Y.B. Joo

Preparation of an imogolite/poly(acrylic acid) hybrid gel

Many efforts in the field of hydrogels have been focused toward increasing the mechanical strength of the gel using inorganic materials. In this study, we synthesized a hydrogel that has excellent mechanical properties using surface-modified inorganic nanofibers composed of imogolite (Al2SiO3(OH)4), which is a hydrated aluminum silicate that has a hollow tube structure. Gamma ray radiation generates peroxide radicals on the nanofibers (imogolite), resulting in an additive free hybrid hydrogel. Structural optimization was carried out by changing the composition of imogolite and poly(acrylic acid). Chemical bonding between the nanofiber and the polymer was simulated by a cluster model and characterized by wide area Raman spectroscopy. The results indicate that imogolite embedded in a polymer matrix can align along the direction of an elongational force, as confirmed by small angle X-ray scattering (SAXS).

Late-onset systemic lupus erythematosus: Is it “mild lupus”?

Objective The objective of this paper is to investigate the clinical characteristics and prognosis of patients with late-onset systemic lupus erythematosus (SLE) using a prospective observational cohort. Methods Late-onset SLE (≥50 years old) was compared with adult-onset SLE (≥18 and <50 years old) using 1997 ACR classification criteria for SLE, autoantibodies, disease activity measured by Adjusted Mean SLE Disease Activity Index (AMS), and damage measured by Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI). The standardized mortality ratio (SMR) was calculated. Results A total of 917 patients with SLE were enrolled. The mean number of cumulative ACR criteria in late-onset SLE (nu2009=u200932, 3.5%) was lower than that in adult-onset SLE (4.6u2009±u20091.2 vs. 5.5u2009±u20091.4, pu2009<u20090.05). The percentage of patients with low complement was lower in late-onset SLE than adult-onset SLE (pu2009<u20090.05). AMS was also lower in late-onset SLE (2.7u2009±u20092.1 vs. 4.3u2009±u20092.6, pu2009<u20090.01), but SDI was similar between the two groups (50% vs. 43.4%, pu2009=u20090.58). The SMR of late-onset SLE was 1.58 (95% CI 0.58–3.43), while the SMR of adult-onset SLE was 3.34 (2.34–4.63). Conclusion Compared with adult-onset SLE, late-onset SLE has a lower number of ACR criteria and lower disease activity. Organ damage is not different, but prognosis and mortality are more favorable.

Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, nu2009=u2009132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20u2009g (odds ratio (OR) 3.62, pu2009=u20090.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, pu2009<u20090.001) remained as significant risk factors for AVN. Patients with cumulative corticosteroid doseu2009>u200920u2009g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors (pu2009<u20090.001). RERI, AP and S, which define the strength of interactions between two risk factors, were 9.01 (95% confidence interval (CI) 1.30–16.73), 0.58 (95% CI 0.36–0.81) and 2.66 (95% CI 1.42–4.99), respectively, supporting the presence of synergistic interactions in the development of symptomatic AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE, especially in patients with high-dose corticosteroid and immunosuppressant use regardless of clinical manifestations and disease activity.

THU0356 Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus

Background Avascular necrosis (AVN) is one of the most common organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. Objectives The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyse their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, in whom damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory, and therapeutic variables were analysed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1,219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n=132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20u2009g (odds ratio (OR) 3.08, p=0.005) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.34, p=0.002) remained as significant risk factors for AVN. Patients with cumulative corticosteroid dose >20u2009g and immunosuppressants use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors (p<0.001). RERI, AP, and S, which define the strength of interactions between two risk factors, were 9.01 (95% confidence interval (CI) 1.30–16.73), 0.58 (95% CI 0.36–0.81), and 2.66 (95% CI 1.42–4.99), respectively, supporting the presence of synergistic interactions in the development of symptomatic AVN in our Korean lupus cohort.Abstract THU0356 – Table 1 Synergistic effect of total cumulative steroid dose and use of immunosuppressants in development of AVN in SLE patients No. patients with AVN No. patients without AVN ORa (95%u2009CI) p-value Total cumulative steroid dose≤20u2009g and immunosuppressants (-) 11 314 1.00 Total cumulative steroid dose>20u2009g and immunosuppressants (-) 17 168 3.08 (1.40–6.81) 0.005 Total cumulative steroid dose≤20u2009g and immunosuppressants (+) 18 121 4.34 (1.99–9.49) <0.001 Total cumulative steroid dose>20u2009g and immunosuppressants (+) 64 134 15.44 (7.64–31.19) <0.001 RERI 9.01 (1.30–16.73) AP 0.58 (0.36–0.81) S 2.66 (1.42–4.99) AVN: avascular necrosis; SLE: systemic lupus erythematosus; OR: odds ratio; CI: confidence interval; RERI: relative excess risk due to interaction; AP: attributable proportion; S: synergy index a. Odds ratios were adjusted for sex, age and disease duration. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE, especially in patients with high-dose corticosteroid and immunosuppressant use regardless of clinical manifestations and disease activity. Disclosure of Interest None declared

