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Toll-like receptor (TLR)-4 and TLR9 are known to play important roles in the immune system, and several studies have shown their association with the development of rheumatoid arthritis (RA) and regulation of tumor necrosis factor alpha (TNF-α). However, studies that investigate the association between TLR4 or TLR9 gene polymorphisms and remission of the disease in RA patients taking TNF-α inhibitors have yet to be conducted. In this context, this study was designed to investigate the effects of polymorphisms in TLR4 and TLR9 on response to TNF-α inhibitors and to train various models using machine learning approaches to predict remission. A total of six single nucleotide polymorphisms (SNPs) were investigated. Logistic regression analysis was used to investigate the association between genetic polymorphisms and response to treatment. Various machine learning methods were utilized for prediction of remission. After adjusting for covariates, the rate of remission of T-allele carriers of TLR9 rs352139 was about 5 times that of the CC-genotype carriers (95% confidence interval (CI) 1.325–19.231, p = 0.018). Among machine learning algorithms, multivariate logistic regression and elastic net showed the best prediction with the area under the receiver-operating curve (AUROC) value of 0.71 (95% CI 0.597–0.823 for both models). This study showed an association between a TLR9 polymorphism (rs352139) and treatment response in RA patients receiving TNF-α inhibitors. Moreover, this study utilized various machine learning methods for prediction, among which the elastic net provided the best model for remission prediction.

Objectives Nuclear factor of activated T cells C2 (NFATC2) is known as a member of the transcription family and enhances tumor necrosis factor-alpha (TNF-α) synthesis in human T cells at the gene transcription level. Although NFATC2 has a potential role in rheumatoid arthritis (RA) progression and treatment, no study has investigated the association between NFATC2 gene polymorphisms and response status in RA patients receiving TNF-α inhibitors. This study aimed to examine the effects of polymorphisms in NFATC2, a TNF-α transcription factor, on response to TNF-α inhibitors. Methods This prospective observational study was performed in two centers. Seven single nucleotide polymorphisms (SNPs) were investigated. Good responders were defined as patients with disease activity score (DAS)28 ≤3.2 after 6 months of treatment. Logistic regression analyses were used to investigate the association between genetic polymorphisms and response to the treatment. To test the model's goodness of fit, a Hosmer-Lemeshow test was performed. Results This study included 98 patients, among whom 46 showed favorable responses to the treatment. Patients with hypertension revealed an approximately three-fold lower response to TNF-α inhibitors compared to those without hypertension (23.5 vs. 76.5%; P = 0.049). After adjusting for covariates, C allele carriers of NFATC2 rs3787186 exhibited approximately three-fold lower rates of treatment response compared to those with TT genotype (P = 0.037). The Hosmer-Lemeshow test showed that the fitness of the multivariable analysis model was satisfactory (χ2 = 9.745; 8 degrees of freedom; P = 0.283). Conclusion This study suggested an association between the C allele of rs3787186 and treatment response in RA patients receiving TNF-α inhibitors.

Objectives Osteoporosis and fracture are known complications of systemic lupus erythematosus (SLE). We assessed the prevalence and risk factors for osteoporosis in patients with SLE. Methods A total of 155 female SLE patients were recruited retrospectively in 5 university hospitals. The bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry, and the fracture risk assessment tool (FRAX) for high-risk osteoporotic fractures was calculated with and without BMD. Results The mean age was 53.7 ± 6.8 years, and osteoporotic fractures were detected in 19/127 (15.0%) patients. The proportion of patients having a high-risk for osteoporotic fractures in the FRAX with and without BMD, and osteoporosis by the World Health Organization (WHO) criteria were 25 (16.1%), 24 (15.5%), and 51 (32.9%), respectively, and 48.0–68.6% of them were receiving treatment. On multivariate logistic analysis, nephritis (odds ratio [OR] 11.35) and cumulative dose of glucocorticoid (OR 1.1) were associated with high-risk by the FRAX with BMD, and low complement levels (OR 4.38), erythrocyte sedimentation rate (ESR) (OR 1.04), and cumulative dose of glucocorticoid (OR 1.05) were associated with osteoporosis by the WHO criteria in patients with SLE. Conclusions Among Korean female patients with SLE, the proportion of patients having a high-risk of osteoporotic fractures by the FRAX tool was 15.5%–16.1% and the proportion of patients having osteoporosis by the WHO criteria was 32.9%. In SLE, nephritis, low level of complement, ESR, and cumulative dose of glucocorticoids may contribute to fracture risk.

Polymyalgia rheumatica (PMR), a benign rheumatic disorder, requires long-term glucocorticoid therapy, which could be associated with osteoporosis. In the present study, we compared bone mineral density (BMD), trabecular bone score (TBS) and frequencies of vertebral fracture (VF) among patients with PMR or rheumatoid arthritis (RA) and controls.Fifty-three postmenopausal women with PMR aged 50 yr or older were eligible for inclusion in this study. Subjects in RA (n = 106) and control (n = 106) groups were selected by propensity score matching with controlling age, body mass index and use of anti-osteoporotic agents.The frequency of VF in patients with PMR (30.2%) was significantly higher than those in patients with RA (13.2 %) and controls (13.2%, p = 0.017). The mean TBS of patients with PMR (1.317 ± 0.092) was significantly lower than those of patients with RA (1.336 ± 0.089) and the controls (1.373 ± 0.073, p0.001). In receiver operating characteristic analysis for VF in patients with PMR, the area under the curve (AUC) was 0.759 (95% confidence interval [CI] = 0.601-0.918, p0.001) for TBS and 0.618 (95% CI = 0.442-0.795, p0.001) for L-spine BMD. The AUCs were 0.760 (95% CI = 0.630-0.891, p ≤ 0.001) and 0.767 (95% CI 0.627-0.907, p0.001) for femur neck and total hip BMD, respectively. Multivariate analysis identified the factor associated with VF of patients with PMR as a lower TBS (Odds ratio: 0.000, 95% CI: 0.000, 0.754, p = 0.043).TBS could be a supplementary tool for discriminating osteoporotic fractures in postmenopausal patients with PMR.

Purpose TNF-α is a transmembrane protein which requires cleavage by ADAM17 in order to act systemically. The activation of ADAM17 to generate soluble TNF‑α results in an increased inflammatory activity. We hypothesized that variants spanning the ADAM17 gene contribute towards the observed variation in patient response defined by the number of changes in TNF‑α inhibitors. Patients and methods Seven single-nucleotide polymorphisms (SNPs) of ADAM17 in 63 patients with rheumatoid arthritis who received TNF-α inhibitors were analyzed: rs57467365, rs62117540, rs117645314, rs6432013, rs532704607, rs117179141, and rs12692386. Univariate and multivariate regression analysis were employed to investigate the independent predictable factors for changes in TNF-α inhibitors. Results ADAM17 rs117645314 and rs117179141 showed significant association with the number of changes in TNF-α inhibitors. Patients with GA in rs117645314 and AT in rs117179141 had significantly higher chance of two or more changes of TNF-α inhibitors than those with wild homozygous alleles. Multivariate analysis showed that rs117179141 explained 5.7% of the 23.8% variability in TNF-α inhibitor response. Conclusion This study showed that the number of changes in TNF-α inhibitor is associated with ADAM17 SNPs.

