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Featured researches published by E.H. Kang.


Scandinavian Journal of Rheumatology | 2014

The association of radiographic progression with serum R-spondin 1 (RSPO1) levels or Dickkopf-1 (DKK1)/RSPO1 ratios in rheumatoid arthritis patients: clinical evidence for reciprocal inhibition between DKK1 and RSPO1

Choi By; Chang Sh; Hyon Joung Cho; E.H. Kang; Kwangsoo Shin; Y.W. Song; Yun Jong Lee

Objectives: To investigate the clinical implications of serum levels of R-spondin 1 (RSPO1), a natural antagonist for Dickkopf-1 (DKK1), and of DKK1/RSPO1 ratios in rheumatoid arthritis (RA) patients. Method: Serum DKK1 and RSPO1 levels were measured in 102 RA patients and 39 age- and gender-matched healthy controls. In addition, DKK1 and RSPO1 levels were determined prior to and 3 months after anti-tumour necrosis factor alpha (anti-TNF-α) therapy in 15 RA patients. Clinical and laboratory data and baseline radiographs of the hands and feet were obtained. Serial radiographs were evaluated in 83 RA patients. Radiographic joint damage was assessed by the modified Sharp/van der Heijde score (SHS). Results: Serum RSPO1 levels were significantly reduced whereas serum DKK1 levels and DKK1/RSPO1 ratios were significantly increased in RA patients compared with controls (all p < 0.0001). Anti-TNF-α treatment significantly suppressed DKK1/RSPO1 ratios (p < 0.01). In contrast to DKK1 or RSPO1 levels, the ratios were significantly associated with erosive disease, elevated acute phase reactants, Disease Activity Score in 28 joints (DAS28) > 3.2, and radiographic progression rate (all p < 0.05). Although the RA patients with radiographic progression exhibited significantly increased DKK1 and reduced RSPO1 levels (p < 0.05), only the DKK1/RSPO1 ratio (log-transformed) was found to be a significant predictor of subsequent radiographic progression [odds ratio (OR) 2.07, p < 0.01]. Conclusions: In this study, the presence of RSPO1 in the circulation was shown for the first time. Our results suggest that the serum DKK1/RSPO1 ratio represents a better predictor of structural progression than either DKK1 or RSPO1 levels alone in RA patients.


Clinical Therapeutics | 2016

Efficacy and Tolerability of GCSB-5 for Hand Osteoarthritis: A Randomized, Controlled Trial

Jin Kyun Park; Kichul Shin; E.H. Kang; You Jung Ha; Yun Jong Lee; Kyung Hee Lee; Eun Young Lee; Yeong Wook Song; Yunhee Choi; Eun Bong Lee

PURPOSE The aim of this study was to investigate the efficacy and tolerability of GCSB-5, a mixture of 6 purified herbal extracts, in treating hand osteoarthritis (OA). METHODS A randomized, double-blind, placebo-controlled trial enrolled 220 patients with hand OA who had baseline a visual analog scale joint pain score of >30 of 100 mm at 3 hospitals between September 2013 and November 2014. After randomization, patients were allocated to receive oral GCSB-5 600 mg or placebo, bid for 12 weeks. The primary end point was the change in the Australian/Canadian OA Hand Index (AUSCAN)-defined pain score at 4 weeks relative to baseline. Secondary end points included the frequency Outcome Measures in Rheumatology-OA Research Society International (OMERACT-OARSI)-defined response at 4, 8, 12, and 16 weeks after randomization. FINDINGS The allocated treatment was received by 109 and 106 patients in the GCSB-5 and placebo groups, respectively. At 4 weeks, the median (interquartile range) change in AUSCAN pain score relative to baseline was significantly greater in the GCSB-5 group than in the placebo group (-9.0 [-23.8 to -0.4] vs -2.2 [-16.7 to 6.0]; P = 0.014), with sustained improvement at 8, 12, and 16 weeks (P = 0.039). The GCSB-5 group also had a significantly greater OMERACT-OARSI-defined response rate than did the placebo group at 4 weeks (44.0% vs 30.2%), 8 weeks (51.4% vs 35.9%), 12 weeks (56.9% vs 40.6%), and 16 weeks (50.5% vs 37.7%) (P = 0.0074). The 2 treatments exhibited comparable safety profiles. IMPLICATIONS GCSB-5 was associated with improved symptoms of hand OA, with good tolerability, in these patients. GCSB-5 may be a well-tolerated alternative of, or addition to, the treatment of hand OA. ClinicalTrials.gov identifier: NCT01910116.


