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ObjectiveGenome-wide association studies (GWAS) have identified >100 risk loci for systemic lupus erythematosus (SLE), but the disease genes at most loci remain unclear, hampering translation of these genetic discoveries. We aimed to prioritise genes underlying the 110 SLE loci that were identified in the latest East Asian GWAS meta-analysis.MethodsWe built gene expression predictive models in blood B cells, CD4+and CD8+T cells, monocytes, natural killer cells and peripheral blood cells of 105 Japanese individuals. We performed a transcriptome-wide association study (TWAS) using data from the latest genome-wide association meta-analysis of 208 370 East Asians and searched for candidate genes using TWAS and three data-driven computational approaches.ResultsTWAS identified 171 genes for SLE (p–5); 114 (66.7%) showed significance only in a single cell type; 127 (74.3%) were in SLE GWAS loci. TWAS identified a strong association betweenCD83and SLE (p–8). Meta-analysis of genetic associations in the existing 208 370 East Asian and additional 1498 cases and 3330 controls found a novel single-variant association at rs72836542 (OR=1.11, p=4.5×10–9) aroundCD83. For the 110 SLE loci, we identified 276 gene candidates, including 104 genes at recently-identified SLE novel loci. We demonstrated in vitro that putative causal variant rs61759532 exhibited an allele-specific regulatory effect onACAP1, and that presence of the SLE risk allele decreasedACAP1expression.ConclusionsCell-level TWAS in six types of immune cells complemented SLE gene discovery and guided the identification of novel genetic associations. The gene findings shed biological insights into SLE genetic associations.

ObjectiveSystemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations.MethodsWe newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations.ResultsWe identified 113 genetic regions including 46 novel loci at genome-wide significance (p−8). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (rg=−0.242) and non-albumin protein (rg=0.238).ConclusionThis study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.

Hyperuricemia plays an essential role in the development of gout. Despite the clinical importance of hyperuricemia, a direct relationship between oral health and hyperuricemia has not been established. Therefore, we aim to investigate the association between oral health and hyperuricemia in Korean adults.We selected 17,584 subjects from the Korea National Health and Nutrition Examination Survey 2016–2019 database. Oral health-related variables included the number of dental caries, regular tooth brushing, use of secondary oral products, and regular dental examination. The odds ratio (OR) and 95% confidence intervals (CIs) for hyperuricemia were calculated using a multivariable-adjusted logistic regression model.In all subjects, oral health status with dental caries and oral health behaviors, including tooth brushing; secondary oral products; and regular dental examination, were significantly associated with hyperuricemia. The adjusted OR and 95% CIs for hyperuricemia comparing more than three dental caries with no dental caries were 1.28 (1.08–1.51). The adjusted OR and 95% CIs for hyperuricemia in regular tooth brushing, use of secondary oral products, and regular dental examination were 0.78 (0.67–0.91), 0.91 (0.82–1.00), and 0.86 (0.78–0.95), respectively. Notably, the association between oral health and hyperuricemia was more prominent in male subjects. In addition, when subjects were grouped by the scoring system regarding oral health, the prevalence of hyperuricemia was lower in groups with a better oral health score.In conclusion, we demonstrated that oral health status and behaviors were associated with hyperuricemia, especially in males. Further complementary studies are needed to confirm the definite association between oral health and hyperuricemia.

Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci1-8. Nevertheless, these loci only partially explain SLE heritability and provide limited biological insight. We report the largest study of SLE in East Asians (13,377 cases and 194,993 controls), identifying 233 association signals within 113 (46 novel) genetic loci. We detect six new lead missense variants and prioritize ten most likely putative causal variants, one of which we demonstrate exhibits allele-specific regulatory effect on ACAP1 in vitro. We suggest 677 effector genes with potential for drug repurposing, and provide evidence that two distinct association signals at a single locus act on different genes (NCF2 and SMG7). We demonstrate that SLE-risk variants overlap with cell-specific active regulatory elements, notably EBNA2-mediated super-enhancers in Epstein-Barr Virus-transformed B cells, and implicate the role for non-immune cells in SLE biology. These findings shed light on genetic and biological understandings of SLE.

ObjectiveGenome-wide association studies (GWAS) in rheumatoid arthritis (RA) have discovered over 100 RA loci, explaining patient-relevant RA pathogenesis but showing a large fraction of missing heritability. As a continuous effort, we conducted GWAS in a large Korean RA case–control population.MethodsWe newly generated genome-wide variant data in two independent Korean cohorts comprising 4068 RA cases and 36 487 controls, followed by a whole-genome imputation and a meta-analysis of the disease association results in the two cohorts. By integrating publicly available omics data with the GWAS results, a series of bioinformatic analyses were conducted to prioritise the RA-risk genes in RA loci and to dissect biological mechanisms underlying disease associations.ResultsWe identified six new RA-risk loci (SLAMF6, CXCL13, SWAP70, NFKBIA, ZFP36L1 and LINC00158) with pmeta−8 and consistent disease effect sizes in the two cohorts. A total of 122 genes were prioritised from the 6 novel and 13 replicated RA loci based on physical distance, regulatory variants and chromatin interaction. Bioinformatics analyses highlighted potentially RA-relevant tissues (including immune tissues, lung and small intestine) with tissue-specific expression of RA-associated genes and suggested the immune-related gene sets (such as CD40 pathway, IL-21-mediated pathway and citrullination) and the risk-allele sharing with other diseases.ConclusionThis study identified six new RA-associated loci that contributed to better understanding of the genetic aetiology and biology in RA.