Neutrophils are innate immune phagocytes that play a key role in immune defense against invading pathogens. The main offensive mechanisms of neutrophils are the phagocytosis of pathogens, release of granules, and production of cytokines. The formation of neutrophil extracellular traps (NETs) has been described as a novel defense mechanism in the literature. NETs are a network of fibers assembled from chromatin deoxyribonucleic acid, histones, and neutrophil granule proteins that have the ability to kill pathogens, while they can also cause toxic effects in hosts. Activated neutrophils with NET formation stimulate autoimmune responses related to a wide range of inflammatory autoimmune diseases by exposing autoantigens in susceptible individuals. The association between increased NET formation and autoimmunity was first reported in antineutrophil cytoplasmic antibody-related vasculitis, and the role of NETs in various diseases, including systemic lupus erythematosus, rheumatoid arthritis, and psoriasis, has since been elucidated in research. Herein, we discuss the mechanistic role of neutrophils, including NETs, in the pathogenesis of systemic juvenile idiopathic arthritis (SJIA) and adult-onset Still’s disease (AOSD), and provide their clinical values as biomarkers for monitoring and prognosis.

Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by dry mouth and dry eyes, with lymphocytic infiltration of the exocrine glands. Saliva is becoming a useful tool to determine the clinical and pathological characteristics of SS because the collection method is easy and non-invasive. Since 1900, salivary proteomic analysis has been performed continuously using a variety of optimized analytical methods. Many studies have identified distinct characteristics of salivary proteins in patients with primary SS, and the changes were related to chronic inflammation and overproduction of immunoglobulins or downregulated secretory function. Several proteomic studies using whole or parotid saliva have evaluated whether several salivary proteins can be used to discriminate SS, including salivary β2-microglobulin, calprotectin, carbonic anhydrase VI, neutrophil gelatinase-associated lipocalin, sialic acid-binding immunoglobulin-like lectin-5, and tripartite motif-containing protein 29. In addition, salivary proinflammatory cytokine levels have been reported to be increased in patients with SS. Although these candidate salivary proteins have exhibited considerable differences in patients with SS, more data are needed to confirm their role as biomarkers. Moreover, the identification of salivary characteristics that can accurately reflect disease activity, predict treatment response and prognosis, and diagnose SS is anticipated.

Unlike other biologic agents for rheumatoid arthritis (RA) that are administered at regular intervals even without flare, rituximab can be administered according to the timing of retreatment determined by the physician. Recently, there has been a tendency to prefer on-demand administration for disease flares rather than regular retreatment. We aimed to investigate the retreatment patterns of rituximab in patients with RA and to identify factors associated with extension of the time interval between retreatment courses. This study included RA patients on rituximab treatment who were enrolled in the Korean Rheumatology Biologics registry (KOBIO) or treated at Ajou University Hospital. Previous or current concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), corticosteroids, number of previous biologic agents, withdrawal, and time intervals of rituximab retreatment were collected. In case of treatment failure, the reasons such as lack of efficacy, adverse events, and others, were also identified. A total of 82 patients were enrolled. The mean follow-up period from the first cycle of rituximab was 46.1 months, and the mean interval between the retreatment courses was 16.3 months. The persistent rates of rituximab after 5 years was 72.4%. Concomitant use of at least two csDMARDs (β = 4.672; 95% CI: 0.089–9.255, p = 0.046) and concomitant use of corticosteroids (β = 7.602; 95% CI: 0.924–14.28, p = 0.026) were independent factors for extending the time interval between the retreatment courses. In conclusion, RA patients treated with rituximab in Korea show high persistence rates. Concomitant use of two or more csDMARDs and concomitant use of corticosteroids with rituximab are associating factors of extending the retreatment time interval. These findings should be considered when selecting rituximab as a treatment for patients with RA.

Muscular dysfunction in rheumatoid arthritis (RA) can affect the quality of life and comorbidities. We enrolled 320 patients with RA, and evaluated their muscle mass, grip strength, and physical performance. Seven (2.2%) and 21 RA patients (6.6%) had sarcopenia, as defined by the European and Asian Working Group for Sarcopenia (EWGS and AWGS), respectively, 54 patients (16.9%) were determined to have low muscle mass with normal muscle function, as defined by the EWGS, 38 patients (11.9%) reported sarcopenia by SARC-F questionnaire. Male sex (odds ratio (OR) 140.65), low body mass index (BMI) (OR 0.41), and use of tumor necrosis factor (TNF) inhibitors (OR 4.84) were associated with a low muscle mass as defined by the EWGS, while male sex, old age, and low BMI were associated with sarcopenia as defined by the AWGS. Old age (OR 1.11), high BMI (OR 1.13), and a high Disease Activity Score 28 (OR 1.95) were associated with sarcopenia as reported on the SARC-F. Male, low BMI, and use of TNF inhibitors were associated with a low muscle mass, while male sex, old age, and low BMI were associated with sarcopenia in patients with long-standing RA.

Infection occurs frequently in patients with systemic lupus erythematosus (SLE), and has been a major cause of morbidity and mortality. However, no large-scale comprehensive studies have estimated the effect of clinical characteristics on serious infection in actual clinical practice yet. We investigated the influence of clinical characteristics on serious infections using electronic medical records data. We conducted a nested case-control study. Patients with SLE who developed serious infection which needs hospitalization or intravenous antibiotics (n = 120) were matched to controls (n = 240) who didn’t. Odds ratios (OR) and 95% confidence intervals (CIs) for infection associated with clinical features were obtained by conditional logistic regression analyses. The conditional logistic regression analysis with adjustment showed that serositis (OR, 2.76; 95% CI, 1.33–5.74), hematologic involvement (OR, 2.53; 95% CI, 1.32–4.87), and use of higher than the low dose of glucocorticoids (GCs; >7.5 mg/d prednisolone-equivalent) (OR, 2.65; 95% CI, 1.31–5.34) were related to serious infections in SLE. Serositis, hematologic involvement, and use of higher than the low dose of GCs were associated with serious infections in patients with SLE.

Relatively little is known about what motivates or prevents patients with rheumatoid arthritis (RA) from adopting physically active lifestyles. This study aimed to evaluate the levels of physical activity and to identify the factors affecting a physically active lifestyle among Korean patients with RA. In this cross-sectional study, data were collected from a rheumatology outpatient clinic of a university-affiliated hospital in South Korea. The levels of physical activity were self-reported using the International Physical Activity Questionnaire. Participants who engaged in more than 600 metabolic equivalent task-minutes/week of physical activity and moderate activity or walking at least three times per week were considered physically active in this study. Structured questionnaires were used to assess perceived barriers and self-efficacy for exercise. Of 345 patients with RA included in this study, about 22% of patients were classified as physically active. Factors associated with a physically active lifestyle were good physical function (odds ratio [OR] = 0.56; 95% confidence interval [CI]: 0.36-0.87) and high levels of exercise self-efficacy (OR = 1.36; 95% CI: 1.20-1.54). Common barriers identified were fatigue, interference with other responsibilities, and a lack of time. Participants showed the lowest self-efficacy for exercise when they had pain and were busy with other activities. The level of physical function and exercise self-efficacy were predictors of physical activity. Individualized physical activity programs tailored to personal abilities and barriers and increasing exercise self-efficacy are needed to facilitate engagement of physical activity in Korean patients with RA. KEY POINTS: • Factors associated with a physically active lifestyle were good physical function and high levels of exercise self-efficacy. • The levels of exercise self-efficacy in Korean patients with RA are low compared to those in other populations. • Frequently encountered barriers in the subjects were being too tired, interference with other responsibilities, and lack of time. • Individualized physical activity programs tailored to personal abilities and barriers and increasing exercise self-efficacy are needed to facilitate engagement of physical activity in Korean patients with RA.

