parenchymal inhomogeneity of bilateral parotid and submandibular glands was graded from 0 (homogeneity) to 4 (gross inhomogeneity). Receiver operating characteristic curve analysis was performed to compare the diagnostic performance of different SGUS scoring methods. Clinical and serologic features were compared between groups classified by SGUS score. The association between SGUS and these features of SS was explored by multivariable linear regression analysis. Results: Study participants were predominantly women (96.2%) and had a mean age of 54.1 years. Eighty-seven patients and 88 patients with primary SS were identified based on AECG criteria and ACR/EULAR classification criteria for SS, respectively. Among the different scoring methods, the sum of the grades of four salivary glands (range 0–16) had the best diagnostic performance, with sensitivity of 77.3% and specificity of 87.5% (cutoff value, 7) for distinguishing primary SS from sicca non-SS. SGUS score was associated with focus score in labial salivary gland biopsy (β = 0.240, p = 0.033) and anti-Ro/SSA serology (β = 0.283, p = 0.016) and inversely associated with unstimulated whole salivary flow (β = −0.298, p = 0.011). Conclusion: Ultrasonography of major salivary glands is associated with histopathology of minor salivary glands, serology of SS, and salivary gland function.

AB0627 Physical activity by self-reported physical activity and lupus nephritis in patients with systemic lupus erythematosus

Background Physical activity is found to be associated with clinical status such as disease activity, organ damage, disability, fatigue, and quality of life in systemic lupus erythematosus (SLE). Objectives The aim of this study was to identify the association between physical activity and disease activity and organ damage in patients with SLE. Methods A total of 415 patients with SLE were consecutively enrolled from KORean lupus Network (KORNET) registry. This registry assessed clinical features, disease activity Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K]), and disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology [SLICC/ACR] damage index [SDI]) at the enrollment of study. Self-reported physical activity was measured by International Physical Activity Questionnaire (IPAQ). Statistical analyses were used by Mann-Whitney U test and multivariate logistic regression analysis. Results There is significant difference of vigour activity between patients with lupus nephritis (n=93) and without lupus nephritis (n=322) (p=0.012), but not moderate and walking activities. In contrast, the differences of each physical activity, walking, moderate, and vigorous intensity, according to SLEDAI-2K and SDI were not found. In addition to high PCS of SF-36 (p=0.006) and SLEDAI-2K (p=0.038), less vigorous physical activity were related with lupus nephritis (p=0.033). However, the risk of CVD was not associated with physical activity of SLE. Conclusions This study showed that patients with lupus nephritis had less vigorous physical activity. It implicates that SLE-related organ damage might be associated with levels of physical activity. References [1] Costenbader KH, Wright E, Liang MH, Karlson EW. Cardiac risk factor awareness and management in patients with systemic lupus erythematosus. Arthritis Rheum2004;51:983–8. [2] Katz P, Julian L, Tonner MC, Yazdany J, Trupin L, Yelin E, Criswell LA. Physical activity, obesity, and cognitive impairment among women with systemic lupus erythematosus. Arthritis Care Res (Hoboken)2012;64:502–10. Disclosure of Interest None declared

AB0077 High-mobility group box 1 mediated monosodium urate crystal-induced nlrp3 inflammasome activation in human macrophages

Background High-mobility group box 1 (HMGB1) was identified originally as a highly conserved non-histone DNA-binding factor and recently noted as a potent inflammatory mediator under inflammatory conditions. Objectives This study is to investigate the inflammatory cascade between HMGB1 protein and activation of NLRP3 inflammasome in human macrophage under uric acid-induced inflammation. Methods The study used human U937 macrophage cell line under stimulation with monosodium urate (MSU) crystal or HMGB1. Total reactive oxygen species (ROS) were measured by flow cytometry. Interleukin-1b (IL-1b), NLRP3, TXNIP, HMGB1, NF-kB, IkBa, and caspase-1 protein expression was detected using western blotting. IL-1b, IL-18, caspase-1, and HMGB1 gene expression were assessed by quantitative real-time polymerase chain reaction. Intracellular HMGB1 expression was assessed by immunofluorescent staining with MitoTracker Red. Results MSU crystals induced HMGB1 and ROS production by activation of NF-kB signal pathway in human macrophages. HMGB1 mRNA expression was markedly attenuated under stimulation using TXNIP siRNA. Enhanced release of IL-1 was noted through increased HMGB1 expression and TXNIP-mediated NLRP3 infammasome activation under stimulation of MSU. Combination of MSU and HMGB1 augmented NLRP3 inflammasome, compared to either MSU or HMGB1 stimulation. Conclusions This study demonstrated that HMGB1 is a crucial molecule for ROS-mediated TXNIP and NLRP3 inflammasome activation in uric acid-induced inflammation. Disclosure of Interest None declared

