Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study.

Objective: Genome-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.

Methods: We 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.

Optimum Urine Cotinine and NNAL Levels to Distinguish Smokers from Non-Smokers by the Changes in Tobacco Control Policy in Korea from 2008 to 2018.

Introduction: We examined the age- and sex-specific distributions of biomarkers of tobacco smoke exposure to determine the optimal cutoffs to distinguish smokers from non-smokers over the last 10 years in Korea, during which smoking prevalence and secondhand smoke (SHS) exposure declined due to changes in tobacco control policy.

Methods: We analyzed data from the Korea National Health and Nutrition Examination Survey on creatinine-adjusted urinary cotinine (2008-2018; 33 429 adults: 15 653 males and 17 776 females) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; 2016-2018; 6337 adults: 3091 males and 3246 females). We determined the optimal cutoffs and confidence intervals (CIs) to distinguish smokers from non-smokers using receiver operator characteristic curve analysis and bootstrapping (1000 resamples).

COX-2 Inhibitor Use as an Early Treatment Option for Knee Osteoarthritis Patients in Korea: A Population-Based Cross-Sectional Study.

Background: To investigate the use of cyclooxygenase-2 (COX-2) inhibitors as an initial drug treatment for knee osteoarthritis (OA) patients.

Methods: From 2013 to 2015, patients with knee OA were identified from the Korean nationwide claims database. Among them, we extracted incident cases of knee OA to identify the initial drug treatment.

Effect of resistance exercise on serum leptin levels in a prospective longitudinal study of women patients with rheumatoid arthritis.

Background: Exercise has an anti-inflammatory effect and reduces fat mass. Leptin has been known to be proinflammatory adipokines mainly produced by adipocytes. However, few studies have investigated the association between exercise and changes in serum leptin levels of patients with RA.

The effect of 24-week belimumab treatment withdrawal followed by treatment restart in patients with SLE: an open-label, non-randomised 52-week study.

Background: Treatment goals for patients with systemic lupus erythematosus (SLE) include minimising disease activity and reducing the risk of flares. Although belimumab is effective at reducing disease activity and risk of severe flares, it was previously unknown what the clinical effects were upon treatment discontinuation. The objective of this study was to assess the impact of temporary withdrawal of intravenous (IV) belimumab in patients with SLE.

Risk factors for herpes zoster in Korean patients with rheumatoid arthritis treated with JAK inhibitor: a nested case-control study.

Objective: To determine the risk of herpes zoster (HZ) in Korean patients with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKis).

Methods: We performed a nested case-control study with 1:10 matching for sex and age using single-centre prospective cohorts of patients with RA receiving targeted therapy in Korea. Then we performed conditional logistic regression analyses to determine the risk associated with JAKi use compared with biologic disease-modifying antirheumatic drug (bDMARD) use, with adjusting for various factors.

Evaluating the Construct of Damage in Systemic Lupus Erythematosus.

Objective: The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI.

WNT16 elevation induced cell senescence of osteoblasts in ankylosing spondylitis.

Background: WNT16 is critical for bone homeostasis, but the effect of WNT16 in ankylosing spondylitis (AS) is still unknown. Here, we investigated whether WNT16 influences bone formation and pathophysiological changes of AS in an in vitro model.

Methods: The bone tissue from the facet joints was obtained from seven disease control and seven AS patients.

SOX9 enthesis cells are associated with spinal ankylosis in ankylosing spondylitis.

Objective: Although cartilage degeneration and invasion of the subchondral bone plate in entheseal lesion has been considered to consequently lead bony ankylosis in ankylosing spondylitis (AS), no evident mechanisms are known.

Design: To identify histopathological and physiological changes in enthesitis-related ankylosis in AS, we performed molecular characterization of transcription factors and surface markers, and transcriptome analysis with human tissues. Entheseal tissue containing subchondral bone was obtained from the facet joints of 9 patients with AS and 10 disease controls, and assessed by using differential staining techniques.

Comparative Effectiveness of Azathioprine Versus Cyclosporine as an Initial Treatment for Idiopathic Inflammatory Myopathies: A Population-Based Observational Study.

Objective: To compare the effectiveness of azathioprine (AZA) and cyclosporine (CsA) as initial treatments for patients with idiopathic inflammatory myopathies (IIM).

Methods: A retrospective cohort study was conducted using information from the National Health Insurance Service database of Republic of Korea. Patients with IIM who had started AZA or CsA as initial treatment between January 2007 and December 2011 were selected for the study.

Recent advances in understanding the genetic basis of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a polygenic chronic autoimmune disease leading to multiple organ damage. A large heritability of up to 66% is estimated in SLE, with roughly 180 reported susceptibility loci that have been identified mostly by genome-wide association studies (GWASs) and account for approximately 30% of genetic heritability. A vast majority of risk variants reside in non-coding regions, which makes it quite challenging to interpret their functional implications in the SLE-affected immune system, suggesting the importance of understanding cell type-specific epigenetic regulation around SLE GWAS variants.