Annals of the Rheumatic Diseases | 2014

OP0094 Survival Benefit of Early Use of Cyclosporine in Dermatomyositis-Associated Interstitial Lung Disease

D.J. Go; E.H. Kang; Jin Kyun Park; H.M. Kwon; Yun Jong Lee; Kichul Shin; E.Y. Lee; Y.W. Song; E.B. Lee

Background Interstitial lung disease (ILD) is the most common cause of mortality in patients with dermatomyositis (DM). Cyclosporine has been reported to improve clinical outcome in some patients with DM-associated ILD. Objectives To investigate the benefit of early introduction of cyclosporine on the survival of patients with DM-associated ILD. Methods All the patients with DM-associated ILD, who were treated with cyclosporine at Seoul National University Hospital (SNUH) and Seoul National University Bundang Hospital (SNUBH) between 1990 and 2013, were enrolled. Enrolled patients were diagnosed with DM according to Bohan-Peters classification criteria (n=28) or with clinically amyopathic dermatomyositis (CADM) according to Sontheimers classification criteria (n=19). ILD was diagnosed based on the typical findings on computed tomography (CT) and relevant respiratory symptoms or signs. Kaplan-Meier survival analysis was applied to compare overall mortality rates between patients who took cyclosporine as the initial treatment and those as the delayed treatment. Cox regression analysis was used to estimate the benefit of early treatment with cyclosporine after adjusting confounding characteristics. Results Among the 47 patients who were diagnosed with DM-associated ILD, 16 patients (34.04%) received cyclosprorine initially after diagnosis and 31 patients (65.96%) received cyclosporine after the trial of other immunosuppressants such as corticosteroids, cyclophosphamide or azathioprine. The mean time of follow-up was 43.57 person-years in initial treatment group and 76.23 person-years in delayed treatment group. The mortality rate was significantly lower in the initial treatment group than the delayed treatment group (0.02 person-years vs 0.18 person-years, p=0.0092 by log-rank test). The two groups did not differ in regard to age, sex, duration of disease, presence of autoantibodies, degree of dyspnea at initial visit, initial requirement of oxygen supplement, functional vital capacity (FVC) and diffusion capacity (DLCO) on pulmonary function test (PFT) and the presence of malignancy. Only the proportion of patients with CADM was higher in the initial treatment group than in the delayed treatment group (62.53% vs 29.03%, p=0.027). Survival benefit in the initial cyclosporine treatment remained significant even after adjusting for the CADM status (HR 0.075, 95% CI 0.009 - 0.603, p=0.015 by Cox-regression analysis). Figure 1. Survival curve in initial and delayed use of cyclosporin in patients with dermatomyositis-associated interstitial lung disease. Conclusions This study showed significant survival benefit of initial cyclosporine treatment in patients with DM-associated ILD. A randomized controlled study is warranted to clearly demonstrate the therapeutic benefit of early use of cyclosporine in this potentially fatal disease. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3718


Annals of the Rheumatic Diseases | 2014

AB0622 Clinical Characteristics of Systemic Sclerosis Patients with Interstitial Lung Disease Who do not Require Immunosuppressive Treatment

H.M. Kwon; E.H. Kang; Joung-Hu Park; D.J. Go; Eunshin Lee; Y.W. Song; Hyo-Suk Lee; E.B. Lee