To identify the prevalence of interstitial lung disease (ILD) in Korean patients with rheumatoid arthritis (RA) and assess its effect on mortality. A total of 3555 patients with RA, with chest X-ray or chest computed tomography (CT) data at enrollment were extracted from the KORean Observational study Network for Arthritis cohort, a nationwide prospective cohort for patients with RA in Korea. The patients were classified into two groups: (1) an ILD group by chest X-ray or chest CT scan, and (2) a non-ILD group by these modalities. After comparing the characteristics of the groups at enrollment, mortalities were compared using the log-rank test. To explore the impact of ILD on mortality, Cox proportional hazard models were used. Sixty-four patients (1.8%) were identified with ILD. Male and older patients were more common in the ILD group. During a mean follow-up of 24 months, 6 patients (9.4%) in the ILD group and 25 patients (0.7%) in the non-ILD group died; the survival rate was significantly worse in the ILD group (p

This study was supported by the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI10C2020). The authors wish to acknowledge the assistance of the following investigators who enrolled patients in KORONA: Joong Kyoung Ahn (Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul), Sung Jae Choi (Korea University Ansan Hospital, Ansan), Minyoung Her (Inje University Busan Paik Hospital, Busan), Chung- Il Joung (Konyang University Hospital, Daejeon), Young Mo Kang (Kyungpook National University Hospital, Daegu), Dong- Yook Kim (Inje University Busan Paik Hospital, Busan), Hae- Rim Kim (Konkuk University Medical Center, Seoul), Hyoun Ah Kim (Ajou University Hospital, Suwon), Choong Ki Lee (Yeungnam University Medical Center, Daegu), Sang- Hoon Lee (Kyung Hee University Hospital at Gangdong, Seoul), Seong- Su Nah (Soon Chun Hyang University Cheonan Hospital, Cheonan), Sung- Hoon Park (Catholic University of Daegu School of Medicine, Daegu), Dong Hyuk Sheen (Eulji University Hospital, Daejeon), Gwan Gyu Song (Korea University Guro Hospital, Seoul), Chang- Hee Suh (Ajou University Hospital, Suwon), and Yoo Wan- Hee (Chonbuk National University Hospital, Jeonju).

Background/Aims For patients with ankylosing spondylitis (AS), golimumab has consistent efficacy in controlling disease activity over 5 years but its benefit in preventing radiographic progression was less clear at 4 years. To predict radiographic progression, we analyzed the baseline characteristics of AS patients in a Korean population. Methods Sixty-eight Korean patients with AS participated in the phase 3, multicenter, randomized, placebo-controlled, double-blind trial (GO-RAISE) which has previously been described. Baseline modified stoke AS spine score (mSASSS) and change in mSASSS from baseline (ΔmSASSS) until week 208 were analyzed in the Korean patients enrolled in the GO-RAISE study. Results Although Korean patients had lower baseline mSASSS compared to non-Korean patients and received active management, radiographic progression was not prevented. Korean patients who did not undergo radiographic progression of spinal lesions of AS were younger and had shorter symptomatic duration, lower Bath AS functional and metrology indices, better chest expansion, and lower baseline mSASSS. The baseline mSASSS and ΔmSASSS were positively correlated in Korean AS patients (p < 0.001). Radiographic progression was more prevalent (80.0%) when baseline mSASSS > 10 and less common (13.0%) with baseline mSASSS = 0. Conclusions In Korean AS patients, radiographic progression of the spine after 4 years was predicted effectively by the initial severity of the spinal lesion(s) in patients treated with golimumab.

Background Diffusion-weighted imaging (DWI) is an MRI sequence and has been shown to have advantages over standard MRI sequences in some clinical settings, such as early diagnosis of ischemic stroke and in staging some type of cancers. Different measures of diffusion have been proposed, with the apparent diffusion coefficient (ADC) measure the most widely used. Severe Inflammation leads to higher ADC values through increased water in extracellular, less constrained, spaces. Several studies have investigated the clinical utility of DWI in AS, with suggestive evidence that this sequence has valuable discriminatory capacity between AS and non-inflammatory back pain by inflammation degree on sacroiliac joint (SIJ). Objectives This study was tested the potential capacity of ADC value estimated by DWI on SIJ as the predictor of new spinal syndesmophyte in young patients with ankylosing spondylitis (AS). Methods The 58 patients who fulfilled the ASAS axSpA criteria were enrolled and their age was 18-23 years old. All subjects underwent MRI on SIJ with oblique coronal images parallel to the long axis of the sacrum (fast spin-echo T1WI and STIR) at diagnosis and lumbar spine radiograph at diagnosis, 2 and 4 years sequentially. The ADC value on SIJ measured by DW-MRI at diagnosis and spinal radiographs were scored using the stoke AS Spinal Score (SASSS) at diagnosis, 2 and 4 years continuously. All patients were underwent a detailed clinical evaluation, including the serum erythrocyte sedimentation rate, C-reactive protein, BASDAI, BASMI and BASFI. The univariate and multivariate logistic regression analysis was performed to identify that ADC value on SIJ had an important influence on spinal syndesmophyte growth. Results The ADC value on SIJ showed a positive association with inflammatory marker such as, ESR and CRP, but no association with BASDAI, BASMI and BASFI. However, AS-DAS showed a positive association with ADC value. The high ADC value showed more strongly associated with high SASSS over 2 and 4 years continuously. The univariate logistics analysis showed ADC value and AS-DAS were significant predictors for new spinal syndesmophyte. However, multivariate logistics analysis showed the high ADC value had the highest risk of developing new syndesmophytes in spine. Conclusion This study showed that the inflammation of AS patient was a positive association with ADC value on SIJ by DW-MRI and the measured the ADC value on SIJ by DW-MRI was the modest discriminating capacity method for predicting development of new spinal syndesmophyte in young AS patients. References [1] Sequence in the Diagnosis of Ankylosing Spondylitis Diffusion-weighted Imaging Is a Sensitive and Specific Magnetic Resonance Robinson, Nivene Saad, Kim-Anh Le Cao and Matthew A. Brown Linda A. Bradbury, Kelly A. Hollis, Benoit Gautier, Sateesh Shankaranarayana, Philip C. J Rheumatol 2018;45;771-778 Acknowledgement None Disclosure of Interests None declared

To determine characteristics of rheumatoid arthritis (RA) patients in Korea using disease-modifying anti-rheumatic drugs (DMARDs) for at least 6 months, and to identify factors associated with poor health-related outcomes.A total of 2000 RA patients aged20 years, treated with DMARDs for at least 6 months, and signed informed consent, were enrolled in this non-interventional, multicenter, cross-sectional observational study from December 2012 to June 2013. Health-related quality of life (HRQoL) was measured using EuroQuol 5D (EQ-5D) and functional disability was measured using the Korean Health Assessment Questionnaire (KHAQ). Univariate and multivariate linear regression analyses were used to determine the association between patient characteristics and patient-reported outcomes (PROs).Of all RA patients, 84% were female, patients with low Disease Activity Score of 28 joints erythrocyte sedimentation rate (DAS-28-ESR3.2) was 54%, while moderate (DAS-28-ESR 3.2-5.1) and high disease activity score (DAS-28-ESR5.1) were 38% and 7.6%, respectively. Mean EQ-5D index score and KHAQ score were 0.6 ± 0.28 and 0.7 ± 0.67, respectively. In multivariate analysis with both PROs, average HRQoL and functional disability score appeared to be worse in persons with older age compared to younger age (P0.001), and worse in females compared to males (P0.001). Compared to patients having lower DAS (3.2), those with moderate and highest DAS (3.2-5.1 and5.1) had worse outcome measures (P0.001).In this study, higher DAS was one of the most influential factors for poor PROs among all other factors. Therefore, we could suggest appropriate treatment approaches according to DAS along with other significantly associated factors with PROs in the early stage of RA.

