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Rheumatoid Arthritis: HELP
Articles by Ji-Hyeon Ju
Based on 56 articles published since 2010
(Why 56 articles?)
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Between 2010 and 2020, J. H. Ju wrote the following 56 articles about Arthritis, Rheumatoid.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial Can we calculate patients' compliance and forecast their adherence to medication: cultural adaptation of the Korean version of a compliance questionnaire for patients with rheumatoid arthritis. 2011

Ju, Ji Hyeon. · ·Korean J Intern Med · Pubmed #21437158.

ABSTRACT: -- No abstract --

2 Review Cytokine-mediated bone destruction in rheumatoid arthritis. 2014

Jung, Seung Min / Kim, Kyoung Woon / Yang, Chul-Woo / Park, Sung-Hwan / Ju, Ji Hyeon. ·Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-Gu, Seoul 137-701, Republic of Korea. · Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. · Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea ; Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-Gu, Seoul 137-701, Republic of Korea ; Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. ·J Immunol Res · Pubmed #25295284.

ABSTRACT: Bone homeostasis, which involves formation and resorption, is an important process for maintaining adequate bone mass in humans. Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation and bone loss, leading to joint destruction and deformity, and is a representative disease of disrupted bone homeostasis. The bone loss and joint destruction are mediated by immunological insults by proinflammatory cytokines and various immune cells. The connection between bone and immunity has been intensely studied and comprises the emerging field of osteoimmunology. Osteoimmunology is an interdisciplinary science investigating the interplay between the skeletal and the immune systems. The main contributors in osteoimmunology are the bone effector cells, such as osteoclasts or osteoblasts, and the immune cells, particularly lymphocytes and monocytes. Physiologically, osteoclasts originate from immune cells, and immune cells regulate osteoblasts and vice versa. Pathological conditions such as RA might affect these interactions, thereby altering bone homeostasis, resulting in the unfavorable outcome of bone destruction. In this review, we describe the osteoclastogenic roles of the proinflammatory cytokines and immune cells that are important in the pathophysiology of RA.

3 Review A case of leukoencephalopathy associated with adalimumab-treated rheumatoid arthritis and a review of literature. 2012

Ryu, Yang-Seon / Park, Sung-Hwan / Kim, Ji-Min / Kim, Eun-Ji / Lee, Jennifer / Kwok, Seung-Ki / Ju, Ji-Hyeon / Kim, Ho-Youn. ·Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. ·Rheumatol Int · Pubmed #22065075.

ABSTRACT: Tumor necrosis factor-alpha (TNF-alpha) inhibitor is recently being widely used to treat autoimmune diseases, but some noticeable adverse events were reported and neurological events have especially been described. It is mandatory to compare these cases for finding the risk factors, the duration of the neurological events, their processes and their outcomes. We present here the case of leukoencephalopathy secondary to adalimumab, which is a tumor necrosis factor α (TNF-α) inhibitor. We also reviewed the other 14 published leukoencephalopathy cases associated with the use of TNF inhibitors. Eleven patients had underlying rheumatoid arthritis, and the others had psoriatic arthritis, ankylosing spondylitis and Still's disease. The median duration of treatment with anti-TNF-α before the presentation of neurological symptoms was 9.2 months (range: 1.5-24). The duration of using anti-TNF-α was not related with the outcome. Although cases of neurological adverse events associated with anti-TNF-α treatment are rare, it is very important to monitor the neurological signs and symptoms suggestive of a demyelinating disorder in RA patients who are receiving anti-TNF-α treatment and especially those patients who are older and who have a history of MS or demyelination.

4 Article Metabolomic profiles of induced pluripotent stem cells derived from patients with rheumatoid arthritis and osteoarthritis. 2019

Kim, Juryun / Kang, Sunyoung Christina / Yoon, Na Eun / Kim, Yena / Choi, Jinhyeok / Park, Narae / Jung, Hyerin / Jung, Byung Hwa / Ju, Ji Hyeon. ·CiSTEM Laboratory, Catholic iPSC Research Center, College of Medicine, The Catholic University of Korea, Seoul, 137-701, South Korea. · Department of Life Sciences, McMaster University, 1280 Main St W, Hamilton, Canada. · Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea. · Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea. jbhluck@kist.re.kr. · Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, 02792, Republic of Korea. jbhluck@kist.re.kr. · CiSTEM Laboratory, Catholic iPSC Research Center, College of Medicine, The Catholic University of Korea, Seoul, 137-701, South Korea. juji@catholic.ac.kr. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Republic of Korea. juji@catholic.ac.kr. ·Stem Cell Res Ther · Pubmed #31730022.