Background Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and internal organs. Although interstitial lung disease (ILD) is a major cause of death in this disease, pulmonary function remains stable in a subset of SSc patients with ILD without any treatment. However, clinical characteristics in this subset of patients are not well characterized. Objectives To investigate clinical characteristics of SSc patients with ILD who do not require additional immunosuppressive treatment for ILD. Methods A total of 151 SSc patients with ILD who received medical care at Seoul National University Hospital between 1978 and 2013 were enrolled in this study. ILD was diagnosed based on chest computed tomography (CT) and the extent of ILD was semi-quantitatively graded into 1-4 (grade 1, <25%; grade 2, 25–50%; grade 3, 50–75%; grade 4, >75% of lung involvement). Detailed baseline clinical characteristics were obtained from medical record review. Mortality was ascertained from medical record review and data from the Statistics Korea. After confirming survival benefit of untreated group versus treated group with Kaplan Meier analysis, clinical characteristics of untreated group were defined by comparison with treated group (chi-square test or Student t-test). Sensitivity test was performed by proving survival benefit of patients with the defined characteristics in the untreated group (log-rank test). Results The mean (standard deviation) age at diagnosis of 151 patients was 48.7 (12.9) years and 88.7% were women. Eighty (52.9%) patients did not receive immunosuppressive treatment for ILD, while 71 (47.0%) patients required immunosuppressive treatment, which includes cyclophosphamide (n=46), azathioprine (n=8), glucocorticoids (n=14) and others (n=3). Interestingly, median survival of non-treatment group was significantly better than treatment group during the follow-up of 1300.80 person-years (p=0.029 by log-rank test). Compared with treatment group, non-treatment group had higher baseline predicted % of forced vital capacity (FVC, 79.2±16.8% vs. 68.0±18.2, p<0.001), predicted % of diffusion capacity of carbon monoxide (DLCO, 66.4±20.5 vs. 52.0±17.9, p<0.001), lower CT grade (Grade 1: 89.6% vs. 54.7%, p<0.001), absence of pulmonary arterial hypertension (83.8% vs. 64.8%, p=0.013) and absence of gastrointestinal involvement (60.0% vs. 39.0%). Other baseline characteristics were not different, which include age at diagnosis, duration of disease, skin subset, profile of autoantibodies, involvement of heart or kidney and subtypes of ILD on CT. Among the non-treatment group, patients with the defined characteristics showed significant survival benefit than those without the characteristics (p=0.0047 by log-rank test). Conclusions Watch and wait approach may be applied to patients with SSc-associated ILD with minimal pulmonary infiltrates on CT scan and absence of pulmonary arterial hypertension at ILD diagnosis. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3686


Annals of the Rheumatic Diseases | 2016

OP0059 Serum CXCL10 Levels Are Associated with Clinical Manifestations and Disease Activity in Behcet's Disease

Sung Joong Lee; E.H. Kang; Bo-Youl Choi; Sangwoo Kang; S.H. Shon; Joong Shin Park; Joung-Hu Park; E.Y. Lee; E.B. Lee; Y.W. Song

Background Chemokines are multifunctional mediators that control leukocyte recruitment into the inflammatory sites and enhance immune responses. It remains to be investigated which chemokines are important in Behcets disease (BD). Objectives The objective of this study was to investigate serum levels of (C-X-C motif) CXC chemokines in BD patients and its association with clinical manifestations and disease activity. Methods Blood samples were collected from 109 BD patients and 34 age-, sex matched healthy controls (HCs). Twenty two follow-up samples were collected in BD patients. Serum CXC chemokines were assayed for the neutrophil chemoattractants (CXCL1 and CXCL8) and lymphocyte chemoattractants (CXCL9, CXCL10, CXCL12, CXCL13 and CXCL16) by using a multiplex assay. Cell surface makers such as CD3, CD4 and CXCR3 in peripheral blood mononuclear cells were investigated by flow cytometry. The clinical features including disease activity, laboratory tests and current medication were evaluated at the time of blood collection. C-X-C chemokine receptor 3 (CXCR3) expression in skin and intestinal lesions from BD patients were assessed via immunohistochemistry. Results Serum levels of CXCL8, CXCL10 and CXCL12 were significantly higher in the BD patients than in HC (p=0.001, p=0.007 and p=0.003, respectively). Serum CXCL10 levels were significantly correlated with disease activity in both Behcets Disease Current Activity Form (BDCAF) and Behcets Syndrome Activity Score (BSAS) (rho =0.336, p<0.001 and rho =0.253, p=0.009, respectively) as well as with number of genital ulcer and erythema nodosum (EN) (rho =0.222, p=0.020 and rho =0.329, p<0.001, respectively). In follow-up BD patients, changes of serum CXCL10 levels were correlated with those of BDCAF (rho =0.425, p=0.048). CXCR3 receptor expression was significantly increased on CD3 positive T cells versus CD3 negative cells in peripheral blood mononuclear cells of both BD patients and HCs (p=0.009 and p=0.031, respectively). Levels of serum CXCL10 were inversely correlated with percentage of CXCR3 expression on CD3 positive T cells in BD patients (rho = -0.523, p=0.022). In immunohistochemistry, the CXCR3 positive inflammatory cells were increased in skin lesions of BD patients than in those of HCs. Conclusions These results suggest that CXCL10/CXCR3 axis contribute to pathogenesis of BD particularly mucocutaneous lesions. Measurement of serum CXCL10 may help to assess disease activity in BD patients. Disclosure of Interest None declared