Remission is a primary end point of in clinical practice and trials of treatments for rheumatoid arthritis (RA). The 2011 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria were developed to provide a consensus definition of remission. This study aimed to assess the concordance between the new remission criteria and the physician’s clinical judgment of remission and also to identify factors that affect the discordance between these two approaches. A total of 3,209 patients with RA were included from the KORean Observational Study Network for Arthritis (KORONA) database. The frequency of remission was evaluated based on each approach. The agreement between the results was estimated by Cohen’s kappa (κ). Patients with remission according to the 2011 ACR/EULAR criteria (i.e. the Boolean criteria) and/or physician judgment (n = 855) were divided into three groups: concordant remission, the Boolean criteria only, and physician judgment only. Multinomial logistic regression analysis was used to identify factors responsible for the assignment of patients with remission to one of the discordant groups rather than the concordant group. The remission rates using the Boolean criteria and physician judgment were 10.5% and 19.9%, respectively. The agreement between two approaches for remission was low (κ = 0.226) and the concordant remission rate was only 5.5% (n = 177). Pain affected classification in both discordant groups, whereas fatigue was associated with remission only by physician clinical judgment. The Boolean criteria were more stringent than clinical judgment. Patient subjective symptoms such as pain and fatigue were associated with discordance between the two approaches., Graphical Abstract

To identify the level of agreement between patients with rheumatoid arthritis (RA) and physicians in the global assessment of disease activity and to explore factors influencing their discordance.A total of 4368 patients with RA were analyzed from the KORean Observational study Network for Arthritis (KORONA) database. Patients were divided into four subgroups according to difference from their physicians in the assessment of disease activity by substracting physician's visual analog scale (VAS) from patient's VAS as follows: positive discordance group I (10 mm ≤ discordance25 mm), positive discordance group II (≥25 mm), concordance (|10| mm), and negative discordance (≤ -10mm). Multinomial logistic regression analysis was performed to identify factors associated with discordance.Only 1350 (29.2%) patients were classified in the concordance group. Positive discordance was found in 52.3% of the patients (n = 2425), with 33.7% (n = 1563) showing marked discordance (≥25 mm). The high disease activity (OR =1.41), gastrointestinal (GI) disease (OR =1.28), pain (OR =1.12), fatigue (OR =1.07) were consistently associated with positive discordance.More than half of patients with RA thought their disease more severe than their physicians. In addition to high disease activity, pain, fatigue, and sleep disturbance or GI disease were associated with the discordance between physicians and patients with RA.

Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,478 SLE cases and 12,656 controls from six East Asian cohorts to identify new SLE susceptibility loci and better localize known loci. We identified ten new loci and confirmed 20 known loci with genome-wide significance. Among the new loci, the most significant locus was GTF2IRD1-GTF2I at 7q11.23 (rs73366469, Pmeta = 3.75 × 10(-117), odds ratio (OR) = 2.38), followed by DEF6, IL12B, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6. We identified the most likely functional variants at each locus by analyzing epigenetic marks and gene expression data. Ten candidate variants are known to alter gene expression in cis or in trans. Enrichment analysis highlights the importance of these loci in B cell and T cell biology. The new loci, together with previously known loci, increase the explained heritability of SLE to 24%. The new loci share functional and ontological characteristics with previously reported loci and are possible drug targets for SLE therapeutics.

Free fatty acids (FFAs), which are elevated with metabolic syndrome, are considered the principal offender exerting lipotoxicity. Few previous studies have reported a causal relationship between FFAs and osteoarthritis pathogenesis. However, the molecular mechanism by which FFAs exert lipotoxicity and induce osteoarthritis remains largely unknown. We here observed that oleate at the usual clinical range does not exert lipotoxicity while oleate at high pathological ranges exerted lipotoxicity through apoptosis in articular chondrocytes. By investigating the differential effect of oleate at toxic and nontoxic concentrations, we revealed that lipid droplet (LD) accumulation confers articular chondrocytes, the resistance to lipotoxicity. Using high fat diet-induced osteoarthritis models and articular chondrocytes treated with oleate alone or oleate plus palmitate, we demonstrated that articular chondrocytes gain resistance to lipotoxicity through protein kinase casein kinase 2 (PKCK2)—six-transmembrane protein of prostate 2 (STAMP2)—and fat-specific protein 27 (FSP27)-mediated LD accumulation. We further observed that the exertion of FFAs-induced lipotoxicity was correlated with the increased concentration of cellular FFAs freed from LDs, whether FFAs are saturated or not. In conclusion, PKCK2/STAMP2/FSP27-mediated sequestration of FFAs in LD rescues osteoarthritic chondrocytes. PKCK2/STAMP2/FSP27 should be considered for interventions against metabolic OA., Oil droplets protect cartilage from toxic fatty acids Cartilage tissue deals with the stress of exposure to free fatty acids by sequestering the toxic molecules into sub-cellular oil droplets. Young Hyun Yoo from Dong-A University College of Medicine in Busan, South Korea, and coworkers exposed rat cartilage cells to increasing levels of a fatty acid called oleate, a by-product of fat metabolism, and observed that the accumulation of oil droplets conferred resistance to oleate-induced toxicity. In these rat cells and in experiments involving mouse models of osteoarthritis fed a high-fat diet, the researchers then identified three of the protective proteins needed for cartilage tissue to properly quarantine fatty acids into oil droplets. Those proteins — and their connected regulatory networks — could now serve as drug targets for treating metabolic syndrome-associated osteoarthritis.