Fracture Risk and Its Prevention Patterns in Korean Patients with Polymyalgia Rheumatica: a Retrospective Cohort Study.

Background: To evaluate the incidence of fractures and fracture risk factors in Korean patients with polymyalgia rheumatica (PMR).

Methods: All PMR patients who visited a rheumatology clinic at a tertiary referral hospital between March 2005 and March 2018 were retrospectively assessed. We estimated bone mineral density (BMD) screening rate within 6 months of the first visit and classified the patients according to the performance and results of BMD screening.

Augmenting MNK1/2 activation by c-FMS proteolysis promotes osteoclastogenesis and arthritic bone erosion.

Osteoclasts are bone-resorbing cells that play an essential role in homeostatic bone remodeling and pathological bone erosion. Macrophage colony stimulating factor (M-CSF) is abundant in rheumatoid arthritis (RA). However, the role of M-CSF in arthritic bone erosion is not completely understood.

Impact of Infliximab Biosimilar CT-P13 Dose and Infusion Interval on Real-World Drug Survival and Effectiveness in Patients with Ankylosing Spondylitis.

CT-P13 is an infliximab biosimilar approved for indications including ankylosing spondylitis (AS); the approved maintenance regimen is 5 mg/kg infused every 6-8 weeks. In clinical practice, modifications to infliximab dose and/or infusion interval can be beneficial to the patient. For CT-P13, real-world data on dose and/or interval adjustment are lacking.

Urinary Concentrations of Bisphenol Mixtures during Pregnancy and Birth Outcomes: The MAKE Study.

Bisphenols are endocrine disruptors that may be associated with altered fetal growth in humans, and they have similar biological functions to mimic hormones. In addition, aggregated chemicals showed an adverse effect although individual concentration was at a low level. However, most studies between bisphenols and birth outcomes have focused on the effect of individual bisphenol.

Influence of serum ferritin combined with blood cadmium concentrations on blood pressure and hypertension: From the Korean National Health and Nutrition Examination Survey.

Background: Previous studies have suggested that cadmium (Cd) exposure and serum ferritin levels may influence the development of hypertension.

Objective: We evaluated whether the association between blood Cd levels and the development of hypertension could be modified by serum ferritin levels in a representative sample of the adult population of South Korea.

Methods: We used data from the Korean National Health and Nutrition Examination Survey (2008-2012), a nationally representative, cross-sectional, population-based study.

The TNF-NF-kB-DKK1 Axis Promoted Bone Formation in the Enthesis of Ankylosing Spondylitis.

Objective: This study aimed to determine the serum Dickkopf 1 (DKK1) levels in ankylosing spondylitis (AS) patients and decipher the mechanism of tumor necrosis factor (TNF)-mediated DKK1 regulation in human AS enthesis cells.

Methods: The sera were obtained from 103 patients with AS and 30 healthy controls (HCs) The enthesis of facet joints were obtained from 4 AS patients and 5 controls The serum levels of DKK1 were measured using ELISA and compared between AS and HCs The impact of TNF on DKK1 expression in human primary spinal enthesis cells was evaluated using various molecular biology techniques and bone formation indicators.

Results: AS patients showed higher serum DKK1 levels than HCs after adjusting for age (9174 [6153∼1,3100] pg/mL vs 8262 [6703∼9278] pg/mL, p=0043) TNF treatment promoted bone formation and DKK1 expression in both control enthesis cells and those of AS This enhanced bone formation by TNF was pronounced in AS-enthesis than those of controls Mechanically, TNF induced NF-B activation upregulates the DKK1 transcript level While, NF-B inhibitor led to downregulate DKK1 expression in the enthesis Besides, DKK1 overexpression promoted bone formation in enthesis.

Mortality in Korean Patients With Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which the abnormal immune system causes arthritis. We reviewed previous studies about the mortality and causes of death in Korean patients with RA. Also, we discussed the association between comorbidities and mortality in Korean patients with RA.

Clinical and Genetic Risk Factors Associated With the Presence of Lupus Nephritis.

Objective: To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN).

Methods: We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571) Baseline clinical features, serologic markers, and the wGRS were collected The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE Associations among clinical features, wGRS, and the presence of LN were identified.

Results: In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.

Blocking TNFα attenuates progressive cartilage matrix degradation in inflammatory arthritis.

Because damage to hyaline cartilage is irreversible, relieving progressive cartilage destruction is an important therapeutic approach for inflammatory arthritis. In the present study, human hyaline chondrocytes were isolated from total knee replacements of 15 patients with osteoarthritis (OA) and three with rheumatoid arthritis (RA). Synovial fluid of OA (n=25) and RA (n=34) were collected to measure tumor necrosis factor α (TNFα) using ELISA.

-Derived Protein Attenuates Inflammation and New Bone Formation in Ankylosing Spondylitis.

Helminth infections and their components have been shown to have the potential to modulate and attenuate immune responses. The objective of this study was to evaluate the potential protective effects of -derived protein (CSp) on ankylosing spondylitis (AS). Cytotoxicity of CSp at different doses was assessed by MTS and flow cytometry before performing experiments.