AB0713 Spectrum of Atlantoaxial Ankylosis (AAA) in The Ankylosing Spondylitis (AS): Is It Really Chronological Changes That Occur with Disease Progression or Are There Two Completely Different Pathways?

Background The morphologic characteristics of atlantoaxial ankylosis in AS patient and suggests different pathways of involvement resulting in atlantoaxial subluxation in AS patients Objectives To evaluate morphologic characteristics of AAA in AS patient and classify them into categories which reflects the end-stage manifestations of two differents disease pathways. Methods Plain radiographs of cervical spine in 62 AS patients with AAA were reviewed. We classified AAA in AS patients into three subtypes: loss of atlantodental interval (type I), ankylosis of facet joint (type II) and ankylosis of anterior longitudinal ligament or anterior atlantooccipital membrane with cervical spine (type III). And then, we categorized 62 AS patients with AAA into two subgroups: group A (21 patients) with only synovial joint involvement of AS (type I or type II or both) and group B (41 patients) with enthesis involvement of AS with additional synovial joint involvement (type III plus type I or type II or both). We compared the results of mSASSS and disease duration between group A and B. Results The mean cervical mSASSS of patients in group A and B were 27.3 and 16.0 each (p value, 0.196). The mean duration of AS patients in group A and B were 23.7 and 23.6 years each. There was no siginificant differences in cervical, lumbar and total mSASSS or disease duration between the two groups. Conclusions We propose that atlantoaxial joint involvement in the AS patients is not chronological changes that occur with disease progression, but rather it is end-stage manifestation of two different pathways: one only involving synovial joint and the other one involving both synovial joint and enthesis. References Martel W. The occipito-atlanto-axial joints in rheumatoid arthritis and ankylosing spondylitis. Am J Roentgenol Radium Ther Nucl Med 1961;86:223–240 Meijers KA, van Voss SF, Francois RJ. Radiological changes in the cervical spine in ankylosing spondylitis. Ann Rheum Dis1968;27:333–338 Lee HS, Kim TH, Yun HR, Park YW, Jung SS, Bae SC, et al. Radiologic changes of cervical spine in ankylosing spondylitis.Clin Rheumatol 2001;20:262–266 Laiho K, Kauppi M. The cervical spine in patients with ankylosing spondylitis. Clin Exp Rheumatol 2002;20:738 Disclosure of Interest None declared

SAT0329 Lupus Nephritis Is Associated with More Corticosteroid-Associated Organ Damage but Less Corticosteroid Non-Associated Organ Damage