Objectives: This study aimed to provide reliable information on the impact of low-dose glucocorticoids (GCs) on the bone mineral density (BMD) of patients with rheumatoid arthritis (RA). Methods: This retrospective study enrolled 933 patients with RA who continued the consumption of GCs (GC group) and 100 patients who had discontinued consumption for &gt, 1 year (no-GC group). The BMD values were measured at baseline and follow-up, and the annual rate of change in BMD between the groups was compared using dual-energy X-ray absorptiometry. We used multiple linear regression analysis to identify the factors associated with changes in BMD. Results: The demographic characteristics and use of medical treatments affecting bone metabolism were similar between the two groups. Furthermore, there were no significant differences in the annual rate of changes in BMD and incidence of newly developed osteoporosis and incidental fractures between the two groups. Multiple linear regression analysis revealed that the disease activity score for 28 joints with erythrocyte sedimentation rate was the only factor affecting the annual rate of changes in BMD, and it was inversely proportional to changes in BMD. Conclusion: The benefits of GC therapy in attenuating inflammation compensate for the risk of osteoporosis if adequate measures to prevent bone loss are implemented in patients with RA.

Studies that investigate the association between toll-like receptor (TLR)-4 or TLR9 gene polymorphisms and remission from the disease in RA patients taking tumor necrosis factor alpha (TNF-α) inhibitors have yet to be conducted. In this context, this study was designed to investigate the effects of polymorphisms in TLR4 and TLR9 on response to TNF-α inhibitor and develop various machine learning approaches to predict remission. A total of six single nucleotide polymorphisms (SNPs) were investigated. Logistic regression analysis was used to investigate the association between genetic polymorphisms and response to treatment. Various machine learning methods were utilized for prediction of remission. After adjusting for covariates, the rate of remission of T-allele carriers of TLR9 rs352139 was about 5 times that of the CC-genotype carriers (95% confidence interval (CI) 1.325–19.231, p = 0.018). Among machine learning algorithms, multivariate logistic regression and elastic net showed the best prediction with the AUROC value of 0.71 (95% CI 0.597 - 0.823 for both models). This study showed an association between a TLR9 polymorphism (rs352139) and treatment response in RA patients receiving TNF-α inhibitors. Moreover, this study developed various machine learning methods for prediction, among which the elastic net provided the best model for remission prediction.

We aimed to characterize the salivary protein components and identify biomarkers in patients with systemic lupus erythematosus (SLE). A proteomic analysis using two-dimensional gel electrophoresis and mass spectrometry was performed to determine the alterations of salivary proteins between patients with SLE and healthy controls, and the concentrations of the candidate proteins were measured through Western blot analysis and the enzyme-linked immunosorbent assay. The 10 differentially expressed protein spots were immunoglobulin gamma-3 chain C region (IGHG3), immunoglobulin alpha-1 chain C region, protein S100A8, lactoferrin, leukemia-associated protein 7, and 8-oxoguanine DNA glycosylase. The patients with SLE exhibited enhanced salivary IGHG3 (3.9 ± 2.15 pg/mL) and lactoferrin (4.7 ± 1.8 pg/mL) levels compared to patients with rheumatoid arthritis (1.8 ± 1.01 pg/mL and 3.2 ± 1.6 pg/mL, respectively, p &lt, 0.001 for both) or healthy controls (2.2 ± 1.64 pg/mL and 2.2 ± 1.7 pg/mL, respectively, 0.001 for both). The salivary IGHG3 levels correlated with the erythrocyte sedimentation rate (r = 0.26, p = 0.01), anti-double-stranded DNA (dsDNA) antibody levels (r = 0.25, p = 0.01), and nephritis (r = 0.28, p = 0.01). The proteomic analysis revealed that the salivary IGHG3 levels were associated with SLE and lupus disease activity, suggesting that salivary IGHG3 may be a promising noninvasive biomarker for SLE.

Systemic juvenile idiopathic arthritis (JIA) and adult-onset Still's disease (AOSD) are systemic inflammatory disorders that manifest as high-spiking fever, joint pain, evanescent skin rash, and organomegaly. Their pathogenesis is unclear, but inflammation is triggered by activation of the innate immune system with aberrant production of proinflammatory cytokines. Along with extrinsic factors, intrinsic pathways can trigger an unexpected immune response. Damage-associated molecular patterns (DAMPs) induce the activation of innate immune cells, leading to sterile inflammation in systemic JIA and AOSD. These endogenous proteins interact with Toll-like receptors (TLRs), which are pattern recognition receptors, and mediate immune signaling following stimulation by pathogen-associated molecular patterns and DAMPs. Several DAMPs, such as S100 proteins, play a role in the development or severity of systemic JIA and AOSD, in which their interactions with TLRs are altered. Also, the expression levels of genes encoding DAMPs contribute to the susceptibility to systemic JIA and AOSD. Herein, we review reports that TLR and DAMP signaling initiates and/or maintains the inflammatory response in systemic JIA and AOSD, and their correlations with the clinical characteristics of those diseases. In addition, we assess their utility as biomarkers or therapeutics for systemic JIA and AOSD.

ObjectiveThis study aimed to examine the frequency and risk factors of complications during pregnancy in women with systemic lupus erythematosus (SLE).MethodsThe medical records of patients with SLE and age-matched controls at Ajou University Hospital were collected. Clinical features and pregnancy complications in women with SLE were compared to those of the controls. Multivariate logistic regression analysis was performed to determine the predictors of adverse maternal and fetal outcomes.ResultsWe analyzed 163 pregnancies in patients with SLE and 596 pregnancies in the general population; no significant differences regarding demographic characteristics were noted. Patients with SLE experienced a higher rate of stillbirth (OR 13.2), preeclampsia (OR 4.3), preterm delivery (OR 2.8), intrauterine growth retardation (OR 2.5), admission to neonatal intensive care unit (OR 2.2), and emergency cesarean section (OR 1.9) than the control group. Multivariate regression analysis revealed that thrombocytopenia, low complement, high proteinuria, high SLE Disease Activity Index (SLEDAI), low Lupus Low Disease Activity State (LLDAS) achievement rate, and high corticosteroid (CS) dose were associated with adverse pregnancy outcomes. In the receiver-operating characteristic curve analysis, the optimal cutoff value for the cumulative and mean CS doses were 3500 mg and 6 mg, respectively.ConclusionPregnant women with SLE have a higher risk of adverse pregnancy outcomes. Pregnancies are recommended to be delayed until achieving LLDAS and should be closely monitored with the lowest possible dose of CS.

The use of biological agents in patients with rheumatic diseases has achieved the therapeutic target, i.e., remission or low disease activity. The share of biological agents has been growing with the approval of biosimilars, which have been recognized for their equivalent efficacy, safety, pharmacokinetics, and immunogenicity to the original as well as their reduced economic burden.Biosimilars are being examined for their bioequivalence to reference products in randomized-controlled trials; however, the use of biosimilars in actual clinical practice is complicated owing to issues with switching and comorbidities. Therefore, this review describes real-world data in the rapidly evolving field of biosimilars in the treatment of rheumatoid arthritis and spondyloarthropathy, including ankylosing spondylitis and psoriatic arthritis.According to published data, the use of biosimilars for inflammatory arthritis led to no significant inferiority in treatment outcomes and resulted in considerable cost savings in the real-world. Currently, beyond the use of biosimilars, issues with the interchangeability of biosimilars, including immunogenicity, should be addressed. Strategies to overcome these concerns will improve treatment efficacy and safety in patients with inflammatory arthritis.