ABSTRACT: BACKGROUND: Metabolomics is the systemic study of the unique fingerprints of metabolites involved in cellular processes and biochemical reactions. The metabolomic approach is useful in diagnosing and predicting the development of rheumatoid arthritis (RA) and osteoarthritis (OA) and is emerging as a useful tool for identifying disease biomarkers. The aim of this study was to compare the metabolic blueprint of fibroblast-like synoviocyte (FLS) cells and induced pluripotent stem cells (iPSCs) derived from RA and OA patients. METHODS: Somatic cells of RA patients (n = 3) and OA patients (n = 3) were isolated, transduced with a lentiviral plasmid, and reprogrammed into iPSCs displaying pluripotency. Metabolic profiling of RA and OA patient-derived FLS cells and iPSCs was performed using liquid chromatography/mass spectrometry and statistical analysis. After normalization by the sum of the peak intensities through LC/MS, 37 metabolites were detected across RA and OA patients. RESULTS: The metabolites of RA and OA were distinguishable according to the PLS-DA analysis. LysoPC (20:4), 4-methoxychalcone, phosphorylcholine, and nicotinamide (NAM) were significantly higher in RA iPSCs than in OA iPSCs (p < 0.05). The NMNAT-3 enzyme, which catalyzes an important step in the biosynthesis of NAD CONCLUSIONS: The metabolites of RA and OA FLS cells and RA and OA iPSCs were all clearly distinguishable from each other. NAM played a critical role in the proliferation of RA iPSCs but not in OA iPSCs. TA effectively inhibited the expression of NAM in RA iPSCs and is a possible effective treatment for RA patients.

5 Article Gut Microbial Composition and Function Are Altered in Patients with Early Rheumatoid Arthritis. 2019

Jeong, Yunju / Kim, Ji-Won / You, Hyun Ju / Park, Sang-Jun / Lee, Jennifer / Ju, Ji Hyeon / Park, Myeong Soo / Jin, Hui / Cho, Mi-La / Kwon, Bin / Park, Sung-Hwan / Ji, Geun Eog. ·Research Center, BIFIDO Co., Ltd., 23-16, Nonggongdanji-gil, Hongcheon 25117, Korea. tanklov0@snu.ac.kr. · Department of Food and Nutrition, Research Institute of Human Ecology, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Korea. tanklov0@snu.ac.kr. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul 137-701, Korea. shyqw@naver.com. · Department of Food and Nutrition, Research Institute of Human Ecology, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Korea. dhlover1@snu.ac.kr. · Institute of Health and Environment, Graduate School of Public Health, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Korea. dhlover1@snu.ac.kr. · Department of Food and Nutrition, Research Institute of Human Ecology, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Korea. sjpark-90@snu.ac.kr. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul 137-701, Korea. poohish@catholic.ac.kr. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul 137-701, Korea. juji@catholic.ac.kr. · Research Center, BIFIDO Co., Ltd., 23-16, Nonggongdanji-gil, Hongcheon 25117, Korea. bifidopark@bifido.com. · Department of Food and Nutrition, Research Institute of Human Ecology, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Korea. jh1030@snu.ac.kr. · Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul 137-040, Korea. iammila@catholic.ac.kr. · Research Center, BIFIDO Co., Ltd., 23-16, Nonggongdanji-gil, Hongcheon 25117, Korea. kb@bifido.com. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul 137-701, Korea. rapark@catholic.ac.kr. · Research Center, BIFIDO Co., Ltd., 23-16, Nonggongdanji-gil, Hongcheon 25117, Korea. geji@snu.ac.kr. · Department of Food and Nutrition, Research Institute of Human Ecology, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Korea. geji@snu.ac.kr. ·J Clin Med · Pubmed #31100891.