Effect of alcohol consumption and smoking on disease damage in systemic lupus erythematosus: data from the Korean Lupus Network (KORNET) registry:

Background We assessed correlations of smoking habits and alcohol consumption with disease activity or damage in patients with systemic lupus erythematosus (SLE). Methods A total of 505 patients with SLE were enrolled in the Korean Lupus Network (KORNET) SLE registry from January 2014 to January 2016. Disease activity and organ damage were measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index, respectively. Multivariate logistic regression analysis was used to analyze associations with cutaneous lesions. Results There were no differences in SLEDAI-2K and SLICC/ACR damage indices according to either smoking status or alcohol consumption. More frequent cutaneous damage was observed in current alcohol drinkers compared with non-current alcohol drinkers (p = 0.020). Cutaneous damage was significantly associated with alcohol consumption (odds ratio (OR) 4.048, 95% confidence interval (CI) 1.251–12.102, p = 0.020). Both low (1–5 glasses/week) and high (≥6 glasses/week) amounts of alcohol consumption had a significant impact on cutaneous damage compared with the absence of current alcohol consumption (p = 0.033 and p = 0.027, respectively). Pairwise comparison of alcohol consumption and smoking status with cutaneous damage showed that only alcohol consumption was significantly associated with the presence of cutaneous damage, compared with non-current alcohol consumption and non-current smoking (OR 3.513, 95% CI 1.130–10.920, p =0.030). Conclusions Current alcohol consumption, but not smoking, might influence the development of cutaneous damage in patients with SLE.

AB0326 Influence of nonsteroidal anti-inflammatory drugs on arterial stiffness in patients with rheumatic diseases

Background The association with adverse cardiovascular (CV) events and NSAIDs has been the topic of much debate. Objectives The aim of the present study was to investigate the effects of continuing NSAIDs therapy on predictable parameters for CV events. Methods We enrolled 155 patients with variable rheumatic diseases (95 rheumatoid arthritis, 49 systemic lupus erythematosus, 3 behçets disease, 3 gout, 5others.) who were free from established CV diseases and had taken cardiovascular function tests from June 2015 to June 2016. They were divided into two groups depending on whether or not to have taken NSAIDs therapy for at least 5 years: NSAIDs taking group (91 patients) vs. non NSAIDs taking group (64 patients). For evaluating heart function, transthoracic echocardiography was used. Arterial stiffness was assessed using brachial-ankle pulse wave analysis. Results There were no significant differences in blood pressure, serum creatinine, serum hemoglobin, total cholesterol, erythrocyte sediment rate, C-reactive protein, disease duration, age, and smoking history between the groups. The NSAIDs taking group had a higher median (95% Cl) baPWV (brachial-ankle pulse wave velocity) and median (95% Cl) mean pulmonary artery pressure (mPAP) than non-NSAIDs taking group: baPWV 13.72 (12.77–15.62) vs. 15.29 (13.93–17.63) m/s, p=0.005; mPAP 26.5 (22.8–30.5) vs. 30.5 (27.3–32.3) mmHg, p=0.011. But baPWV and mPAP were not significantly different between selective cyclooxygenase-2 inhibitor (22 patients) and nonselective NSAIDs (69patients): baPWV 15.33 (13.98–17.63) vs. 14.83 (13.82–17.39) m/s, p=0.191; mPAP 29.0 (24.5–34.5) vs. 30.0 (26.0–33.0) mmHg, p=0.960. Conclusions Our study suggests that continuing NSAIDs therapy is associated with increased arterial stiffness in patients with rheumatic diseases, independently noted to increase the incidence of cardiovascular disease. Disclosure of Interest None declared