Annals of the Rheumatic Diseases | 2015

AB0928 Clinical Usefulness of Measuring Red Blood Cell Distribution Width in Patients with Gout Attack

Seok Won Chung; Ji Ae Yang; Jin Hak Lee; E.H. Kang; Yun Jong Lee; Y.W. Song; You Jung Ha

Background Red blood cell distribution width (RDW) is a biomarker quantifying the variability of red blood cell size (anisocytosis) in the peripheral blood. High RDW is associated with inflammatory burden and it has been suggested as a potential marker for cardiovascular prognosis, mortality, or reflecting renal function in the various clinical conditions 1. A recent study found the significant association between serum uric acid level and RDW in patients with untreated essential hypertension2. Gouty arthritis is an acute and severe inflammatory arthritis attributable to hyperuricemia, and closely associated with renal dysfunction and cardiovascular diseases. However, few studies have yet investigated the clinical significance of RDW in patients with gout. Objectives The aim of this study was to investigate the potential association of RDW value with clinical features in patients presenting with acute gout attack. Methods The medical records of patients who visited emergency room of Seoul National University Bundang Hospital for acute gout attack, from March 2003 to April 2014, were retrospectively reviewed. Cases were stratified into three groups according to the RDW tertiles (<12.9%, 12.9-13.4% and >13.4%) and clinically relevant differences were evaluated by the ANOVA test or the chi-square test. The Pearsons correlation approach was used to analyze the correlation between two continuous variables. To identify significant determinants influencing RDW, we used multiple linear regression analysis. Results Two-hundred and thirty-six patients with acute gout attack were included. The mean age was 49.38±16.85 years and the male ratio was 92.3% (n=218). The patients in the highest RDW tertile tended to be older, had higher levels of hemoglobin and lower levels of albumin, and had more recurrence of gout attack and renal impairment. RDW showed significant weak positive correlation with age (γ=0.224, p=0.001) and creatinine level (γ=0.237, p<0.001) and negative modest correlation with albumin level (γ= -0.332, p<0.001) in gout attack. However, RDW was not significantly correlated with serum uric acid level and acute phase reactants. In multiple linear regression analysis, increase in RDW was independently associated with recurrence of gout attack (p<0.001) and presence of chronic kidney disease (p=0.009) (Table 1). Conclusions Our data shows that high RDW in acute gout attack is related to the recurrence of gout attack and coexistence of chronic kidney disease. In acute gout attack, RDW, an easy and quick measurable index, may represent renal dysfunction rather than inflammatory burden or uric acid level, and physicians who treat acute gouty arthritis with high RDW should pay attention to the recurrence of gout attack and treatment. References Lippi G, Targher G, Montagnana M, Salvagno GL, Zoppini G, Guidi GC. Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. Arch Pathol Lab Med 2009;133:628-32. Luo M, Li ZZ, Li YY, Chen LZ, Yan SP, Chen P, et al. Relationship between red cell distribution width and serum uric acid in patients with untreated essential hypertension. Sci Rep 2014;4:7291. DOI: 10.1038/srep07291 Disclosure of Interest None declared


Annals of the Rheumatic Diseases | 2015

SAT0451 The HLA Class II Profile in Korean Patients with Inflammatory Myositis

D.J. Ko; E.H. Kang; H.M. Kwon; Jun Won Park; Sung Joong Lee; Seok Won Chung; You Jung Ha; Yun Jong Lee; E.Y. Lee; Y.W. Song