ABSTRACT: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation of the joints and extra-articular manifestations. Recent studies have shown that microorganisms affect RA pathogenesis. However, few studies have examined the microbial distribution of early RA patients, particularly female patients. In the present study, we investigated the gut microbiome profile and microbial functions in early RA female patients, including preclinical and clinically apparent RA cases. Changes in microbiological diversity, composition, and function in each group were analyzed using quantitative insights into microbial ecology (QIIME) and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). The results revealed the dysbiosis due to decreased diversity in the early RA patients compared with healthy subjects. There were significant differences in the microbial distribution of various taxa from phylum to genus levels between healthy subjects and early RA patients. Phylum Bacteroidetes was enriched in early RA patients, while Actinobacteria, including the genus

6 Article Sodium Chloride Aggravates Arthritis via Th17 Polarization. 2019

Jung, Seung Min / Kim, Youngkyun / Kim, Juryun / Jung, Hyerin / Yi, Hyoju / Rim, Yeri Alice / Park, Narae / Kwok, Seung Ki / Park, Sung Hwan / Ju, Ji Hyeon. ·Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. juji@catholic.ac.kr. ·Yonsei Med J · Pubmed #30554495.

ABSTRACT: PURPOSE: Sodium chloride (NaCl) has been proposed as a driving factor in autoimmune diseases through the induction of pathogenic CD4 MATERIALS AND METHODS: Collagen-induced arthritis (CIA) mice were fed a normal or high-salt diet RESULTS: NaCl increased murine and human Th17 cell differentiation in a dose-dependent manner. Clinical and histological arthritis was more severe in the high-salt-fed CIA mice, compared to control CIA mice. The proportion of Th17 cells among splenocytes was higher in CIA mice fed a high-salt diet. Expression of synovial and intestinal IL-17 was also higher in high-salt-fed CIA mice. Comparison of synovial fluid between RA patients and OA patients revealed that Na CONCLUSION: This study suggests that NaCl can aggravate arthritis by affecting Th17 differentiation. Accordingly, limiting salt intake may be helpful for treating inflammatory arthritis, such as RA.

7 Article Rheumatoid arthritis is associated with early tooth loss: results from Korea National Health and Nutrition Examination Survey V to VI. 2019

Kim, Ji-Won / Park, Jun-Beom / Yim, Hyeon Woo / Lee, Jennifer / Kwok, Seung-Ki / Ju, Ji Hyeon / Kim, Wan-Uk / Park, Sung-Hwan. ·Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. · Department of Periodontics, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. · Department of Preventive Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. ·Korean J Intern Med · Pubmed #30257550.

ABSTRACT: BACKGROUND/AIMS: To examine the association between rheumatoid arthritis (RA) and periodontitis or tooth loss. METHODS: The study used data from the fifth and sixth Korea National Health and Nutrition Examination Surveys conducted from 2010 to 2015. RA was defined as participant-reported physician-diagnosed RA that was being treated. Periodontitis and the number of natural teeth were determined by dental examination. Periodontitis was defined according to the community periodontal index (periodontal probing depth ≥ 4 mm). The association between RA and periodontitis or tooth loss was examined after controlling for confounding variables (e.g., age, smoking status, socioeconomic status, dental caries, frequency of toothbrushing, body mass index, alcohol consumption, and diabetes) in men and women. Subgroup analyses stratified by age were also performed. RESULTS: The study enrolled 20,297 participants aged ≥ 19 years (157 RA patients and 20,140 non-RA controls). There was no association between RA and periodontitis or tooth loss in men and women. Subgroup analyses in those aged < 60 years revealed a non-significant association between RA and periodontitis (adjusted odds ratio, 1.53; p = 0.162), but they revealed a significant association between RA and tooth loss (adjusted β, 0.20; p = 0.042). CONCLUSION: RA was not associated with periodontitis, but was associated with tooth loss in younger adults. Younger RA patients are more likely to suffer tooth loss than general younger population; thus dental management is required.

8 Article Risk of malignancy in patients with rheumatoid arthritis after anti-tumor necrosis factor therapy: results from Korean National Health Insurance claims data. 2019

Jung, Seung Min / Kwok, Seung-Ki / Ju, Ji Hyeon / Park, Yong-Beom / Park, Sung-Hwan. ·Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. · Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. ·Korean J Intern Med · Pubmed #29172405.