Background We purposed to evaluate the seasonality and associated factors of the incidence of gout attacks in Korea. Methods We prospectively enrolled patients with gout attacks who were treated at nine rheumatology clinics between January 2015 and July 2018 and followed them for 1-year. Demographic data, clinical and laboratory features, and meteorological data including seasonality were collected. Results Two hundred-five patients (men, 94.1%) were enrolled. The proportion of patients with initial gout attacks was 46.8% (n = 96). The median age, body mass index, attack duration, and serum uric acid level at enrollment were 50.0 years, 25.4, 5.0 days, and 7.4 mg/dL, respectively. Gout attacks were most common during spring (43.4%, P < 0.001) and in March (23.4%, P < 0.001). A similar pattern of seasonality was observed in the group with initial gout attacks. Alcohol was the most common provoking factor (39.0%), particularly during summer (50.0%). The median diurnal temperature change on the day of the attack was highest in the spring (9.8°C), followed by winter (9.3°C), fall (8.6°C), and summer (7.1°C) (P = 0.027). The median change in humidity between the 2 consecutive days (the day before and the day of the attack) was significantly different among the seasons (3.0%, spring; 0.3%, summer; −0.9%, fall; −1.2%, winter; P = 0.015). One hundred twenty-five (61%) patients completed 1-year follow-up (51% in the initial attack group). During the follow-up period, 64 gout flares developed (21 in the initial attack group). No significant seasonal variation in the follow-up flares was found. Conclusion In this prospective study, the most common season and month of gout attacks in Korea are spring and March, respectively. Alcohol is the most common provoking factor, particularly during summer. Diurnal temperature changes on the day of the attack and humidity changes from the day before the attack to the day of the attack are associated with gout attack in our cohort., Graphical Abstract

Background Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies. We aimed to find salivary protein biomarkers in Korean patients with SLE. Methods The salivary proteins were subjected to 2-dimensional gel electrophoresis (2-DE). The spots exhibiting >2-fold intensity change between SLE and healthy subjects (HSs) were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) analysis. The amounts of candidate proteins in saliva of patients with SLE and rheumatoid arthritis (RA), and HSs were analyzed using western blotting and enzyme-linked immunosorbent assay. Results The proteomic analysis using 2-DE and MS revealed 10 differentially expressed protein spots, which included immunoglobulin gamma-3 chain C (IGHG3), protein S100, lactoferrin, leukemia-associated protein 7, and 8-oxoguanine DNA glycosylase. The patients with SLE exhibited enhanced salivary IGHG3 (3.9 ± 2.15 pg/mL) and lactoferrin (4.7 ± 1.8 pg/mL) levels than patients with rheumatoid arthritis (RA) (1.8 ± 1.01 pg/mL and 3.2 ± 1.6 pg/mL, respectively, p Conclusions The levels of salivary IGHG3 and lactoferrin were higher in patients with SLE. In addition, salivary IGHG3 levels correlated with SLE disease activity markers. Acknowledgements This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI16C0992).

Background: Despite the improvement from the introduction of tumor necrosis factor inhibitors (TNFi) in the rheumatoid arthritis (RA), TNFi therapy fails for more than 30% or results in a partial response. Thus, we aimed to explore treatment marker by examining the association of single nucleotide polymorphisms (SNPs) with response to TNFi therapy.Method: Genes associated with RA or RA treatment were reviewed and fourteen SNPs with minor allele frequency ≥ 20% in the East Asian populations were selected and analyzed. Data were collected from 105 RA patients. Our primary endpoint was the disease activity score using 28-joint count after six months of treatment (DAS28-6month). The secondary outcomes were the subcomponents of DAS28.Results: A total of 88 patients were included in the final analyses. Among the 14 SNPs analyzed, one SNP showed statistical significance in DAS28-6month: patients with the GG allele of RETN rs1862513 had a 4.7 times higher chance of low disease activity at 6-months than GC or CC-carriers (p = 0.033), as indicated by multivariable logistic regression analysis. Rs3397 was marginally significant in univariate analysis (p=0.059), but was significant in the multivariable model (p=0.041). The final model explained 24.5% (Nagelkerke R2) of the variance in DAS28-6month.Conclusion: Our results demonstrated that, among the genes related to RA, SNPs in RETN and TNFRSF1B were associated with the response of TNFi treatment.

INTRODUCTION Secondary amyloidosis is a rare complication of rheumatoid arthritis (RA) that is histologically characterized by the deposition of amyloid fibrils in target organs, such as the kidneys and gastrointestinal tract. Controlling the inflammatory response is essential to prevent organ dysfunction in amyloid A (AA) amyloidosis secondary to RA, and no clear treatment strategy exists. PATIENT CONCERNS AND DIAGNOSIS A 66-year-old woman with RA, who had been treated with disease-modifying anti-rheumatic drugs for 1 year, presented with recurrent abdominal pain and prolonged diarrhea. Endoscopy showed chronic inflammation, and colon tissue histology confirmed AA amyloidosis. INTERVENTIONS AND OUTCOMES After tocilizumab therapy was begun, her diarrhea and abdominal pain subsided, and articular symptoms improved. Biologic drugs for RA have been used in patients with secondary AA amyloidosis, including tumor necrosis factor and Janus kinase inhibitors, interleukin 6 blockers, and a T cell modulator. Here, we systematically review existing case reports and compare the outcomes of RA-related AA amyloidosis after treatment with various drugs. CONCLUSION The data indicate that biologic drugs like tocilizumab might be treatments of choice for AA amyloidosis secondary to RA.

Osteoporosis is a common adverse event among patients on glucocorticoid therapy. Glucocorticoids reduce bone formation and increase cortical porosity in proportion to the dose and duration of glucocorticoid use. While the epidemiology of glucocorticoid-induced osteoporosis has been well characterized, its pathophysiology and effective management remain unclear. Several recommendations for glucocorticoid-induced osteoporosis are used to determine which patients on long-term glucocorticoid treatment to treat and when. The fracture risk can be assessed using dual-energy X-ray absorptiometry and the Fracture Risk Assessment Tool algorithm, along with other clinical factors. The management of glucocorticoid-induced osteoporosis includes anti-osteoporotic therapy and measures to prevent bone loss. Bisphosphonates are currently the first choice treatment, with teriparatide and denosumab being alternatives. (Korean J Med 2017;92:142-149)

It has been reported Human Leukocyte Antigen (HLA) gene polymorphism is a risk factor for the development of Beh&ccedil, et&rsquo, s disease (BD). In this study, the association of HLA class II subtypes HLA-DP, DQ, DR, and T cell subsets in BD patients with arthritis was evaluated. Frequencies of HLA-DP, DQ, DR positive cells, and T cell subsets in peripheral blood leukocytes (PBL) were measured by flow cytometric analysis in BD, and compared to rheumatoid arthritis as disease controls and healthy controls. Frequencies of HLA-DQ were significantly decreased in whole PBL and granulocytes of BD active patients as compared to healthy controls. In monocytes populations, proportions of HLA-DR positive cells were significantly increased in BD active patients as compared to healthy controls. Proportions of CD4+CCR7+ and CD8+CCR7+ cells were significantly higher in BD active patients than in BD inactive in whole PBL. Frequencies of CD4+CD62L- and CD8+CD62L- cells in lymphocytes were significantly decreased in active BD than those in inactive BD. There were also correlations between disease activity markers and T cell subsets. Our results revealed HLA-DP, DQ, and DR expressing cell frequencies and several T cell subsets were significantly correlated with BD arthritis symptoms.

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by long-standing inflammation in multiple joints. Rituximab, a monoclonal antibody, which binds to CD20, is e...