Background Polymyositis (PM) and dermatomyositis (DM) is known to be associated with certain HLA alleles in several ethnic groups including Caucasians, African-Americans, and the Japanese. Objectives To investigate the profile of HLA class II alleles in Korean patients with PM and DM Methods Sequencing based genotyping for HLA-DRB1 and -DPB1 was performed in 140 Korean patients with DM (n=104) or PM (n=36) and in 207 healthy controls. Associations of each HLA-DR or -DP allele with myositis or clinical subsets of myositis were examined. Results HLA-DRB1*14:54 (odds ratio [95% confidence interval] 1.05 [1.01-1.09]), -DRB1*15:02 (2.44 [1.03-5.81]), -DRB1*16:02 (1.04 [1.00-1.07], and -DPB1*09:01 (2.44 [1.03-5.81]) were found to be susceptibility alleles while HLA-DRB1*14:01 (0.93 [0.90-0.97]) and -DRB1*15:01 (0.38 [0.18-0.79]) to be protective alleles for inflammatory myositis (Table 1). In DM, HLA-DRB1*15:02 (3.14 [1.30-7.62]) and -DPB1*09:01 (2.87 [1.17-7.05]) carriers were more frequent while HLA-DRB1*14:01 (0.93 [0.90-0.97]), -DRB1*15:01 (0.30 [0.12-0.74]), and -DPB1*04:02 (0.44 [0.20-0.94]) carriers were less frequent than controls. In PM, HLA-DRB1*14:03 (6.52 [1.78-23.81]), and -DRB1*14:54 (1.13 [1.00-1.23]) carriers were more frequently observed. When PM and DM were compared, HLA-DRB1*14:03 carriers were more frequently observed in PM (5.43 [1.23-24.02]). When the association between each allele and clinical subsets was examined, patients with interstitial lung disease (ILD) carried HLA-DRβ1*04:03 (6.34 [1.35-29.76]), -DRβ1*07:01 (0.22 [0.08-0.64]), -DRβ1*09:01 (0.16 [0.05-0.60]) -DRβ1*12:02 (2.91 [1.16-8.01]) DRβ1*15:01 (0.10 [0.01-0.80]), -DPβ1*14:01 (8.90 [1.08-73.21]), and -DPβ1*17:01 (0.11 [0.01-0.92]) more frequently than patients without. DM patients with ILD showed higher frequency of HLA-DRβ1*04:05 than DM patients without ILD (4.68 [1.24-17.74]). Other associations included dysphagia with HLA-DRβ1*08:02 (6.73 [1.51-30.00]), -DRβ1*14:54 (5.19 [1.09-24.57]), and -DPβ1*03:01 (5.19 [1.09-24.57]), arthralgia with HLA-DRβ1*03:01 (4.79 [1.21-18.98]) and -DPβ1*02:01 (2.30 [1.10-4.82]), and mechanics hand with HLA-DRB1*08:03 (3.25 [1.12-9.45]) and -DRB1*12:02 (5.04 [1.66-15.29]). Regarding skin rashes, heliotrope rash was associated with HLA-DRβ1*09:01 (2.98 [1.05-8.46]) and -DPβ1*05:01 (0.41 [0.18-0.87]), Gottrons papules with HLA-DRβ1*14:05 (8.77 [1.07-72.17]), -DPβ1*02:01 (2.29 [1.11-4.73]), -DPB1*02:02 (0.086 [0.01-0.67]), and -DPB1*05:01 (0.41 [0.20-0.85]), and shawl sign with HLA-DRB1*14:05 (4.67 [1.15-18.99]) and -DPB1*14:01 (4.67 [1.15-18.99]). Cancer development was associated with HLA-DRB1*12:01 (7.25 [1.65-31.89]) and -DRB1*13:02 (0.81 [0.74-0.88]). No HLA-DRB1 or -DPB1 allele was found to be associated with anti-Jo1 antibody. Conclusions Korean patients with inflammatory myositis showed a unique profile of HLA-DR and -DP alleles compared with other ethnic groups. Alleles associated with disease susceptibility were different between PM and DM. Clinical subsets, particularly ILD, showed different immunogenetic backgrounds. Disclosure of Interest None declared


Annals of the Rheumatic Diseases | 2015

SAT0475 Cancer Risks in Korean Patients with Myositis: Comparison Between Cancers Related and Unrelated to Myositis Activity

S.J. Lee; E.H. Kang; Seok Won Chung; You Jung Ha; Yun Jong Lee; E.Y. Lee; Y.W. Song