Free fatty acids (FFAs) are considered the principal inducers of lipotoxicity, leading to cell dysfunction and/or cell death. Lipotoxicity in Schwann cells (SCs) damages neurons, which may be associated with peripheral neuropathies and axon degeneration. However, the molecular mechanism by which FFAs exert lipotoxicity in SCs remains to be established. In the present study, we demonstrate that palmitate exerts lipotoxicity in SCs through apoptosis and that palmitate-induced lipotoxicity in SCs is mediated through reactive oxygen species (ROS) generation. We observed that the six-transmembrane protein of prostate 2 (STAMP2), which plays a pivotal role in lipid homeostasis, is expressed in SCs. We further demonstrate that palmitate induces lipoapoptosis in SCs through ROS generation-mediated STAMP2 downregulation and that STAMP2 depletion accelerates the palmitate-exerted lipoapoptosis in SCs, indicating that STAMP2 confers on SCs the ability to resist palmitate-induced lipotoxicity. In conclusion, palmitate induces lipoapoptosis in SCs through ROS generation-mediated STAMP2 downregulation. Our findings indicate that ROS and STAMP2 may represent suitable targets for pharmacological interventions targeting lipotoxicity-associated peripheral neuropathies and axon degeneration.

Background The predictor of radiographic spinal progression is the presence of syndesmophytes at baseline in axial spondyloarthritis (axSpA) and fat metaplasia on spine maybe predict the formation of new syndemophytes. Some studies suggests that fat metaplasia maybe a potential starting point for new bone formation and have a general systemic effect on new bone formation in spine, rather than results from local inflammation. Recent studies suggest that fat metaplasia on sacroiliac joint (SIJ) MRI at baseline is associated with spinal radiographic progression in axSpA patients. Objectives So in this study, we investigated for propensity to fat metaplasia on SIJ in axSpA patients. Methods The 357 patients who fulfilled the ASAS axSpA criteria were enrolled. All underwent MRI on SIj with T2 MR image, T1 fat suppressed with enhanced and short τ inversion recovery (STIR) image at baseline and lumbar spine radiographs at baseline and after 2 years. Inflammatory and structural lesions on SIJ MRI was scored using the SPondylo Arthritis Research Consortium of Canada (SPARCC) method. spinal radiographs were scored using the Stoke AS Spinal Score (SASSS). Multivariate logistic regression analysis was performed to identify for propensity to fat metaplasia on SIJ in axSpA patients. Results Among the 357 patients on baseline SIJ MRI finding, 182 patients showed fat metaplasia on SIJ, 148 patients showed erosion and 27 patients showed ankylosis. Propensity to fat metaplasia in axSpA patients showed the male, HLA-B27 negative, smoking, back pain onset time within 6–12 months at time of diagnosis, uveitis, peripheral arthritis, compared to erosion and anylosis on SIJ in axSpA patients. The patient with fat metaplasia or ankylosis on SIJ at baseline showed increased SASSS but there was no significant change in SPARCC over 2 years. univariate logistic regression analysis showed back pain onset time within 6–12 months at time of diagnosis and uvitis as a significant predictors of fat metaplasia. multivariated logistic analysis showed back pain onset time within 6–12 months at time of diagnosis as an affecting factor for fat metaplasia on SIJ (OR,5.67; 95% CI 4.71–17.95). Conclusions The back pain onset time within 6–12 months at time of diagnosis was affecting factor for propensity to fat metaplasia on SIJ in axSpA patients statistically and fat metaplasia on SIJ was associated with radiographic spinal progression in axSpA patients. so the early detection of fat metaplasia on SIJ in axSpA patients was important to protection of radiographic spinal progression. References [1] Maksymowych, et al. MRI evidence of structural changes in thesacroiliac joints of patients with nonradiographicaxial spondyloarthritis even in the absence of MRI inflammation. Arthritis Research & Therapy2017;19:126. [2] Fat Metaplasia on Sacroiliac Joint Magnetic Resonance Imaging at Baseline Is Associated with Spinal Radiographic Progression in Patients with Axial Spondyloarthritis. Plos oneaugust 2015 13. Acknowledgements none Disclosure of Interest None declared

Despite high clinical disease activity, some patients with active rheumatoid arthritis (RA) have normal acute phase reactant (APR) values. This study aimed to determine the clinical outcomes of active RA patients with normal APR values.Of 5376 patients with RA enrolled in the Korean observational study network for arthritis (KORONA) registry, 400 patients with disease duration of2 years who had Clinical Disease Activity Index (CDAI) score of2.8 at baseline, biologic-naïve, and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) drawn at both baseline and 2-year follow-up visits were identified. Patients were grouped according to baseline APR levels: normal APRs, one APR elevated, and both APRs elevated.Baseline tender and swollen joint counts, mean CDAI and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores were significantly lower in the normal APRs group compared with APR-elevated groups (P 0.0001). At 2-year follow-up, mean CDAI scores, HAQ-DI, and percentage of the patient achieving remission were not significantly different between the normal APRs group compared with the APR-elevated groups regardless of the baseline disease activity. However, in patients with baseline CDAI moderate to high disease activity, the normal APRs group less frequently required initiation of the biologic disease-modifying anti-rheumatic drugs compared with the APR-elevated groups (P = 0.044).Active RA patients with normal APR values have milder disease presentation, but similar clinical outcomes to those with elevated APRs.

Recent studies have shown that a combination treatment of mycophenolate mofetil (MMF) and tacrolimus (TAC) may be an option for lupus nephritis (LN) patients that do not adequately respond to initial treatment. We evaluated the efficacy and safety of the combination treatment of MMF and TAC in LN patients with suboptimal response to prior MMF or TAC treatments.In this multicentre study, we retrospectively enrolled 62 patients with class III, IV, or V LN who inadequately responded to MMF or TAC treatment. Those patients were then treated with a combination of MMF and TAC for 6 months. The primary outcome was complete remission (CR) at 6 months, and secondary outcomes included overall response and adverse events.After 6 months of treatment with the drug combination, CR was achieved in 14 of 62 patients (22.6%), and 35 (56.5%) patients responded. A significant reduction in proteinuria and lupus disease activity score was observable after 3 months. After 1 year, the CR rate increased to 36.4% (20 of 55 patients), and the overall response rate (n=38, 69.1%) also increased from 6 months. Twenty-one patients reported 29 adverse events, including severe infection requiring hospitalisation (n=3, 10.3%), infection not requiring hospitalisation (n=2, 6.9%), and herpes zoster (n=4, 13.8%).Our findings suggest that a combined MMF and TAC treatment, with a favourable adverse-event profile, may be a beneficial option for LN patients with inadequate response to either MMF or TAC treatments.