Background The neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and monocyte‐to‐lymphocyte ratio (MLR) are indicators of systemic inflammation and are useful as markers in systemic rheumatic diseases. In this study, we compared the NLR, PLR, and MLR among patients with polymyalgia rheumatica (PMR) and rheumatoid arthritis (RA), and explored possible associations with clinical features, disease activity, and prognosis in patients with PMR. Methods The study enrolled 94 patients with PMR and 242 patients with RA who were initially diagnosed at the rheumatology clinic of a university‐based tertiary hospital. Symptoms, physical examination, and medical histories were collected with the results of laboratory tests. Results Neutrophil‐to‐lymphocyte ratio (4.5 ± 3.3 vs 2.8 ± 1.8), PLR (222.7 ± 115.5 vs 159.7 ± 78.1), and MLR (0.4 ± 0.3 vs 0.3 ± 0.2) were higher in patients with PMR compared with patients with RA (all P

Background: Polymyalgia rheumatica (PMR) is a systemic inflammatory disorder, which develops inflammatory pain and stiffness of large joints. There is no specific serological marker or test to differentiate PMR. Objectives: In this study, we compared the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) among patients with polymyalgia rheumatica (PMR) and rheumatoid arthritis (RA), and explored possible associations with clinical features, disease activity, and prognosis in PMR. Methods: A total of 94 PMR and 242 RA patients who were initially diagnosed at the rheumatology clinic of a university-based tertiary hospital were enrolled. Symptoms, physical examination, and medical histories were collected with the results of laboratory tests. Results: NLR (4.5 ± 3.3 vs. 2.8 ± 1.8), PLR (222.7 ± 115.5 vs. 159.7 ± 78.1), and MLR (0.4 ± 0.3 vs. 0.3 ± 0.2) were higher in patients with PMR compared with patients with RA (all p Conclusion: This study found that NLR, PLR, and MLR in patients with PMR were higher than in those with RA. Furthermore, NLR, PLR, and MLR levels were associated with disease activity and specific clinical features, although they could not predict prognosis in patients with PMR. References: [1] van der Geest KS, Abdulahad WH, Rutgers A, Horst G, Bijzet J, Arends S, et al. Serum markers associated with disease activity in giant cell arteritis and polymyalgia rheumatica. Rheumatology (Oxford). 2015;54(8):1397-402. [2] Erre GL, Paliogiannis P, Castagna F, Mangoni AA, Carru C, Passiu G, et al. Meta-analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio in rheumatoid arthritis. Eur J Clin Invest. 2018:e13037 Disclosure of Interests: Ju-Yang Jung: None declared, Jiwon Kim: None declared, Chang-Hee Suh Consultant for: Celltrion, Inc, Hyoun-Ah Kim: None declared

Background Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by pathogenic autoantibodies and uncontrolled inflammatory response. There are few reliable biomarkers available for diagnosis and monitoring the disease. Objectives We tried to find and characterize specific protein components in saliva of patients with SLE for their use as biomarkers in future. Methods Salivary proteins were prepared from 11 samples from patients with SLE and healthy controls (HC), and were subjected to 2-dimensional gel electrophoresis (2-DE). The spots with greater than 2 fold change in intensity were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MS) analysis. The relative and absolute amounts of the several candidate proteins in saliva of patients with SLE and rheumatoid arthritis (RA), and HC were analyzed using western blotting, and enzyme-linked immunosorbent assay. Results Proteomic analysis using 2-DE and MS identified 20 differentially expressed protein spots in the saliva of SLE patients compared in that of HC. Among them, proteins with more than two-fold differences in expression were found as immunoglobulin gamma-3 chain C (IGHG3), immunoglobulin alpha-1 chain C region, protein S100, lactotransferrin, leukemia-associated protein 7, and 8-oxoguanine DNA glycosylase (OGG1). salivary IGHG3 levels were increased in SLE (3.9 ± 2.2 pg/mL) compared to those in RA (1.8 ± 1.0 pg/mL, p Conclusion Salivary IGHG3 and lactotransferrin levels were significantly increased in patients with SLE compared to those in patients with RA or HC, and could be used as potential biomarkers of SLE. References [1] Baldini C, Giusti L, Ciregia F, Da Valle Y, Giacomelli C, Donadio E, Sernissi F, Bazzichi L, Giannaccini G, Bombardieri S, Lucacchini A: Proteomic analysis of saliva: a unique tool to distinguish primary Sjogren’s syndrome from secondary Sjogren’s syndrome and other sicca syndromes. Arthritis Res Ther 13: R194, 2011 [2] Lamy E, Mau M: Saliva proteomics as an emerging, non-invasive tool to study livestock physiology, nutrition and diseases. J Proteomics 75: 4251-4258, 2012 Disclosure of Interests Ju-Yang Jung: None declared, Jiwon Kim: None declared, Hyoun-Ah Kim: None declared, Chang-Hee Suh Consultant for: Celltrion, Inc

Background: To compare the frequency of high-risk osteoporotic fracture in patients with knee OA (OA) using the fracture risk assessment tool (FRAX) and the bone mineral density (BMD). Methods: We retrospectively assessed 282 Korean patients with knee OA who visited five medical centers and 1165 healthy controls (HCs) aged &ge, 50 years without knee OA. After matching for age, sex, and body mass index, 478 subjects (239 patients with knee OA and 239 HCs) were included. Results: Based on the BMD, the frequency of osteoporosis was 40.2% in patients with knee OA and 36.4% in HCs. The predicted mean FRAX major osteoporotic fracture probabilities calculated with or without femur neck BMD differed significantly between the knee OA and HCs (6.9 &plusmn, 3.8% versus 6.1 &plusmn, 2.8%, p = 0.000 and 8 &plusmn, 3.6% versus 6.8 &plusmn, 2.3%, p &lt, 0.001, respectively). The mean FRAX hip fracture probabilities calculated with or without femur neck BMD differed significantly in the knee OA and HCs (2.1 &plusmn, 2.4% versus 1.7 &plusmn, 1.8%, p = 0.006 and 3 &plusmn, 2.3% versus 2.4 &plusmn, 1.6%, p &lt, 0.001, respectively). Conclusion: Our study suggests that FRAX may have a clinical impact on treatment decisions to reduce osteoporotic facture in patients with knee OA.

Background: Reduced bone mass or osteoporotic fracture are one of major complications in chronic inflammatory diseases including systemic lupus erythematosus (SLE). Fracture risk was found to be determined not only by conventional factors such as age and a lack of physical activity, but also by systemic inflammation, musculoskeletal symptoms, and administration of glucocorticoids. Objectives: We evaluated the prevalence of osteoporosis and fracture risk in patients with systemic lupus erythematosus (SLE), and compared the fracture risk assessment tool (FRAX) criteria and bone mineral density (BMD) criteria established by the World Health Organization (WHO). Methods: Data of 182 female patients with SLE were collected retrospectively in 5 hospitals between January 2012 and December 2016. The FRAX criteria for high-risk osteoporotic fractures were calculated including and excluding the scores in BMD, respectively. The high risk for fracture by FRAX criteria and BMD criteria by WHO was defined as 10-year probability of ≥ 20% for major osteoporotic fracture or ≥ 3% for hip fracture, and T score ≤ −2.5 or Z score ≤ −2.0, respectively. Results: The mean age was 51.1 ± 11.23 years, 114 (62.3%) were postmenopausal. Osteoporotic fractures were detected in 9 (4.9%) among the 127 patients taking T-L spine X-ray. The numbers of candidates for pharmacological intervention using the FRAX criteria with and without BMD and the WHO criteria were 26 (14.2%), 23 (12.6%), and 51 (27.9%), respectively. Only 50–69.6% of the patients in the high-risk group using the FRAX criteria and the WHO criteria were receiving osteoporosis treatments. The following were associated with candidates for pharmacological intervention for fracture using the FRAX criteria without BMD and WHO criteria: Age (OR 1.422, 95% CI 1.22–1.659 and OR 1.157, 95% CI 1.083–1.236), and weight (OR 0.87, 95% CI 0.798–0.949 and OR 0.943, 95% CI 0.901–0.986), respectively. In addition, cumulative glucocorticoids dose (OR 1.073, 95% CI 1.024–1.123) was associated with candidates for pharmacological intervention for fracture using the FRAX criteria with BMD. Conclusion: The proportion of SLE patients with a high risk of osteoporotic fractures by the FRAX criteria with and without BMD and the WHO criteria was 12.6%–27.9%. Among the candidate patients, only 50%–69.6% were taking osteoporotic medications. Independent risk factors for osteoporotic fractures in SLE patients were older age, lower weight and cumulative glucocorticoids dose. References: [1] Cramarossa G, Urowitz MB, Su J, Gladman D, Touma Z. Prevalence and associated factors of low bone mass in adults with systemic lupus erythematosus. Lupus. 2017;26:365-372. [2] Barbulescu A, Vreju FA, Criveanu C, Rosu A, Ciurea P. Osteoporosis in Systemic Lupus Erythematosus - Correlations with Disease Activity and Organ Damage. Curr Health Sci J. 2015;41:109-114 Disclosure of Interests: Jiwon Kim: None declared, Ju-Yang Jung: None declared, Hyoun-Ah Kim: None declared, Chang-Hee Suh Consultant for: Celltrion, Inc