Background High risk of cancers in patients with myositis is partly explained by common expression of myositis-associated autoantigens in cancer tissues and in regenerating muscles. Malignancies found in myositis patients would be either cancers directly involved in myositis development or cancers that are not different from those found in general population. Objectives To compare the standardized incidence ratio (SIR) of cancers related and unrelated to myositis activity in Korean patients with myositis Methods Medical records of 283 patients with polymyositis (PM) or dermatomyositis (DM) were reviewed to identify 52 cancer cases. SIR was calculated using cancer incidence of period-, age- and sex-matched Korean population. Under the hypothesis that cancer tissues should temporally overlap with active myositis in patients whose cancers are involved in myositis development, cancer cases were divided according to the presence (group A, cancers related to myositis activity, n=32) or absence (group B, cancers unrelated to myositis activity, n=20) of either newly diagnosed, remnant, or recurred cancers at any time during active phase of myositis. SIRs of groups A and B were compared. Results The mean (±standard deviation) age at myositis diagnosis was 47.7±15.1 years in all patients and 77.7% were female. The overall SIR was 3.0 [2.2-4.0] (4.4 [2.6-6.8] in men; 2.51 [1.7-3.6] in women). Although a majority of cancers were found from 50s to 70s, the highest SIR, 22.8 [4.7-66.5], was observed in 20s. When stratified by intervals between myositis and cancer diagnoses, no elevated SIR was noted except for 10.3 [6.8-15.1] within 1 year of myositis diagnosis, and for 3.2 [1.2-6.9] during the next 2 years. The most frequent cancer was non-Hodgkins lymphoma (NHL, 23.0 [9.3-47.4]). SIRs of esophageal cancer (23.6 [4.9-68.8]), multiple myeloma (MM, 22.9 [2.8-82.7]), lung cancer (6.4 [2.9-12.1]), and adenocarcinoma of unknown primary (ACUP, 25.7 [7.0-65.7]) were also higher than general population. When compared groups A and B, group A tended to be more male-predominant (14/30 vs 5/22, p=0.077) and had an older age at myositis diagnosis than group B (60.5±11.1 vs 49.3±16.6 years, p=0.022). There was no difference in PM and DM distribution. The SIR in group A was 1.8 [1.2-2.6] (3.0 [1.6-5.1] in men; 1.3 [0.8-2.2] in women) while in group B, it was 1.2 [0.8-1.9] (1.4 [0.5-3.0] in men; 1.2 [0.6-2.0] in women). Elevated SIRs were observed in 60s in group A (2.6 [1.4-4.5]) and in 20s in group B (22.8 [4.7-66.5]). The SIR within 1 year of myositis diagnosis was 9.9 [6.4-14.7] in group A while in group B, there was no temporal relationship between myositis and cancer. Elevated SIRs were observed for esophageal cancer (23.6 [4.9-68.8]), NHL (16.4 [5.3-38.3]), and ACUP (25.6 [7.0-65.7]) in group A while lung cancer (3.6 [1.2-8.3]) in group B. Conclusions Cancer risk in Korean patients with myositis was approximately 3 times higher than general population. SIRs of NHL (23.0 [9.3-47.4]), esophageal cancer (23.6 [4.9-68.8]), MM (22.9 [2.8-82.7]), lung cancer (6.4 [2.9-12.1]), and ACUP (25.7 [7.0-65.7]) were significantly higher than general population. Two distinctive groups of cancers were noted according to the relationship with myositis activity in terms of incidence, temporal relationship with myositis, age distribution, and histologic types of cancers. Disclosure of Interest None declared


Annals of the Rheumatic Diseases | 2015

THU0297 Serum CXCL8, 10 and 12 are Increased in Patients with Behcet's Disease and CXCL10 Levels are Correlated with Number of Erythematous Nodosum

Sung Joong Lee; Jun-Hyeok Choi; Bo-Youl Choi; D.J. Ko; H.M. Kwon; Jinyoung Moon; E.H. Kang; Jin Kyun Park; E.Y. Lee; E.B. Lee; Y.W. Song