Background The polarization of macrophages was the expressed to M1/M2 phenotype by various stimuli or environment signals. The M1 macrophage was pro-inflammatory phenotype and was key effector cells in the immune response of rheumatoid arthritis (RA). So, M1 macrophage influenced the inflammation of RA synovial membrane and joint destruction in RA, whereas M2 macrophage was anti-inflammatory phenotype and could down-regulate the production of proinflammatory cytokines in RA. The SIRT1 attenuated the RA inflammation via down-regulation of NF-κB signaling. However, the effect of SIRT1 on macrophages polarization remained uncler. Objectives We aimed to check out that activated SIRT1 modulated macrophages polarization into M1 phenotype and controlled the inflammation of RA. Methods Monocytes from synovial fluid of RA patients, bone marrow–derived monocytes (BMDCs) from mice were studied. monocytes were cultured with M-CSF for 7days to differentiate into M0 macrophages (monocyte-derived mature macrophages M0 phenotype). M0 macrophages were incubated with LPS and IFN-gamma in order to obtain M1 macrophages. M1 macrophage markers were detected by real-time PCR. Results Activation of SIRT1 was achieved by Resveratrol, activated SIRT1 attenuated M1 macrophage phenotypes and pro-inflammatory cytokine expression. macrophages obtained from SIRT1-tg mice, which were overexpression of SIRT1, exhibited decreased M1 markers in association with enhanced activation of AMPK/ACC compared with macrophage from control C57BL/6 mice. In addition to SIRT1 activation, M1 polarizing signal, acetylation of NF-κB p65, was suppressed. In SIRT1-deficient macrophages, resveratrol fail to increase AMPK activity and to decrease the expression M1 markers owing to enhanced acetylation of NF-κB p65. Conclusions SIRT1 maybe an important modulator of M1 macrophages polarization and increased AMPK activity, which suppressed acetylation of NF-κB p65 during inflammation of RA. so, modulation of SIRT1 maybe a new target in RA treatment. References SIRT1 inhibits differentiation of monocytes to macrophages: amelioration of synovial inflammation in rheumatoid arthritis. J Mol Med (Berl). 2016 Aug;94(8):921–31. Disclosure of Interest None declared

The purpose of this study was to identify the characteristic magnetic resonance imaging (MRI) findings in neuropsychiatric systemic lupus erythematosus (NPSLE) and to investigate the association between MRI findings and neuropsychiatric manifestations in SLE. Brain MRIs with a diagnosis of SLE from 2002 to 2013 from three tertiary university hospitals were screened. All clinical manifestations evaluated by brain MRI were retrospectively reviewed. If the clinical manifestations were compatible with the 1999 NPSLE American College of Rheumatology (ACR) nomenclature and case definitions, the brain MRIs were assessed for the presence of white matter hyperintensities, gray matter hyperintensities, parenchymal defects, atrophy, enhancement, and abnormalities in diffusion-weighted images (DWI). The number, size, and location of each lesion were evaluated. The neuropsychiatric manifestation of each brain MRI was classified according to the 1999 ACR NPSLE case definitions. The associations between MRI findings and NPSLE manifestations were examined. In total, 219 brain MRIs with a diagnosis of SLE were screened, and 133 brain MRIs met the inclusion criteria for NPSLE. The most common MRI abnormality was white matter hyperintensities, which were observed in 76 MRIs (57.1 %). Gray matter hyperintensities were observed in 41 MRIs (30.8 %). Parenchymal defects were found in 31 MRIs (23.3 %), and atrophy was detected in 20 MRIs (15.0 %). Patients who had seizures were more associated with gray matter hyperintensities than patients with other neuropsychiatric manifestations. Patients with cerebrovascular disease were more associated with gray matter hyperintensity, parenchymal defects, and abnormal DWI than patients with other neuropsychiatric manifestations. In addition to white matter hyperintensities, which were previously known as SLE findings, we also noted the presence of gray matter hyperintensities, parenchymal defects, and abnormal DWI in a substantial portion of SLE patients, particularly in those with cerebrovascular disease or seizures.

Objective. Evaluate effectiveness/safety of tacrolimus in patients in Korea with active rheumatoid arthritis (RA) and unsuccessful response to disease-modifying anti-rheumatic drugs (DMARDs). Methods. Open-label, single-arm, non-comparative, 24-week, Phase-IV study in patients with active RA who had taken DMARDs for ＞6 months. Following a washout period, tacrolimus was initiated (baseline-12 weeks; dose 2 mg/day and 1.5 mg/day in patients aged ≤65 and ＞65 years, respectively). After 12 weeks, dose could be adjusted (remaining between 1~3 mg); treatment continued to 24 weeks. Primary endpoint was American College of Rheumatology 20% improvement (ACR20) (baseline-Week 24). Secondary endpoints included ACR50/ACR70 response, disease-activity score in 28 joints (DAS28) erythrocyte sedimentation rate (ESR), number of tender/ swollen joints, and bone mineral density (BMD) loss. Adverse events (AEs) were recorded. Results. Overall, 121 patients were analysed. Mean ±standard deviation tacrolimus dose baseline-Week 24 was 1.81±0.47 mg/day. After 24 weeks, 64.5%, 39.7%, and 19.0% of patients were ACR20, ACR50, and ACR70 responders, respectively. DAS28-ESR score decreased from 5.5±0.8 (baseline) to 3.7±1.5 (Week 24; p＜0.0001); number of tender/swollen joints decreased. Between screening and Week 24, change in BMD-T score in lumbar and femur regions was -0.06±0.38 (p=0.1550) and -0.04±0.28 (p=0.0936), respectively, with no significant change in International Society for Clinical Densitometry classification. Fifty-six (46.3%) patients experienced 93 AEs; 75.3% were mild. No unexpected safety signals identified. Conclusion. Tacrolimus therapy was associated with a high proportion of ACR responders, and improved DAS28-ESR score and physical joint function during the study. Tacrolimus may be a suitable therapy for DMARD-resistant patients with RA. (J Rheum Dis 2019;26:20-30)