AB0056 Downregulation of Tumor Necrosis Factor and Interleukin-1 by Ellagic Acid

Background Ellagic acid (EA) is a phenolic constituent in fruits and nuts, such as raspberries, strawberries, walnuts, mango kernel and pomegranate. It was documented that EA shows anti-fibrotic, anti-inflammatory activity in vivo model of bowel inflammation and lung fibrosis, however the precise mechanism of signal inhibition was not extensively investigated. Objectives The objectives of this study are first, to elucidate the anti-inflammatory effect of EA in RAW 264.7 murine macrophage cell line by NF-kB pathway in vitro, and second, to compare it with effect of other immuno-modulating agent, tacrolimus and colchicine. Methods We determined the cytotoxic effect of EA using MTT assay. The effects of EA on tumor necrosis facor (TNF)-alpha induced mRNA and protein expression were investigated using quantitative real-time PCR and western blot. In addition, we examined the effects of pharmaceutical drugs with anti-inflammatory properties on expression of TNF-alpha. Results EA significantly suppressed the expression of interleukin-1 beta and TNF-alpha in a dose dependent manner. EA suppressed TNF-alpha induced inflammatory genes expression by inhibiting the phosphorylation of JNK and Akt, whereas had no significant effect on p38 activation. In addition, the inhibitory effect of EA on TNF-alpha induced inflammatory genes expression was regulated by suppression of IkB-alpha phosphorylation and NF-kB translocation. The expression of TNF-alpha mRNA level was reduced comparably treated with EA and other anti-inflammatory agents (ascorbic acid, dexamethasone and colchicine). Conclusions These findings suggest that EA suppresses inflammatory genes expression through phosphorylation of JNK/Akt and regulation of NF-kB signal pathway in TNF-alpha induced inflammation. Further investigation regarding effects of EA on autoimmune, inflammatory is scheduled. References S. Corbett, J. Daniel, R. Drayton, M. Field, R. Steinhardt, N. Garrett, Evaluation of the anti-inflammatory effects of ellagic acid, J. Perianesth. Nurs. 25 (2010), 214–220. S. Ahmed, A. Rahman, M. Saleem, M. Athar, S. Sultana, Ellagic acid ameliorates nickel induced biochemical alterations: diminution of oxidative stress, Hum. Exp. Toxicol. 18 (1999) 691–698. Disclosure of Interest None declared

AB0293 Factors Influencing Physician Global Assessment of Rheumatoid Arthritis Disease Activity in Usual Clinical Practice

Background Patient global assessment (PATGL) and physician global assessment (PhGL) of disease status are 2 of the 7 rheumatoid arthritis (RA) core data set measures. Several reports indicate considerable discordance between PATGL and PhGL [1]. Variation in PhGL appears to be explained by different factors in discordant patient group comparing with concordant group. Objectives To analyze variation in PhGL by examination of possible associations with all RA core data set measures, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), in patients monitored in usual care in a Korean rheumatology setting. Methods A cross-sectional study was conducted of patients with RA seen by 4 rheumatologists in a Korean usual care setting. All core data set measures, as well as RF and ACPA, are collected in each RA patient. A tender joint count (TJC28) and swollen joint count (SJC28) are performed on each patient, and laboratory tests – erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), RF and ACPA – are obtained. A PhGL is assigned by the rheumatologist after review of all data. All study population was divided in three groups: positive discordance; PATGL-PhGL>1, no discordance; -1≤PATGL-PhGL≤1, negative discordance; PATGL-PhGL<-1. In each group, correlations of all core data set measures, as well as RF and ACPA, with PhGL were analyzed using Spearmans rho. Univariate and multivariate regressions were performed for each measure with PhGL as the dependent variable, and core data set measures and laboratory tests as independent variables. Results The study population was 89.2% female, with median age 55.0 years. PhGL was correlated significantly with all 7 core data set measures (Spearmans rho 0.236-0.356, p<0.001). PhGL was not correlated significantly with RF and ACPA. 270 patients (53.8%) were positively discordant and median disease activity score (DAS)28 was 3.9. TJC28, pain, PATGL, PhGL, DAS28 was significantly different between 3 groups. By multivariate regression, PhGL was associated independently with TJC28, PATGL and ESR in positive discordance group. TJC did not influence PhGL in concordant group. If a RF level was high, physicians seemed to rate disease activity higher than patients in negative discordant group. Conclusions PhGL is correlated significantly with all RA core data set measures. In multivariate regressions, PhGL was associated significantly with TJC28, PATGL, ESR and RF, but not with SJC28, physical function or pain score. These findings are consistent with other reports in the literature. Further research is needed to clarify the basis for variation in PhGL and concordance or discordance with PATGL. References Barton JL, Imboden J, Graf J, et al. Arthritis Care Res 2010;62:857-64 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3450