ABSTRACT: BACKGROUND/AIMS: Inhibition of tumor necrosis factor (TNF) is an effective treatment for rheumatoid arthritis (RA), but safety concerns about malignancy remain. The aim of this study was to evaluate cancer risk in RA patients treated with TNF inhibitors (TNFi), based on Korean Nationwide Health Insurance claims data. METHODS: Patients with seropositive RA were selected from the health insurance database containing all citizens' medical information, based on both RA diagnosis codes and medications. Between 2010 and 2014, RA patients treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and TNFi were enrolled and followed up. We compared the cancer incidence between patients treated with TNFi and csDMARDs using incidence rate ratios (IRRs) after adjustment for age, gender, and observational periods. RESULTS: Of 45,423 selected patients with seropositive RA, 2,337 were treated with TNFi and 43,086 were treated with csDMARDs. The TNFi group was younger and was followed-up for a longer duration. During the observational period, 1,732 and 49 cases of cancer were detected in patients treated with csDMARDs and TNFi, respectively. Old age and male sex were associated with cancer occurrence. Adjusted IRRs for all cancers and common cancers demonstrated that cancer incidence did not differ significantly between the TNFi group and csDMARDs group (IRR = 0.913 for all cancers, p = 0.546). CONCLUSION: This study revealed that cancer incidence was similar in RA patients treated with TNFi and csDMARDs. Anti-TNF therapy may be a safe therapeutic option for RA treatment, in terms of malignancy.

9 Article Recapitulation of methotrexate hepatotoxicity with induced pluripotent stem cell-derived hepatocytes from patients with rheumatoid arthritis. 2018

Kim, Juryun / Kim, Yena / Choi, Jinhyeok / Jung, Hyerin / Lee, Kijun / Kang, Jaewoo / Park, Narae / Rim, Yeri Alice / Nam, Yoojun / Ju, Ji Hyeon. ·CiSTEM laboratory, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Republic of Korea. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Institute of Medical Science, College of Medicine, The Catholic University of Korea, #505, Banpo-Dong, Seocho-Gu, Seoul, 137-701, Republic of Korea. · Department of Biomedicine & Health Sciences, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Republic of Korea. · CiSTEM laboratory, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Republic of Korea. juji@catholic.ac.kr. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Institute of Medical Science, College of Medicine, The Catholic University of Korea, #505, Banpo-Dong, Seocho-Gu, Seoul, 137-701, Republic of Korea. juji@catholic.ac.kr. ·Stem Cell Res Ther · Pubmed #30594247.

ABSTRACT: BACKGROUND: Methotrexate (MTX) is widely used for the treatment of rheumatoid arthritis (RA). The drug is cost-effective, but sometimes causes hepatotoxicity, requiring a physician's attention. In this study, we simulated hepatotoxicity by treating hepatocytes derived from RA patient-derived induced pluripotent stem cells (RA-iPSCs) with MTX. METHODS: RA-iPSCs and healthy control iPSCs (HC-iPSCs) were established successfully. RA-iPSCs were differentiated into hepatocytes in two-dimensional (2D) monolayers and three-dimensional (3D) hepatocyte spheroid cultures; this process required growth factors such as BMP4, bFGF, HGF, and OSM. Immunofluorescence staining and flow cytometry were performed to confirm that the mature hepatocytes expressed cytokeratin 18, anti-alpha-1 antitrypsin, and albumin. MTX toxicity was evaluated via monitoring of cell viability, alanine aminotransferase, and mitochondrial status after MTX treatment in 2D and 3D cultures. RESULTS: RA-iPSCs generated from three RA patients suffering from MTX-induced hepatotoxicity differentiated into the endoderm lineage, hepatoblasts, and hepatocytes. In 2D culture, RA-iPSC-derived hepatocytes were more sensitive to MTX than healthy controls. A 3D culture system using hepatocyte spheroids also successfully recapitulated MTX-induced hepatotoxicity. The 3D culture system had several advantages, including longer culture periods under more complex conditions. CONCLUSIONS: A patient-derived iPSC platform could recapitulate MTX toxicity. Simulation of drug toxicity in vitro may help clinicians choose safer drugs or less toxic doses.

10 Article Risk factors associated with inadequate control of disease activity in elderly patients with rheumatoid arthritis: Results from a nationwide KOrean College of Rheumatology BIOlogics (KOBIO) registry. 2018

Jung, Seung Min / Kwok, Seung-Ki / Ju, Ji Hyeon / Lee, Sang-Won / Song, Jason Jungsik / Yoon, Chong-Hyeon / Park, Yong-Beom / Park, Sung-Hwan. ·Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. · Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. ·PLoS One · Pubmed #30325962.