To compare the clinical effectiveness of two treatment strategies for active rheumatoid arthritis (RA) refractory to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs): starting TNF inhibitors (TNFIs) or changing csDMARDs.We used two nationwide Korean RA registries for patient selection. TNFI users were selected from the BIOPSY, which is an inception cohort of RA patients starting biologic DMARDs. As a control group, we selected RA patients with moderate or high disease activity from the KORONA database whose treatment was changed to other csDMARDs. After comparing baseline characteristics between the two groups in either unmatched or propensity score matched cohorts, we compared potential differences in the 1-year remission rate as a primary outcome and changes in HAQ-DI and EQ-5D scores as secondary outcomes.A total of 356 TNFI starters and 586 csDMARD changers were identified from each registry as unmatched cohorts, and 294 patients were included in the propensity score matched cohort. In the intention-to-treat analysis, TNFI starters had higher 1-year remission rates than csDMARD changers in both unmatched (19.1 vs. 18.4%, p 0.01) and matched cohorts (19.7 vs. 15.0%, p 0.01). In per protocol analysis, TNFI starters had much higher remission rates in unmatched (37.2 vs. 28.0%, p = 0.04) and matched cohorts (35.4 vs. 19.1%, p = 0.04). However, in matched cohorts, no significant differences were observed between two groups in HAQ-DI and EQ-5D scores.We compared the clinical effectiveness of the two treatment strategies for active RA refractory to csDMARDs. TNFI starters showed higher 1-year remission rates than csDMARD changers.

The aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects. This study enrolled a total of 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142(C>A) in the P2X7R gene and rs2043211(A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses. A difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (P > 0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed that subjects with the CA P2X7R rs3751142 genotype and the TT CARD8 rs2043211 genotype had a trend toward a higher risk of gout compared to the CC/AA combination (P = 0.056, OR = 2.618, 95% CI 0.975 - 7.031). In conclusion, this study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout., Graphical Abstract

The genetic association of HLA-DRB1 with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is well documented, but association with other HLA-DR beta genes (HLA-DRB3, HLA-DRB4 and HLA-DRB5) has not been thoroughly studied, despite their similar functions and chromosomal positions. We examined variants in all functional HLA-DR beta genes in RA and SLE patients and controls, down to the amino-acid level, to better understand disease association with the HLA-DR locus. To this end, we improved an existing HLA reference panel to impute variants in all protein-coding HLA-DR beta genes. Using the reference panel, HLA variants were inferred from high-density SNP data of 9,271 RA-control subjects and 5,342 SLE-control subjects. Disease association tests were performed by logistic regression and log-likelihood ratio tests. After imputation using the newly constructed HLA reference panel and statistical analysis, we observed that HLA-DRB1 variants better accounted for the association between MHC and susceptibility to RA and SLE than did the other three HLA-DRB variants. Moreover, there were no secondary effects in HLA-DRB3, HLA-DRB4, or HLA-DRB5 in RA or SLE. Of all the HLA-DR beta chain paralogs, those encoded by HLA-DRB1 solely or dominantly influence susceptibility to RA and SLE.

Although alpha alpha B-crystallin is expressed in articular chondrocytes, little is known about its role in these cells. Protein kinase casein kinase 2 (CK2) inhibition induces articular chondrocyte death. The present study examines whether alpha B-crystallin exerts anti-apoptotic activity in articular chondrocytes. Primary rat articular chondrocytes were isolated from knee joint slices. Cells were treated with CK2 inhibitors with or without alpha B-crystallin si RNA. To examine whether the silencing of aB-crystallin sensitizes rat articular chondrocytes to CK2 inhibition induced apoptosis, we assessed apoptosis by performing viability assays, mitochondrial membrane potential measurements, flow cytometry, nuclear morphology observations, and western blot analysis. To investigate the mechanism by which aB-crystallin modulates the extent of CK2 inhibition-mediated chondrocyte death, we utilized confocal microscopy to observe the subcellular location of aB-crystallin and its phosphorylated forms and performed a co-immunoprecipitation assay to observe the interaction between aB-crystallin and CK2. Immunochemistry was employed to examine aB-crystallin expression in cartilage obtained from rats with experimentally induced osteoarthritis (OA). Our results demonstrated that silencing of aB-crystallin sensitized rat articular chondrocytes to CK2 inhibitor -induced apoptosis. Furthermore, CK2 inhibition modulated the expression and subcellular localization of aB-crystallin and its phosphorylated forms and dissociated aB-crystallin from CK2. The population of rat articular chondrocytes expressing aB-crystallin and its phosphorylated forms was reduced in an experimentally induced rat model of OA. In summary, aB-crystallin protects rat articular chondrocytes against CK2 inhibition -induced apoptosis. aB-crystallin may represent a suitable target for pharmacological interventions to prevent OA.

Considerable sharing of disease alleles among populations is well-characterized in autoimmune disorders (e.g., rheumatoid arthritis), but there are some exceptional loci showing heterogenic association among populations. Here we investigated genetic variants with distinct effects on the development of rheumatoid arthritis in Asian and European populations. Ancestry-related association heterogeneity was examined using Cochran’s homogeneity tests for the disease association data from large Asian (n = 14,465; 9,299 discovery subjects and 5,166 validation subjects; 4 collections) and European (n = 45,790; 11 collections) rheumatoid arthritis case-control cohorts with Immunochip and genome-wide SNP array data. We identified significant heterogeneity between the two ancestries for the common variants in the GTF2I locus (PHeterogeneity = 9.6 × 10−9 at rs73366469) and showed that this heterogeneity was due to an Asian-specific association effect (ORMeta = 1.37 and PMeta = 4.2 × 10−13 in Asians; ORMeta = 1.00 and PMeta = 1.00 in Europeans). Trans-ancestral comparison and bioinfomatics analysis revealed a plausibly causal or disease-variant-tagging SNP (rs117026326; in linkage disequilibrium with rs73366469), whose minor allele is common in Asians but rare in Europeans. In conclusion, we identified largest-ever effect on Asian rheumatoid arthritis across human non-HLA regions at GTF2I by heterogeneity mapping followed by replication studies, and pinpointed a possible causal variant.

A 57-year-old man with rheumatoid arthritis presented severe abdominal pain symptomatic of panperitonitis. Computer tomography findings were consistent with vasculitis on the jejunum. Confirmatory angiography was conducted. Since abdominal vasculitis in rheumatoid arthritis is very rare, early diagnosis and treatment should be done according to clinical manifestation. In this case, high-dose steroid treatment was applied based on clinical manifestation, laboratory findings, and radiologic finding. After therapy, clinical manifestation and flare-up arthritis diminished.