Background Chemokines are multifunctional mediators that control leukocyte recruitment into the inflammatory sites and enhance immune responses. It remains to be investigated which chemokines are important in Behcets disease (BD). Objectives The objective of this study was to investigate serum levels of neutrophil and lymphocyte chemoattractants in BD patients and its association with disease activity and symptoms. Methods We collected sera from patients with BD (n=64) and age-, sex matched healthy controls (n=21). Serum levels of chemokines were assayed for the neutrophil chemoattractants (CXCL1 and CXCL8) and lymphocyte chemoattractants (CXCL9, CXCL10, CXCL12, CXCL13 and CXCL16) by using a multiplex assay. Behcets disease current activity form (BDCAF) and symptoms were evaluated at the time of blood collection. Results Serum levels of CXCL8, CXCL10 and CXCL12 were significantly higher in the BD patients than in healthy controls (p<0.001, p=0.050 and p=0.002, respectively). Serum chemokine levels were not associated with BDCAF in BD patients. But CXCL10 levels were significantly higher in patients with erythematous nodosum (EN) than in patients without EN (p=0.008). AdditionaIly, CXCL10 levels were significantly correlated with number of EN (r=0.338, p=0.006). There was no difference of serum level of CXCL1, CXCL9, CXCL13 and CXCL16 between BD and healthy controls Conclusions Serum levels of CXCL8, CXCL10 and CXCL12 were significantly higher in the BD patients than in healthy controls. CXCL10 levels were correlated with number of EN in BD patients. Disclosure of Interest None declared


Annals of the Rheumatic Diseases | 2014

AB0004 Erap1 Polymorphisms in Korean Patients with Behcet's Disease

E.H. Kang; Sung Joo Kim; Changwon Kang; Young Mo Kang; Suk-Hwan Kang; H.J. Baek; Eun-Jung Lee; Yun Jong Lee; E.B. Lee; Y.W. Song

Background Non-synonymous ERAP1 single nucleotide polymorphisms (SNPs), rs10050860 and rs17482078, were found to be associated with Behcets disease (BD) by a recessive model in Turkish patients [1]. Objectives To investigate the association between ERAP1 SNPs and BD in Korean patients. Methods DNA samples were obtained from 391 patients who met the International Study Group criteria for BD and from 800 age- and sex-matched healthy controls. Nineteen tag-SNPs (rs27980, rs27582, rs27038, rs149481, rs149173, rs27039, rs27043, rs42398, rs10050860, rs151928, rs13170045, rs27710, rs27529, rs25866, rs26652, rs26498, rs27045, rs10062964, rs28050) in and within 1kb from ERAP1 were selected for genotyping. Results Allele-based analysis failed to detect any significant associations between 19 SNPs and BD after correction for multiple testing. In genotype-based analysis, only an intronic variant rs27043 was associated with BD by a dominant model (for AG+GG genotypes, 85.8% in patients vs. 72.4% in controls; OR [95% CI] =2.29 [1.65-3.20], p=6.2x10–7, corrected p=1.18x10-5). This association was significant in patients with uveitis (84.4% vs. 72.4%; OR [95% CI] =2.06 [1.28-3.29], p=0.002, corrected p=0.038) as well as in patients without uveitis (85.4% vs. 72.4%, OR [95% CI] =2.23 [1.46-3.41], p=0.0001, corrected p=0.0019) compared to controls. The non-synonymous rs10050860 found to be associated with BD in a Turkish GWAS did not show any statistical significance (minor allele frequencies of 4.7% in patients and 4.9% in controls). Conclusions An intronic variant rs27043 was associated with BD notably by a dominant model in a Korean population. Efforts to impute genotypes using a reference panel from Korean/Asian HapMap data are underway to fully examine non-synonymous SNPs in strong linkage disequilibrium with rs27043 and their haplotype effects. References Kirino Y, Bertsias G, Ishigatsubo Y, et al. Genome-wide association analysis identifies new susceptibility loci for Behçets disease and epistasis between HLA-B*51 and ERAP1. Nat Genet 2013; 45: 202-7. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3438

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Y.W. Song

Seoul National University

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Yun Jong Lee

Seoul National University Bundang Hospital

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E.B. Lee

Seoul National University Hospital

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E.Y. Lee

Seoul National University Hospital

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You Jung Ha

Seoul National University Bundang Hospital

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H.M. Kwon

Seoul National University Hospital

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Jin Kyun Park

Seoul National University

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Kichul Shin

Seoul Metropolitan Government

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D.J. Go

Seoul National University Hospital

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