ABSTRACT: OBJECTIVE: The proportion of elderly patients with rheumatoid arthritis (RA) is continuously growing as a result of the increasing aging population. We compared disease activity between different age groups, and evaluated the clinical factors associated with high disease activity. METHODS: This cross-sectional study analyzed the data of RA patients enrolled in the Korean College of Rheumatology Biologics registry (KOBIO-RA) between 2012 and 2014. Disease activity between elderly (age ≥ 65 years) and non-elderly patients (age < 65 years) was compared, and the association of clinical factors with high disease activity was assessed using a multivariate logistic regression model. RESULTS: Of 1,227 patients in KOBIO-RA, 244 patients with RA were aged 65 years or over. In elderly patients, the proportion of men was higher (P = 0.012), and the duration of disease was longer (P < 0.001) compared with non-elderly patients. The elderly group showed a higher incidence of comorbidity (P < 0.001), and less use of methotrexate (P = 0.004). Assessment of disease activity using various composite measures showed a higher proportion of high disease activity in elderly patients than non-elderly patients. Longer disease duration, presence of comorbidity, and non-use of methotrexate were independently associated with high disease activity (P = 0.002, P < 0.001, and P = 0.029, respectively). CONCLUSIONS: At enrollment of KOBIO-RA, elderly patients showed higher disease activity compared with non-elderly patients. Disease duration, use of methotrexate, and comorbidity are associated with disease activity control in Korean patients with RA.

11 Article Performance of the 2016 ACR-EULAR classification criteria for primary Sjogren's syndrome in a Korean cohort. 2018

Lee, Jennifer / Koh, Jung Hee / Kim, Ji-Won / Sung, Yoon-Kyoung / Lee, Shin-Seok / Choe, Jung Yoon / Shim, Seung-Cheol / Kim, Hyun-Sook / Kim, Hae-Rim / Kim, Ji-Min / Kwon, Sung Ryul / Kim, Hyun-Ok / Shin, Kichul / Lee, Chang Hoon / Chung, So-Hyang / Kwok, Seung-Ki / Ju, Ji Hyeon / Park, Sung-Hwan. ·Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul, 137-701, Republic of Korea. · Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea. · Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea. · Division of Rheumatology, Daegu Catholic University Medical Center, Daegu, Republic of Korea. · Division of Rheumatology, Department of Internal Medicine, School of Medicine, Chungnam National University, Chungnam National University Hospital, Daejeon, Republic of Korea. · Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea. · Division of Rheumatology, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea. · Division of Rheumatology, Department of Internal Medicine, Keimyung University Dongsan Medical Centre, Daegu, Republic of Korea. · Division of Rheumatology, Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea. · Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea. · Division of Rheumatology, Department of Internal Medicine, SNU Boramae Medical Center, Seoul, Republic of Korea. · Department of Internal Medicine, Wonkwang University College of Medicine, Iksan, Republic of Korea. · Department of Ophthalmology and Visual Science, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul, 137-701, Republic of Korea. rapark@catholic.ac.kr. ·Rheumatol Int · Pubmed #30030624.

ABSTRACT: This study compared the performance of the newly proposed 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria to the 2002 American-European Consensus Group (AECG) and 2012 ACR classification criteria for primary Sjogren's syndrome (pSS) in well-characterized Korean patients. Patients with pSS from 12 university-affiliated hospitals in Korea were enrolled from October 2013 to January 2017. Clinical and laboratory data were reviewed. For the validation set, patients who underwent evaluation tests to rule out pSS at Seoul St. Mary's hospital from November 2016 to December 2017 were analyzed. Baseline registry data were available in 458 patients, and 328 patients had sufficient data to determine the fulfillment of each criteria set. All three sets of criteria were met by 307 patients (93.6%). The newly proposed 2016 ACR/EULAR criteria were met by 325 patients (99.1%). The 2002 AECG and 2012 ACR criteria were met by 325 (99.1%) and 310 patients (94.5%), respectively. In a validation cohort consisting of 161 patients with pSS-related symptoms/signs, the sensitivity and specificity of the 2016 ACR/EULAR criteria were 100% [95% confidence interval (CI), 96.11-100.00] and 81.8% [95% CI, 76.15-94.26], respectively. Agreement between the 2016 criteria and 2012 or 2002 criteria was high (Cohen's kappa 0.736 and 0.769, respectively). The newly proposed 2016 ACR/EULAR criteria were met by most patients diagnosed with pSS according to previous criteria and showed higher sensitivity and lower specificity compared with both previous criteria sets.

12 Article Kruppel-Like Factor 4 Positively Regulates Autoimmune Arthritis in Mouse Models and Rheumatoid Arthritis in Patients 2018

Choi, Seungjin / Lee, Kijun / Jung, Hyerin / Park, Narae / Kang, Jaewoo / Nam, Ki-Hoan / Kim, Eun-Kyeong / Ju, Ji Hyeon / Kang, Kwi Young. ·CiSTEM Laboratory, Catholic iPSC Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. · School of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, South Korea. · Department of Cancer Biomedical Science, Research Institute, National Cancer Center, Goyang, South Korea. · Laboratory Animal Resource Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Cheongju, South Korea. · Division of Rheumatology, Department of Internal Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, South Korea. ·Front Immunol · Pubmed #29997611.