To identify the clinical features of elderly-onset rheumatoid arthritis (EORA) and their impact on disease outcome.A total of 3169 rheumatoid arthritis (RA) patients were recruited as part of the Korean Observational Study Network for Arthritis, the nationwide cohort of South Korea. Patients were stratified according to age at disease onset:40 years (younger age-onset RA, n = 1167), between the ages of 40 and 59 (middle-aged-onset RA, n = 1516), and ≥60 years (EORA, n = 486). To evaluate the significance of differences in clinical features among these 3 groups, we performed analysis of variance (anova) and the χ(2) test. We used multivariable logistic regression analysis to examine the association of onset age with functional disability measured with Health Assessment Questionnaire-Disability Index (HAQDI).EORA patients were associated with high HAQDI (≥1) in bivariable analysis [odds ratio (OR) 1.36, confidence interval (CI) 1.04-1.77]. However, in multivariable analysis, not elderly onset but patients' age, female gender, high disease activity, disease duration over 10 years, and comorbidity with cardiovascular disease were associated with high HAQDI. Only in a predefined subgroup with disease duration10 years, elderly onset was an independent influencing factor for the functional disability of RA patients (OR 3.04, CI 1.85-5.67: disease duration of5 years, OR 3.07, CI 1.64-5.74: disease duration of 5 to 10 years).Disease onset in older age was associated independently with functional disability of RA patients who have relatively short disease duration.

Rationale Dystrophic calcinosis occurs in chronically damaged tissue in patients with complicated autoimmune diseases. The therapeutic options are limited, and the treatment response rate is variable. Here, we describe a rare case of dystrophic calcinosis treated with leflunomide in a patient with overlap syndrome. Patient concerns A 53-year-old woman who was diagnosed with overlaps syndrome (systemic sclerosis [SSc] with rheumatoid arthritis [RA]), presented to our hospital with pain and swelling in both wrists, and underwent radiography, bone scan, and biopsy examination. Diagnoses This patient was diagnosed with dystrophic calcinosis in overlaps syndrome. Interventions The conventional disease-modifying drugs were not effective. Hence, leflunomide was administered. Outcomes Simple radiography and bone scan showed resolved mass-like dystrophic calcinosis on both wrists of the patient after the use of leflunomide. Lessons The control of underlying disease is important in the treatment of dystrophic calcinosis. The use of leflunomide maybe an option in treatment of dystrophic calcinosis combined with RA.

This study was designed to identify susceptibility to insulin resistance and the association of serum resistin and adiponectin with insulin resistance in patients with Behçet's disease (BD). Also, we identify risk determinants for insulin resistance in BD patients.The study population consisted of 82 BD patients (n = 26 males) and 89 healthy controls (n = 40 males). Clinical data were collected at the time of enrollment, and serum resistin and adiponectin levels were measured using enzyme-linked immunosorbent assays. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated by measuring fasting plasma glucose and insulin levels.BD patients and healthy controls differed significantly in insulin resistance (HOMA-IR) (1.3 +/- 1.1 vs. 0.7 +/- 0.5, p0.001) and serum resistin level (7901.7 +/- 1314.9 vs. 7444.2 +/- 1841.6, p = 0.001) but not in serum adiponectin level (p = 0.223). No differences in HOMA-IR, serum adiponectin, and serum resistin were found between patients with active and inactive BD. It is determined that plasma glucose, plasma insulin, and serum resistin may be determinant for the HOMA-IR. The number of metabolic syndrome components is closely correlated with HOMA-IR in BD patients (r = 0.245, p = 0.029).This study demonstrates that there is an increased susceptibility to insulin resistance in patients with BD as compared to healthy controls. Serum resistin level may be an independent determinant for insulin resistance in BD patients.

Objective To assess the effects of cilostazol in inhibiting proliferation and enhancing apoptosis in synovial cells from patients with rheumatoid arthritis (RA). Methods Synovial cell proliferation was measured by MTT assay. The expression of NF-κB, IκBα, Bcl-2, Bax, heme oxygenase 1 (HO-1), and Nrf2 was determined by Western blotting. Results Cilostazol suppressed synovial cell proliferation by arresting the G2/M phases of the cell cycle, and this was reversed by KT5720, an inhibitor of protein kinase A. Cilostazol increased the number of TUNEL-positive cells, with increased cytochrome c release and apoptosis-inducing factor translocation as well as increased caspase 3 activation. Cilostazol (10 μM) and cobalt protoporphyrin IX (CoPP) increased HO-1 messenger RNA and protein expression. These effects were suppressed by zinc protoporphyrin IX (ZnPP), an HO-1 inhibitor. Cilostazol and CoPP significantly increased IκBα in the cytosol and decreased NF-κB p65 expression in the nucleus. Increased expression of tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), and IL-6 induced by lipopolysaccharide was attenuated by cilostazol and CoPP, and this was reversed by ZnPP. In mice with collagen-induced arthritis treated with cilostazol (10 and 30 mg/kg/day), paw thickness was decreased with increased apoptotic cells in the joints. In synovial cells transfected with small interfering RNA (siRNA) targeting HO-1, cilostazol did not suppress expression of TNFα, IL-1β, and IL-6, in contrast to findings with negative control cells. Cilostazol- and CoPP-induced HO-1 expression was diminished in cells transfected with Nrf2 siRNA. Conclusion Cilostazol suppressed proliferation of synovial cells from RA patients by enhancing apoptosis, and also inhibited cytokine production via mediation of cAMP-dependent protein kinase activation–coupled Nrf2-linked HO-1 expression.

Background : The presence of antiphospholipid antibodies (aPLs) is associated with the clinical features of antiphospholipid syndrome (APS), which comprises venous and arterial thrombosis and pregnancy loss, and systemic lupus erythematosus (SLE). The prevalence of aPLs has been reported to be different in patient populations affected by either of these conditions. We performed a retrospective study to evaluate the prevalence and clinical associations of aPLs, including lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) in a cohort of Korean patients with SLE. Methods : This study included samples from 88 SLE patients for whom aPL testing had been advised between June 2006 and July 2009 at the Dong-A University Hospital. Serum and plasma samples were tested for LAC, aCL (IgG, IgM), and anti-beta2-GPI (IgG, IgM) antibodies. Clinical data from patients were obtained from a review of medical records. Results : LAC was the most common (34.1% of total patients, 30/88) antibody, followed by IgM aCL (31.8%, 28/88), IgG aCL (18.2%, 16/88), and IgM and IgG anti-beta2-GPI (both 5.7%, 5/88 each). Positivity for LAC was strongly associated with venous/arterial thrombosis (P=0.002). Conclusions : LAC was the most common antibody detected in Korean SLE patients and is shown to have a significant association with the presence of venous/arterial thrombosis. The measurement of LAC may be clinically useful in identifying patients with SLE who are at a high risk for venous/arterial thrombosis. (Korean J Lab Med 2010;30:38-44)