Background Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by impaired clearance of apoptotic cells. Milk fat globule epidermal growth factor8 (MFG-E8) is a protein connects between v3 integrin of phagocytic macrophage and phosphatidylserine of apoptotic cell surface. In this study, we determine whether genetic variation of MFG-E8 gene and serum protein concentration are associated with SLE. Methods Single nucleotide polymorphisms (SNPs) were genotyped by three steps. At first, we used polymerase chain reaction in 20 patients with SLE and 20 normal controls (NC) for sequencing of a whole MFG-E8 gene in Korean population. Then we screened 12 selected SNPs in 55 SLE and 30 NC. Finally, we used Taq-man probe assay in 225 SLE and 230 NC for genotyping of targeted 5 SNPs. Furthermore, serum MFG-E8 concentrations were analysed in SLE. Results SLE patient‘s mean age was 35.7±7.8 years and 92% were women, which is not different form NC. rs2271715’s C allele and rs3743388’s G allele were shown higher frequency in SLE than NC (p=0.036, p=0.005, respectively). As the linkage disequilibrium test, rs1878326 and rs1878327 were shown high linkage (r2=0.879). Three haplotypes were found by four SNPs (rs4945, rs1878327, rs2271715, and rs3743388); AACG, CGCG, and CGTC. The CGCG haplotype was significantly higher in patients with SLE compared with NC (p=0.001, odds ratio=2.31). rs4945 was associated with erythrocyte sedimentation rate and rs1878327 was associated with alopecia, C-reactive protein, complement 3, anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibody, and systemic lupus erythematosus disease activity score. rs2271715 and rs3743388 were associated with renal disease, cumulated steroid dose, cyclophosphamide and mycophenolate mofetil usage and rs3743388 also was associated with anti-dsDNA antibody. Serum MFG-E8 concentration was shown significantly higher in SLE than NC (2,030.3±1,292.3 pg/mL vs 1,433.0±946.3 pg/mL, p=0.017). Conclusions Our data suggest possibility that MFG-E8 rs2271715 and rs3743388 SNP can be involved in susceptibility of SLE. Also, these SNPs are associated with renal disease and disease activity in SLE. Furthermore, rs4945 and rs1878327 polymorphisms may be a marker of disease activity. Funding Source(s): This research was supported by a grant of the Korea Health Technology R and D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI16C0992).

Background Infection occurs frequently in patients with systemic lupus erythematosus (SLE) and has been a major cause of morbidity and mortality. However, no large-scale comprehensive studies have estimated the effect of clinical characteristics on serious infections in actual clinical practice yet. We investigated the influence of clinical characteristics on serious infections using electronic medical record data. Methods We conducted a nested case-control study. Patients with SLE who developed serious infections needing hospitalization or intravenous antibiotic administration were matched to controls who did not. Odds ratios (ORs) and 95% confidence intervals (CIs) for infection associated with the clinical characteristics were obtained using logistic regression analyses. Results Among the total of 120 cases with infection, 93 (77.5%) were bacterial infections with 40 (25%) upper respiratory tract infections, 26 (21.7%) pneumonia, 24 (20%) sepsis, and 22 (18.3%) urinary tract infections. The patients with serious infections had lower hemoglobin and C3 levels and less frequent hydroxychloroquine administration. In addition, they had more frequent nephritis, serositis, and hematologic involvement and took higher than the low dose of glucocorticoids (GCs;>7.5 mg/d prednisolone-equivalent). The conditional logistic regression analysis with adjustment showed that serositis (OR, 2.76; 95% CI, 1.33–5.74), hematologic involvement (OR, 2.53; 95% CI, 1.32–4.87), and use of higher than the low dose of GCs (OR, 2.65; 95% CI, 1.31–5.34) were related to serious infections in SLE Conclusions Serositis, hematologic involvement, and use of higher than the low dose of GCs are risk factors for serious infections in patients with SLE. Funding Source(s): This research was supported by a grant from the Korea Health Technology R and D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI16C0992).

Background Multifocal osteonecrosis (ON) is defined as ON involving three or more distinct anatomical sites. We investigated the clinical characteristics and utility of whole-body bone scans (WBBS) in patients with multifocal ON. Methods A total of 254 patients with ON confirmed by magnetic resonance imaging (MRI) or X-rays of the hips or other anatomic regions were evaluated using WBBS and divided into those with multifocal disease and those with oligofocal disease; their clinical characteristics were then compared. All data were analyzed retrospectively both visually and quantitatively (via uptake grading and defect scoring). Associations between the MRI Association Research Circulation Osseous (ARCO) classification and bone scan photon defects and uptake grade were assessed. Factors associated with multifocal ON were identified using logistic regression. Results Of the 254 ON patients, 26 (10.2%) had multifocal ON. Their mean age (42.8 ± 14.3 years) was less than that of patients with oligofocal ON (50.9 ± 15.4 years; p = 0.011). Comorbidities, corticosteroid use, and treatment with immunosuppressive agents were more frequent in patients with multifocal ON. Age (odds ratio [OR] = 0.964, p = 0.013), the presence of a comorbidity (OR = 3.387, p = 0.006), present corticosteroid use (OR = 5.696, p

(1) Background: We evaluated the prevalence and fracture risk of osteoporosis in patients with rheumatoid arthritis (RA), and compared the fracture risk assessment tool (FRAX) criteria and bone mineral density (BMD) criteria established by the World Health Organization (WHO). (2) Methods: This retrospective cross-sectional study, which included 479 RA patients in 5 hospitals, was conducted between January 2012 and December 2016. The FRAX criteria for high-risk osteoporotic fractures were calculated including and excluding the BMD values, respectively. The definition of high risk for fracture by FRAX criteria and BMD criteria by WHO was 10-year probability of &ge, 20% for major osteoporotic fracture or &ge, 3% for hip fracture, and T score &le, &minus, 2.5 or Z score &le, 2.0, respectively. (3) Results: The mean age was 61.7 &plusmn, 11.9 years. The study included 426 female patients (88.9%), 353 (82.9%) of whom were postmenopausal. Osteoporotic fractures were detected in 81 (16.9%) patients. The numbers of candidates for pharmacological intervention using the FRAX criteria with and without BMD and the WHO criteria were 226 (47.2%), 292 (61%), and 160 (33.4%), respectively. Only 69.2%&ndash, 77% of the patients in the high-risk group using the FRAX criteria were receiving osteoporosis treatments. The following were significant using the WHO criteria: female (OR 3.55, 95% CI 1.46&ndash, 8.63), age (OR 1.1, 95% CI 1.08&ndash, 1.13), and BMI (OR 0.8, 95% CI 0.75&ndash, 0.87). Glucocorticoid dose (OR 1.09, 95% CI 1.01&ndash, 1.17), age (OR 1.09, 95% CI 1.06&ndash, 1.12), and disease duration (OR 1.01, 95% CI 1&ndash, 1.01) were independent risk factors for fracture. (4) Conclusions: The proportion of RA patients with a high risk of osteoporotic fractures was 33.4%&ndash, 61%. Only 69.2%&ndash, 77% of candidate patients were receiving osteoporotic treatments while applying FRAX criteria. Independent risk factors for osteoporotic fractures in RA patients were age, the dose of glucocorticoid, and disease duration.