ABSTRACT: Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes mild to severe joint inflammation. During RA pathogenesis, fibroblast-like synoviocytes (FLS) acquire a tumor-like phenotype and mediate cartilage destruction both directly and indirectly by producing proinflammatory cytokines and matrix metalloproteinases (MMPs). Kruppel-like factor (KLF) 4, a member of the KLF family, plays significant roles in cell survival, proliferation, and differentiation. A recent study reported increased expression of KLF4 in synovial tissue from RA patients. However, its precise role in RA in different models, including mouse autoimmune disease models, remains unclear. In this study, we examined the role of KLF4 during development of autoimmune arthritis in mouse models. To do this, we used KLF4 knockout mice rendered by ribonucleic acid (RNA)-guided endonuclease (RGEN) and performed collagen antibody-induced arthritis (CAIA). We found that deletion of KLF4 reduces inflammation induced by CAIA. In addition, we assessed collagen-induced arthritis (CIA) in control mice and KLF4-overexpressing mice generated by a minicircle vector treatment. Severity of CIA in mice overexpressing KLF4 was greater than that in mice injected with control vector. Finally, we verified the inflammatory roles of KLF4 in CIA by treating Kenpaullone which is used as KLF4 inhibitor. Next, we focused on human/mouse FLS to discover the cellular process involved in RA pathogenesis including proliferation, apoptosis, and inflammation including MMPs. In FLS, KLF4 upregulated expression of mRNA encoding proinflammatory cytokines interleukin (IL)-1β and IL-6. KLF4 also regulated expression of matrix metallopeptidase 13 in the synovium. We found that blockade of KLF4 in FLS increased apoptosis and suppressed proliferation followed by downregulation of antiapoptotic factor BCL2. Our results indicate that KLF4 plays a crucial role in pathogenesis of inflammatory arthritis

13 Article Interrupting oral infection of Porphyromonas gingivalis with anti-FimA antibody attenuates bacterial dissemination to the arthritic joint and improves experimental arthritis. 2018

Jeong, Sang Hoon / Nam, Yoojun / Jung, Hyerin / Kim, Juryun / Rim, Yeri Alice / Park, Narae / Lee, Kijun / Choi, Seungjin / Jang, Yeonsue / Kim, Yena / Moon, Ji-Hoi / Jung, Seung Min / Park, Sung-Hwan / Ju, Ji Hyeon. ·Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. · Department of Maxillofacial Biomedical Engineering, School of Dentistry, and Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, South Korea. ·Exp Mol Med · Pubmed #29568073.

ABSTRACT: Rheumatoid arthritis (RA) is a chronic autoimmune disease that typically results in strong inflammation and bone destruction in the joints. It is generally known that the pathogenesis of RA is linked to cardiovascular and periodontal diseases. Though rheumatoid arthritis and periodontitis share many pathologic features such as a perpetual inflammation and bone destruction, the precise mechanism underlying a link between these two diseases has not been fully elucidated. Collagen-induced arthritis (CIA) mice were orally infected with Porphyromonas gingivalis (Pg) or Pg preincubated with an anti-FimA antibody (FimA Ab) specific for fimbriae that are flexible appendages on the cell surface. Pg-infected CIA mice showed oral microbiota disruption and increased alveolar bone loss and had synovitis and joint bone destruction. However, preincubation with FimA Ab led to a significant reduction in the severity of both oral disease and arthritis. Moreover, FimA Ab attenuated bacterial attachment and aggregation on human gingival and rheumatoid arthritis synovial fibroblasts. In addition, we discovered bacteria may utilize dendritic cells, macrophages and neutrophils to migrate into the joints of CIA mice. These results suggest that disrupting Pg fimbriae function by FimA Ab ameliorates RA.