SAT0093 Association of Formal Education Level (EDUC) with Clinical Status in Korean Fibromyalgia (FM) Patients

Background Low formal education level (EDUC), an indicator of socioeconomic status, is an established risk factor to develop rheumatoid arthritis (RA) as well as many other diseases,1 and low EDUC is associated with poor clinical status in RA according to patient questionnaires, joint counts and laboratory tests.2 Formal studies of possible associations of EDUC with more severe status in FM have not been reported. The diagnosis of FM depends primarily on a patient history of extensive pain and other symptoms, so clinical status might be best addressed by patient-reported outcomes (PROs) on self-report questionnaires. Objectives To investigate possible associations of EDUC, as well as age, duration of disease (DUR) and body mass index (BMI), with PRO scores in Korean patients with FM. Methods Responses of Korean patients with FM on the widespread pain index (WPI), symptom severity scale (SS), fibromyalgia impact questionnaire (FIQ), and multidimensional health assessment questionnaire/routine assessment of patient index data (MDHAQ/RAPID3) were analyzed. Statistical significance was tested using Spearman correlations of PROS with EDUC, age, DUR and BMI. A series of multivariate regressions was computed for each PRO as a dependent variable, and for age, DUR, BMI and EDUC as independent variables. Results In univariate correlations (data not shown) EDUC was correlated significantly with WPI (rho=-0.41, p=0.01), SS (rho=-0.47, p<0.01), FIQ-symptoms (rho=-0.39, p<0.02), FIQ-total score (rho=-0.35, p=0.03) and MDHAQ pain (rho=-0.33, p=0.04), generally at higher levels than age, DUR or BMI with these variables. Age also was correlated significantly with FIQ-overall impact, FIQ-symptoms, FIQ-total score, MDHAQ-PATGL and RAPID3; DUR also was correlated significantly with FIQ-overall impact, FIQ-symptoms and FIQ-total score (data not shown). No significant correlations were seen with BMI. In multivariate regressions (Table), EDUC was significantly and independently associated with SS, FIQ-symptoms, FIQ-total score, MDHAQ pain, RAPID3. Age also was significant in regressions, generally at lower beta coefficients than EDUC; DUR and BMI were not significant (Table 1). Table 1. Beta coefficient (p value) of regressions including 4 possible independent variables to explain variation in PRO domains in FM PRO domain Independent variables, Beta coefficient (p value) R 2 Age DUR BMI EDUC WPI −0.17 (0.12) 0.21 (0.15) 0.28 (0.46) −0.55 (0.05) 0.29 SS −0.11 (0.04) 0.01 (0.96) 0.13 (0.49) −0.27 (<0.05) 0.25 FIQ-function −0.02 (0.11) 0.03 (0.77) 0.05 (0.84) −0.05 (0.75) 0.08 FIQ-overall impact −0.24 (<0.01) 0.14 (0.21) 0.21 (0.47) −0.17 (0.43) 0.29 FIQ-symptoms −1.07 (<0.01) 0.81 (0.11) 0.70 (0.59) −2.26 (0.02) 0.40 FIQ-total score −1.42 (<0.01) 0.97 (0.13) 0.96 (0.57) −2.48 (<0.05) 0.37 MDHAQ-function −0.04 (0.137) −0.01 (0.76) 0.11 (0.21) −0.07 (0.24) 0.17 MDHAQ-pain −0.14 (0.01) −0.01 (0.95) −0.23 (0.25) −0.38 (0.01) 0.29 MDHAQ-patient global −0.14 (0.02) −0.02 (0.77) 0.16 (0.41) −0.20 (0.15) 0.23 RAPID3 −0.31 (0.01) −0.04 (0.82) 0.04 (0.92) −0.66 (0.03) 0.27 Conclusions In patients with FM, many PROs are associated significantly with EDUC, generally at higher levels than with age, DUR or BMI. EDUC should be included in all studies of patients with FM, as well as other rheumatic diseases. References J Chronic Dis 1987;40:865-74. Arthritis Rheum 1988;31:1346-57. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3920