Gout is a chronic disease associated with deposition of monosodium urate crystals and accompanied by diabetes, hypertension, and dyslipidemia. Hypertriglyceridemia is common among patients with gout, and fenofibrate is usually used to reduce triglyceride levels. The aim of this study is to determine the effect of uric acid reduction by fenofibrate in patients with gout administered uric acid lowering agents (viz., the xanthine oxidase inhibitors allopurinol and febuxostat). Data from 863 patients with gout were collected from electronic medical records comprising information on underlying diseases, laboratory findings, and drug histories. Among all the patients, 70 (8.11%) took fenofibrate with allopurinol or febuxostat. Male and young patients took fenofibrate more frequently, and hypertension was less frequent in patients administered xanthine oxidase inhibitors and fenofibrate than in those administered only xanthine oxidase inhibitors. After the treatment, serum uric acid levels more significantly decreased (−1.81 ± 2.41 vs. −2.40 ± 2.28 mg/dL, p = 0.043) in patients with fenofibrate cotreatment, than in those administered allopurinol or febuxostat alone. The effect of uric acid reduction was larger (b = −1.098, p

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by diverse autoantibodies and varied clinical features. There is much interest in biomarkers, but diagnostic and disease activity markers in actual clinical practice remain complement, autoantibodies including anti-dsDNA antibody, leukocyte count and urinalysis. This article reviews recently studied epigenetic, protein and metabolomic biomarkers. Although there are many studies about the SLE pathogenesis and biomarkers, only some biomarkers have been validated. This is most commonly because there are few prospective longitudinal and interventional studies that validate the biomarker utility. Recently elucidated candidate biomarkers need well-designed prospective studies and standardized assays for commercialization. Moreover, continuous research for SLE pathogenesis can promote biomarker development using new technologies, such as microarrays, proteomics and metabolomics techniques.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with heterogeneous clinical manifestations mediated by immune dysregulation. We aimed to analyze the metabolomic differences in free fatty acids (FFAs) between patients with SLE and healthy controls (HCs). In this study, the levels of 24 FFAs, as their tert-butyldimethylsilyl derivatives, in the plasma of 41 patients with SLE and 41 HCs, were investigated using gas chromatography with mass spectrometry in selected-ion monitoring mode. The results showed that patients with SLE and HCs had significantly different levels of 13 of the 24 FFAs. The levels of myristic, palmitoleic, oleic, and eicosenoic acids were significantly higher, whereas the levels of caproic, caprylic, linoleic, stearic, arachidonic, eicosanoic, behenic, lignoceric, and hexacosanoic acids were significantly lower in patients with SLE, than in the HCs. In the partial-correlation analysis of the FFA profiles and markers of disease activity of SLE, several metabolic markers correlated with SLE disease activity. Our results provide a comprehensive understanding of the relationship between FFAs and markers of SLE disease activity. Thus, this approach has promising potential for the discovery of metabolic biomarkers of SLE.

Objectives This study aims to compare the clinical characteristics of systemic sclerosis (SSc) patients with or without interstitial lung disease (ILD), and figure out whether the differences can be useful to suspect ILD in SSc. Patients and methods We retrospectively collected the clinical data of 108 patients with SSc (13 males, 95 females; mean age 50.1±13.5 years; range 14 to 78 years) and compared them according to the presence of ILD. ILD was confirmed by chest computed tomography, and pulmonary arterial hypertension was suspected when right ventricular systolic pressure was ≥40 mmHg based on echocardiography. Results Of the 108 patients, 49 (45.4) had diffuse type and 59 (54.6) had limited type SSc. Disease duration, percentages of positive anti-scleroderma 70 (anti-Scl70) antibody and anti-centromere antibody, white blood cell, platelet, erythrocyte sedimentation rate (ESR), and presence of pulmonary hypertension differed significantly. On multivariate logistic analysis, positive titer of anti-Scl70 antibody (odds ratio [OR]=15.65, p

Objective.Interleukin 33 (IL-33), a member of the IL-1 family and a ligand of the orphan receptor ST2, plays key roles in innate and adaptive immunity. We examined the associations between IL-33/ST2 levels and clinical manifestations of patients with active adult-onset Still’s disease (AOSD).Methods.Blood samples were collected from 40 patients with active AOSD, 28 patients with rheumatoid arthritis (RA), and 27 healthy controls (HC). The serum levels of IL-33 and soluble ST2 were determined using ELISA. Expression levels of IL-33 and ST2 in biopsy specimens obtained from 34 AOSD patients with rash were immunohistochemically investigated.Results.IL-33 levels of patients with AOSD were higher than those of patients with RA and HC. Soluble ST2 levels of patients with AOSD were higher than those of HC, but not of patients with RA. Serum IL-33 levels correlated with systemic score, erythrocyte sedimentation rate, ferritin levels, and aspartate transaminase levels. However, serum soluble ST2 levels correlated only with ferritin levels. The numbers of inflammatory cells expressing IL-33 and ST2 were elevated in skin lesions of patients with AOSD compared to HC, but did not differ from those of the skin lesions of eczema or psoriasis.Conclusion.We found significantly higher serum IL-33 and soluble ST2 levels in patients with active AOSD. Results indicate that the IL-33/ST2 signaling pathway may play a role in the pathogenesis of the acute inflammation and skin manifestations associated with AOSD.

C-X-C motif chemokine 9 (CXCL9), CXCL10, and CXCL11 are produced in response to interferon-γ (IFN-γ) and trigger inflammation with the accumulation of activated lymphocytes. It appears that these chemokines could play a role in the pathogenesis of adult-onset Still’s disease (AOSD). Therefore, we investigated the associations between the levels of these chemokine and clinical manifestations in patients with active AOSD. Serum levels of IFN-γ, CXCL9, CXCL10 and CXCL11 were determined using enzyme-linked immunosorbent assays. IFN-γ levels were higher in AOSD patients than in rheumatoid arthritis (RA) patients (p = 0.001) or healthy controls (HCs) (p = 0.032). AOSD patients also exhibited higher levels of CXCL9, CXCL10, and CXCL11 compared with RA patients (p p p = 0.012), eczema (p = 0.019), and psoriasis (p = 0.009) groups. Levels of the IFN-γ–induced chemokines, CXCL9, CXCL10 and CXCL11, were elevated and correlated with several disease activity markers. These interferon-γ–induced chemokines may contribute to inflammatory responses and skin manifestations in AOSD.

The neutrophil-to-lymphocyte ratio (NLR) is the proportion of absolute neutrophil count to lymphocytes on routine complete blood count (CBC) tests, and has been studied as a simple marker of the systemic inflammatory response. This study was performed to investigate whether the NLR could be used as a tool to diagnose and predict prognosis in cases of adult-onset Still's disease (AOSD).We retrospectively reviewed 164 patients with suspected AOSD. Among 164 patients with suspected AOSD, 37 patients received another diagnosis (such as viral infection) and were compared with the 127 patients who received a diagnosis of AOSD. Laboratory tests including CBCs, ferritin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and the NLR were evaluated.AOSD patients showed higher neutrophil counts, lower lymphocyte counts, higher NLRs, and higher levels of ferritin, ESR, and CRP than non-AOSD patients (all P < .001). In receiver operating characteristic (ROC) curve analysis of the NLR for diagnosis of AOSD, the area under the curve (AUC) was highest at 0.967 (95% CI = 0.940-0.993) with a cutoff value of 3.08. The cutoff value showed the greatest sensitivity (91.7%), specificity (68.4%), and AUC value (0.967) as a diagnostic tool for AOSD. The NLR and treatment appeared to be significant prognostic factors for relapse, but only age showed a significant relationship with death. Furthermore, the NLR was significantly higher in patients with macrophage activation syndrome than in hemophagocytic lymphohistiocytosis (HLH) patients (P = .007). In ROC analysis, the NLR with a cutoff value of 5.86 showed a sensitivity of 89.4%, specificity of 87.8%, and AUC of 0.794.The NLR can be used as a diagnostic tool and predictor of relapse in AOSD, and for differential diagnosis of HLH.