14 Article Safety, and Humoral and Cell-mediated Immune Responses to Herpes Zoster Vaccine in Patients with Rheumatoid Arthritis. 2018

Koh, Jung Hee / Lee, Jaeseon / Kim, Seo Hwa / Kwok, Seung-Ki / Ju, Ji Hyeon / Park, Sung-Hwan. ·From the Division of Rheumatology, Department of Internal Medicine, St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. · J.H. Koh, MD, Division of Rheumatology, Department of Internal Medicine, St. Mary's Hospital, College of Medicine, The Catholic University of Korea; S.H. Kim, MD, Division of Rheumatology, Department of Internal Medicine, St. Mary's Hospital, College of Medicine, The Catholic University of Korea; S.K. Kwok, MD, PhD; Division of Rheumatology, Department of Internal Medicine, St. Mary's Hospital, and Rheumatism Research Center, College of Medicine, The Catholic University of Korea; J.H. Ju, MD, PhD, Division of Rheumatology, Department of Internal Medicine, St. Mary's Hospital, College of Medicine, The Catholic University of Korea; S.H. Park, MD, PhD, Division of Rheumatology, Department of Internal Medicine, St. Mary's Hospital, and Rheumatism Research Center, College of Medicine, The Catholic University of Korea; J. Lee, MS, Rheumatism Research Center, College of Medicine, The Catholic University of Korea. · From the Division of Rheumatology, Department of Internal Medicine, St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. rapark@catholic.ac.kr. · J.H. Koh, MD, Division of Rheumatology, Department of Internal Medicine, St. Mary's Hospital, College of Medicine, The Catholic University of Korea; S.H. Kim, MD, Division of Rheumatology, Department of Internal Medicine, St. Mary's Hospital, College of Medicine, The Catholic University of Korea; S.K. Kwok, MD, PhD; Division of Rheumatology, Department of Internal Medicine, St. Mary's Hospital, and Rheumatism Research Center, College of Medicine, The Catholic University of Korea; J.H. Ju, MD, PhD, Division of Rheumatology, Department of Internal Medicine, St. Mary's Hospital, College of Medicine, The Catholic University of Korea; S.H. Park, MD, PhD, Division of Rheumatology, Department of Internal Medicine, St. Mary's Hospital, and Rheumatism Research Center, College of Medicine, The Catholic University of Korea; J. Lee, MS, Rheumatism Research Center, College of Medicine, The Catholic University of Korea. rapark@catholic.ac.kr. ·J Rheumatol · Pubmed #29419465.

ABSTRACT: OBJECTIVE: To examine humoral and cellular immune responses induced by a live attenuated herpes zoster (HZ) vaccine in patients with rheumatoid arthritis (RA) compared with osteoarthritis (OA) patients. METHODS: This was an observational study of a live attenuated HZ vaccine in 41 patients with RA receiving conventional disease-modifying antirheumatic drugs (cDMARD) and/or low-dose glucocorticoids (GC) and in 28 patients with OA. Blood samples were obtained before and at 12 weeks after HZ vaccination. Immunogenicity was assessed using varicella zoster virus (VZV)-specific interferon gamma ELISA and an in-house ELISA. Clinical outcomes, including adverse events, HZ occurrence, and RA flares, were analyzed. RESULTS: No patients developed vaccination-induced HZ during the followup period (median = 1.6 yrs). The HZ vaccine induced a significant increase in the VZV-specific enzyme-linked immunospot spot-forming units and anti-VZV immunoglobulin G antibodies in patients with RA and OA. The number of spot-forming units was lower in patients with RA than in patients with OA both at baseline and at 12 weeks after vaccination. The disease activity index for patients with RA was similar at baseline and at 12 weeks after vaccination. However, 6 patients with RA (14.6%) experienced a flare during the 12 weeks. Overall, 17 (24.6%) participants reported a mild adverse event such as an injection site reaction (11.6%). CONCLUSION: The HZ vaccine induced VZV-specific cellular and humoral responses in patients with RA. Although patients with RA showed a weaker vaccine-induced VZV-specific cellular immune response than patients with OA, the vaccine may be considered in patients with RA receiving cDMARD and/or low dose GC.

15 Article Predisposing factors associated with atypical femur fracture among postmenopausal Korean women receiving bisphosphonate therapy: 8 years' experience in a single center. 2017

Koh, J H / Myong, J P / Yoo, J / Lim, Y-W / Lee, J / Kwok, S-K / Park, S-H / Ju, J H. ·Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-040, South Korea. · Department of Occupational & Environmental Medicine, Center for Occupational & Environmental Medicine (WHO Collaboratory Center), Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. · Department of Orthopedic Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-040, South Korea. juji@catholic.ac.kr. ·Osteoporos Int · Pubmed #28748389.