Background Lupus nephritis (LN), one of the most serious manifestations of systemic lupus erythematosus (SLE), has been suggested to be a predictor of organ damage accrual. Also, LN is considered a strong determinant for survival. Since patients with LN are more exposed to immunosuppressive agents, such as cyclophosphamide and high-dose corticosteroid, and also have high inflammatory burdens, they might be more vulnerable to organ damage than patients without LN. Thus, proper adjustment for these potentially confounding variables needs to be performed to determine the precise effect of LN on organ damage. Also, it is important to identify the types of organ damage that are associated with LN. However, these aspects have not been previously investigated. Objectives We investigated the impact of LN on organ damage accrual and mortality after adjusting for potential confounders. In particular, we identified the types of organ damage that are more or less associated with LN. Methods Patients with SLE were propectively enrolled and followed from 198 to 2012 in the Hanyang BAE Lupus cohort. LN was defined as the disorder with the persistent proteinuria greater than 0.5 grams per day Organ damage was assessed using SLICC/ACR Damage Index (SDI). Damage presumed to be corticosteroid associated (cataract, avascular necrosis, diabetes and osteoporosis items) and non-associated (5 pulmonary, 5 gastrointestinal, erosive arthritis, 3 skin, premature gonadal failure and malignancy items) selected from 41 items were compared. Association of LN with organ damage was analyzed using multivariable logistic regression analysis, adjusting for potential confounders. Age- and sex adjusted standardized mortality ratio (SMR) was evaluated in patients with or without LN. Results Among the 1,112 SLE patients, 515 (46.3%) had LN. Patients with LN showed higher percentage of male (p=0.003), were younger at diagnosis (p<0.001), had longer disease duration (p<0.001), higher adjusted mean SLE Disease Activity Index (AMS) score (p<0.001), lower percentage of prescribed anti-malarial agents (p<0.001), and higher percentage of corticosteroids (p<0.001) and immunosuppressant use. After mean follow-up of 7.6 years, patients with LN had higher percentage of overall organ damage than patients without LN (51.5% vs 35.7%, p<0.001) with OR of 1.40, after adjusting for age at diagnosis, gender, disease duration, anti-malarial agents, corticosteroids and immunosuppressant. However, LN was not associated with non-renal organ damage (p=0.883). In subgroup analysis, the odds of corticosteroid-associated damage was higher in patients with LN (2.06, 95% CI 1.43–2.96), but whereas odds of non-associated damage was lower in patients with LN (0.50, 95% CI 0.35–0.75), compared not having LN. Age- and sex adjusted SMR of patients with LN was 5.17 (95% CI 3.49–7.38) and 2.32 (95% CI 1.47–3.48) in patients without LN. Conclusions LN was associated with more overall organ damage but not more non-renal organ damage. Patients with LN had more corticosteroid-associated damage, but less corticosteroid non-associated damage compared with patients without LN. Additionally, the SMR of patients with LN was significantly higher than the SMR of patients without LN Disclosure of Interest None declared

AB0712 Analysis of Different Manifestations in The Cervical Spine Involvement of Longstanding Ankylosing Spondylitis: Atlantoaxial Ankylosis (AAA) and Atlantoaxial Subluxation (AAS)

Background Atlantoaxial ankylosis (AAA) is another late manifestation of cervical spine involvement in longstanding AS and suggest that higher cervical mSASSS is more related with the development of AAA than atlantoaxial subluxation (AAS). AAA does not cause as much cervical instability as AAS. Objectives To analyze radiologic and clinical findings of atlantoaxial ankylosis and atlantoaxial subluxation in ankylosing spondylitis Methods A total of 150 AS patients (145 men, 5 women, mean age, 36.8 years) who had AAA (60 men and 2 women, mean age, 60 years) or AAS (85 men and 3 women, mean age, 34 years) were randomly gathered and underwent at least two plain radiographs of lateral cervical spine on flexion. The atlantodental interval more than 3mm was considered as AAS. Loss of atlantodental interval was considered as AAA. The plain radiographs of lateral cervical spine were independently analyzed by two radiologists. Interobserver reliability between reader 1 and 2 in scoring mSASSS in AS was analyzed. We compared the results of mSASSS between AAS and AAA to see if it was related to severity or duration of the disease. Results The mean mSASSS of AS patients with AAA and AAS were 40.1 and 16.5 respectively and the mean duration of AS patients with AAA and AAS were 19.3 and 13.7 years each. There was a significantly (p<0.05) higher total mSASSS, especially cervical spine mSASSS, for AS patients with AAA than those with AAS after mSASSS was corrected for age and duration. But, disease duration was not significantly related with the development of AAA compared with that of AAS. Conclusions We found that it has incidence as high as AAS and both are similar in that they are late presentation of AS and occur in patient with long duration. We found that AAA is another manifestation of cervical spine involvement in longstanding AS and is related to severity of the AS reflected by higher cervical mSASSS. References Martel W. The occipito-atlanto-axial joints in rheumatoid arthritis and ankylosing spondylitis. Am J Roentgenol Radium Ther Nucl Med 1961;86:223–240 Meijers KA, van Voss SF, Francois RJ. Radiological changes in the cervical spine in ankylosing spondylitis. Ann Rheum Dis 1968;27:333–338 Lee HS, Kim TH, Yun HR, Park YW, Jung SS, Bae SC, et al. Radiologic changes of cervical spine in ankylosing spondylitis. Clin Rheumatol 2001;20:262–266 Laiho K, Kauppi M. The cervical spine in patients with ankylosing spondylitis. Clin Exp Rheumatol 2002;20:738 n> Disclosure of Interest None declared