Objective.S100A12 and soluble receptor for advanced glycation endproducts (sRAGE) have been suggested as biomarkers of disease activity in patients with systemic juvenile idiopathic arthritis. We investigated the clinical significance of these markers in adult-onset Still’s disease (AOSD).Methods.Blood samples were collected from 37 patients with active AOSD and 38 healthy controls (HC). Of the patients with AOSD, followup samples were collected from 19 patients after resolution of disease activity.Results.Serum S100A12 (547.9 ± 148.4 ng/ml) in patients with AOSD was higher than those of HC (272.3 ± 133 ng/ml, p < 0.001). The sRAGE levels of AOSD (514.1 ± 273.6 pg/ml) were lower than those of HC (850.3 ± 405.8 pg/ml, p < 0.001). Serum S100A12 correlated with serum sRAGE (r = −0.228, p = 0.049). Serum S100A12 correlated with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin, and systemic score, whereas sRAGE did not correlate with any disease activity markers. In addition, the level of S100A12 was decreased after disease activity was resolved in followed-up patients with AOSD (505.7 ± 161.3 ng/ml vs 361.3 ± 162.5 ng/ml, p = 0.01). Further, the change of S100A12 was well correlated with that of ESR, CRP, and systemic score.Conclusion.S100A12 levels showed strong correlations with known disease activity markers such as ESR, CRP, ferritin, and systemic score. In the followup patients with AOSD, most patients showed decreased S100A12 levels after resolution of disease activity. These results suggest that serum S100A12 can be a reliable clinical marker for monitoring disease activity and treatment response.

Objective Anti-C-reactive protein (CRP) antibodies have been described in patients with systemic lupus erythematosus (SLE). We investigated the potential of the anti-CRP antibody as a marker for disease activity in SLE patients and as a predictor of progression to SLE in patients with incomplete lupus. Methods Immunoglobulin G anti-CRP antibody levels were measured using an enzyme-linked immunosorbent assay. Results Patients with incomplete lupus exhibited clinical and immunologic characteristics different from those in SLE patients: no serositis and alopecia, more common oral ulcers and arthritis, lower disease activity index, lower positivity for antinuclear and anti–double-strand DNA antibodies, and higher complement levels. Anti-CRP antibody levels were higher in SLE patients (35.6 [35.1] AU) than in patients with incomplete lupus (23.1 [25.8] AU, P = 0.016) and normal controls (21.0 [14.3] AU, P < 0.001). Anti-CRP antibody was significantly higher in SLE patients with arthritis and correlated with disease activity markers, including antichromatin antibody. However, no difference in anti-CRP antibody levels was observed between patients with incomplete lupus that progressed to SLE and those whose did not. Conclusion These data suggest that anti-CRP antibodies can neither be used as biomarkers in SLE nor predict SLE progression in patients with incomplete lupus.

The purposes of this study were to compare the perceived and actual 10-year risk for cardiovascular disease (CVD) and to evaluate the influence of cardiovascular risk factors on perceived CVD risk in patients with rheumatoid arthritis (RA) in Korea. Additionally, the attainment of CVD prevention guideline goals by 3 levels of CVD risk (low, moderate, and high) was presented. For this cross-sectional study, data were collected from 208 patients with RA. Actual CVD risk was estimated with the Systematic Coronary Risk Evaluation (SCORE), and goal attainment was assessed based on the European League Against Rheumatism guidelines. Actual CVD risk and perceived risk were compared with cross-tabulation. Chi-square tests were used to evaluate differences in cardiovascular risk factors by perceived risk. Levels of goal attainment were presented in percentages. Among patients with RA, 13.9% were identified as being at high risk for CVD, whereas 39.9% were at moderate risk, and 46.2% were at low risk. The majority of those at high risk (96.6%) underestimated their risk for CVD. The use of antihypertensive or lipid-lowering medications and having a parental history of CVD significantly increased the likelihood that subjects with RA would perceive themselves as being at high risk for CVD. Diabetes, smoking, physical inactivity, and obesity did not affect perceived risk. A substantial proportion of the subjects with RA did not meet the prevention guideline goals. Patients with RA who are at increased risk of developing CVD must be managed as soon as possible to attain the guideline goals and, accordingly, lower their risk of future CVD.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse manifestations, and its pathogenesis is unclear and complicated. Infection and SLE are similar in that they both cause inf lammatory reactions in the immune system; however, one functions to protect the body, whereas the other is activated to damage the body. Infection is known as one of the common trigger factors for SLE; there are a number of reports on infectious agents that provoke autoimmune response. Several viruses, bacteria, and protozoa were revealed to cause immune dysfunction by molecular mimicry, epitope spreading, and bystander activation. In contrast, certain pathogens were revealed to protect from immune dysregulation. Infection can be threatening to patients with SLE who have a compromised immune system, and it is regarded as one of the common causes of mortality in SLE. A clinical distinction between infection and lupus f lare up is required when patients with SLE present fevers. With a close-up assessment of symptoms and physical examination, C-reactive protein and disease activity markers play a major role in differentiating the different disease conditions. Vaccination is necessary because protection against infection is important in patients with SLE.

Backgrounds Patients who develop an active tuberculosis infection during tumor necrosis factor (TNF) inhibitor treatment typically discontinue TNF inhibitor and receive standard anti-tuberculosis treatment. However, there is currently insufficient information on patient outcomes following resumption of TNF inhibitor treatment during ongoing anti- tuberculosis treatment. Our study was designed to investigate the safety of resuming TNF inhibitors in ankylosing spondylitis (AS) patients who developed tuberculosis as a complication of the use of TNF inhibitors. Methods Through the nationwide registry of the Korean Society of Spondyloarthritis Research, 3929 AS patients who were prescribed TNF inhibitors were recruited between June 2003 and June 2014 at fourteen referral hospitals. Clinical information was analyzed about the patients who experienced tuberculosis after exposure to TNF inhibitors. The clinical features of resumers and non-resumers of TNF inhibitors were compared and the outcomes of tuberculosis were surveyed individually. Findings Fifty-six AS patients were treated for tuberculosis associated with TNF inhibitors. Among them, 23 patients resumed TNF inhibitors, and these patients were found to be exposed to TNF inhibitors for a longer period of time and experienced more frequent disease flare-up after discontinuation of TNF inhibitors compared with those who did not resume. Fifteen patients resumed TNF inhibitors during anti-tuberculosis treatment (early resumers) and 8 after completion of anti-tuberculosis treatment (late resumers). Median time to resuming TNF inhibitor from tuberculosis was 3.3 and 9.0 months in the early and late resumers, respectively. Tuberculosis was treated successfully in all resumers and did not relapse in any of them during follow-up (median 33.8 [IQR; 20.8-66.7] months). Conclusions Instances of tuberculosis were treated successfully in our AS patients, even when given concomitantly with TNF inhibitors. We suggest that early resumption of TNF inhibitors in AS patients could be safe under effective coverage of tuberculosis.

Psychological stress has been shown to trigger systemic lupus erythematosus (SLE). However, objective evidence of symptom aggravation due to mental stress is difficult to identify. We aimed to investigate the relationship between SLE disease activity and mental stress, and the usefulness of saliva as an assessment index for stress in patients with SLE. We prospectively assessed the salivary stress hormone and disease-related biomarkers, and questionnaire data regarding stress and depression in 100 patients with SLE and 49 sex- and age-matched normal controls (NCs). Patients with SLE had higher mean salivary α-amylase levels (5.7 ± 4.6 U/mL vs 2.7 ± 2.5 U/mL, P