Objective. To estimate the prevalence of non-adherence to rheumatoid arthritis (RA) medication and identify the associated factors for non-adherence in RA patients. Methods. Among the KORean Observational study Network for Arthritis 3,523 patients who completed a questionnaire about the adherence to RA medication were analyzed. The patients were divided into two groups: 1) adherent group, patients who skipped medication ≤5 days within the past 2 months; and 2) non-adherent group, patients who skipped ≥6 days of medication. The baseline characteristics were compared, and multivariable regression analysis was performed to identify the associated factors for non-adherence. Results. The non-adherent group had 339 patients (9.6%). The common causes of non-adherence were forgetfulness (45.8%), absence of RA symptoms (24.7%), and discomfort with RA medication (13.1%). Younger age (odds ratio [OR] 1.02, p＜0.01) and higher income (OR 1.70, p＜0.01) were associated with an increased risk of non-adherence. Whereas higher functional disability (OR 0.68, p＜0.01) and oral corticosteroid use (OR 0.73, p=0.02) were associated with a decreased risk of non-adherence. The associated factors differed according to cause of non-adherence. Having adverse events (OR 2.65, p=0.02) was associated with the risk of non-adherence due to discomfort with RA medication while a higher level of education (OR 2.37, p=0.03) was associated with the risk of non-adherence due to an absence of RA symptoms. Conclusion. The 9.6% of Korean RA patients were non-adherent to RA medication. The associated factors differed according to the cause of non-adherence. Therefore, an individualized approach will be needed to improve the adherence to RA medication. (J Rheum Dis 2018;25:47-57)

Aim: To investigate the distribution of human leucocyte antigen (HLA) class I antigens and B27 subtypings in a group of B27(+) ankylosing spondylitis (AS) patients and a group of B27(+) control individuals, and to compare differences in their clinical features using subtyping. Methods: At otal of 143 B27(+) AS samples and 32 B27(+) control samples were collected consecutively from two rheumatology centres in South Korea. All patients were diagnosed according to the modified New York criteria for AS. Medical records of the patients were retrospectively reviewed for demographic information, Bath disease activity index (BASDAI) scores, laboratory parameters at diagnosis and extra-articular manifestations. Polymerase chain reaction-sequence-specific primer typing for the B27 subtypes was performed using the Dynal HLA-B27 high resolution kit. Results: Whereas subtypes in Korean AS patients include B*2704 (n = 11, 7.7%) B*2705 (n = 130, 90.9%), and B*2710 (n = 2, 1.4%), those of the control groups include B*2704 (n = 11, 34.4%), B*2705 (n = 19, 59.4%), B*2710 (n = 1, 3.1%), and B*2715 (n = 1, 3.1%). The proportion of B*2705 subtypes were significantly higher in the AS group than the control group (P

Objective.Fcγreceptors (FcγR) have important functions in the regulation of immune response and clearance of immune complex. High levels of immunoglobulins have been observed in patients with the active stage of adult onset Still’s disease (AOSD), and high-dose intravenous immunoglobulin treatment has decreased the disease activity of AOSD. We investigated polymorphisms of FcγR as genetic factors influencing susceptibility or disease course of AOSD in Korea.Methods.We genotyped the FcγRIIA H/R131, IIIA F/V176, and IIIB NA1/NA2 loci in 98 patients with AOSD and 151 healthy controls. Genotyping was performed using sequence-specific PCR. Patients with AOSD were subdivided into groups according to disease course: monocyclic systemic, polycyclic systemic, or chronic articular type. Allelic, genotypic, and haplotypic associations were analyzed by chi-square test.Results.No significant skewing in any of the 3 FcγR polymorphisms was found between Korean AOSD patients and controls. FcγRIIA R/R131 and R/H131 genotype in patients with chronic articular-type disease was more frequent than in controls (p = 0.006 and pcorr = 0.018). No differences of genotypic and allelic frequencies were found between other disease course types and controls. Haplotype IIA R131-IIIA F176-IIIB NA2 was more frequent in AOSD patients than in controls (p = 0.021).Conclusion.Although FcγR polymorphisms are not associated with development of AOSD in Koreans, the haplotype IIA R131-IIIA F176-IIIB NA2 may be associated with AOSD. Also, the FcγRIIA polymorphism may be associated with chronic articular-type AOSD. We need to identify whether these polymorphisms are associated with a response to anti-tumor necrosis factor agents in patients with AOSD.

Aim: To investigate the role of TNF-α promoter polymorphisms in the pathogenesis of Korean adult-onset Still's disease (AOSD) patients. Methods: DNA was isolated from blood samples collected from 58 patients with AOSD meeting Yamaguchi's criteria and 105 healthy controls. TNF-αpromoter polymorphisms at positions –1013, –863, –857, –308 were analysed by polymerase chain reaction-restriction fragment length polymorphism method. Genotype, allele, and estimated haplotype frequencies were compared between the AOSD group and controls. Results: The genotype, allele distributions, and estimated haplotype frequencies of the TNF-αpolymorphism between AOSD patients and controls were not significantly different. In addition, TNF-αpolymorphisms did not appear to have an effect on the disease course of the Korean AOSD patients. Conclusion: Genetic polymorphisms of TNF-αdo not play a significant role in the development or in their course of Korean AOSD patients.

We investigated the effects oftai chion disease activity, flexibility and depression in patients with ankylosing spondylitis (AS). We allocated 40 patients to either atai chitreatment group or a no-treatment control group. Thetai chigroup performed 60 min oftai chitwice weekly for eight consecutive weeks and 8 weeks of home-basedtai chi, after which the group showed significant improvement in disease activity and flexibility compared to the control group. All outcome measures were significantly lower in thetai chigroup than they were during pre-treatment, while they did not change in the control group. These findings suggest thattai chican improve disease activity and flexibility for patients with AS.Tai chiis an easily accessible therapy for patients and, as such, may be an effective intervention for AS. However, we cannot completely discount the possibility that the placebo effect was responsible for the improvement.