THU0003 Searching for the Genetic Variants Associated with Bone Erosion of Rheumatoid Arthritis Using High-Density Genotype Data for Immune Loci in a Korean Population

Background Radiographic joint damage is highly variable among rheumatoid arthritis patients. Since the heritability of joint destruction rate was estimated to 45-58% in previous twin and the Icelandic RA-population studies, it is highly suggested that genetic variants are involved in the process of joint destruction and cause the different amount of joint damage among the patients. Objectives We aimed to examine genetic variants and biological pathways associated with bone erosion using high-density genotype data for immune loci in Koreans. Methods We analyzed ∼100,000 immune-loci SNPs for their associations with bone erosion in 1,142 RA patients. The subjects were genotyped by Immunochip, a high-density genotyping array for immune disease loci (n=343), or imputed for the Immunochip SNPs from our previous genomoe-wide association study (GWAS) array by SHAPEIT and IMPUTE2 (n=799). The patients were classified into two groups based on the Steinbrocker staging system: non-erosive (stages I and II) and erosive (stages III and IV) RA. The association between SNPs and bone erosion was tested for the genotyping and imputation-based data separately, by multivariate logistic regression with adjustment of age, sex, disease duration, and smoking status at symptom onset using PLINK. The association results from both datasets were combined in a fixed-effect meta-analysis by using GWAMA. Enrichment of associated variants in the known biological pathways and gene-sets was further tested from the meta-analysis results by MAGENTA. Results By testing the associations between the 99,177 SNPs and bone erosion in 446 erosive and 387 non-erosive RA patients, rs10782763 (OR=1.64, P=2.95×10-5) and rs12095896 (OR =1.60, P=5.28×10-5) near LPHN2 and rs10263303 (OR=1.81, P=8.41×10-5) near PTPRN2 (or DNAJB6) were potential SNPs associated with bone erosion in RA, but none reached the genome-wide significance threshold. In the gene-set enrichment analysis, five candidate causal pathways were identified: the ataxia telangiectasia-mutated gene (ATM), vascular endothelial growth factor (VEGF), C-C chemokine receptor type 5 (CCR5), Src by protein-tyrosine phosphatase alpha (srcRPTP), and free radical induced apoptosis (FREE) pathways (P<0.05, BioCarta database).Table 1. Polymorphism possibly associated with bone erosion in patients with RA Meta-analysis iCHIP data Imputed iCHIP data SNP CR Gene name Ref. allele Risk allele OR P value OR P value OR P value rs10782763 1 LPHN2 C A 1.68 2.95x10-5 1.80 1.63x10-2 1.64 5.85x10-4 Rs12095896 1 LPHN2 C A 1.64 5.28x10-5 1.76 2.05x10-2 1.60 8.59x10-4 Rs10263303 7 DNAJB6, PTPRN2 G A 1.80 8.41x10-5 1.77 8.04x10-2 1.81 4.19x10-4 Conclusions We could not find any immune-loci SNPs surpassing genome-wide significance level in our study subjects, although we identified suggestive associations at several SNPs, raising the possibilities that genetic variants for joint erosion would locate beyond the immune loci, unlike RA susceptibility genes and there is highly heterogenous genetic etiology in joint erosion. In addition, we identified five biological pathways associated with bone erosion, which might provide insight into the molecular mechanisms underlying the radiographic damage in RA. Disclosure of Interest None declared