ABSTRACT: The risk factors for atypical femur fracture in patients exposed to bisphosphonates for at least 1 year were examined. Prolonged and continuous use of bisphosphonates, long-term use of glucocorticoids, and a higher body mass index were associated with increased risk of atypical femur fracture. INTRODUCTION: The purpose of the present study is to determine whether rheumatoid arthritis (RA) and other clinical factors are associated with an increased risk of bisphosphonate (BP)-related atypical femur fracture (AFF). METHODS: A retrospective nested case-control study of patients who had taken BPs for at least 1 year was conducted. Patients with AFF were identified by reviewing surgical and radiographic records. Three controls with no history of AFFs were randomly selected and age- and sex-matched to each patient with AFFs. Cox proportional hazard models were used to analyze the independent contribution of risk factors to BP-related AFF. RESULTS: Among the 35,104 patients prescribed BPs for at least 1 year, 43 females (mean age, 68 years) suffered AFFs (0.12%). Patients with AFFs were exposed to BPs for a mean of 7.3 years. Patients with AFFs were exposed to BPs for longer than those without AFFs and continued treatment without a drug holiday. More patients with AFF than controls had taken glucocorticoids and disease-modifying anti-rheumatic drugs. Multivariate Cox regression analyses estimated that long-term use of glucocorticoids, prolonged exposure to BP without cessation, and every 1 kg/m CONCLUSIONS: Prolonged and continuous use of BPs, long-term use of glucocorticoids, and a higher BMI increase the risk of AFFs. Switching long-term BP and glucocorticoid users to other bone-protective agents should be considered.

16 Article Generation of Induced-pluripotent Stem Cells Using Fibroblast-like Synoviocytes Isolated from Joints of Rheumatoid Arthritis Patients. 2016

Rim, Yeri Alice / Park, Narae / Nam, Yoojun / Ju, Ji Hyeon. ·CiSTEM Laboratory, Convergent Research Consortium for Immunologic Disease, Division of Rheumatology, Seoul St. Mary's Hospital, Republic of Korea; College of Medicine, The Catholic University of Korea, Republic of Korea. · CiSTEM Laboratory, Convergent Research Consortium for Immunologic Disease, Division of Rheumatology, Seoul St. Mary's Hospital, Republic of Korea. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Institute of Medical Science, Republic of Korea; College of Medicine, The Catholic University of Korea, Republic of Korea; juji@catholic.ac.kr. ·J Vis Exp · Pubmed #27805584.

ABSTRACT: Mature somatic cells can be reversed into a pluripotent stem cell-like state using a defined set of reprogramming factors. Numerous studies have generated induced-Pluripotent Stem Cells (iPSCs) from various somatic cell types by transducing four Yamanaka transcription factors: Oct4, Sox2, Klf4 and c-Myc. The study of iPSCs remains at the cutting edge of biological and clinical research. In particular, patient-specific iPSCs can be used as a pioneering tool for the study of disease pathobiology, since iPSCs can be induced from the tissue of any individual. Rheumatoid arthritis (RA) is a chronic inflammatory disease, classified by the destruction of cartilage and bone structure in the joint. Synovial hyperplasia is one of the major reasons or symptoms that lead to these results in RA. Fibroblast-like Synoviocytes (FLSs) are the main component cells in the hyperplastic synovium. FLSs in the joint limitlessly proliferate, eventually invading the adjacent cartilage and bone. Currently, the hyperplastic synovium can be removed only by a surgical procedure. The removed synovium is used for RA research as a material that reflects the inflammatory condition of the joint. As a major player in the pathogenesis of RA, FLSs can be used as a material to generate and investigate the iPSCs of RA patients. In this study, we used the FLSs of a RA patient to generate iPSCs. Using a lentiviral system, we discovered that FLSs can generate RA patient-specific iPSC. The iPSCs generated from FLSs can be further used as a tool to study the pathophysiology of RA in the future.

17 Article Generation of Functional Cardiomyocytes from the Synoviocytes of Patients with Rheumatoid Arthritis via Induced Pluripotent Stem Cells. 2016

Lee, Jaecheol / Jung, Seung Min / Ebert, Antje D / Wu, Haodi / Diecke, Sebastian / Kim, Youngkyun / Yi, Hyoju / Park, Sung-Hwan / Ju, Ji Hyeon. ·Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. · Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA. · Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA. · Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. · Department of Cardiology and Pneumonology, Göttingen University Medical Center, Göttingen, Germany. · DZHK (German Center for Cardiovascular Research), partner site Göttingen, Germany. · Max Delbrück Center, Berlin, Germany Berlin Institute of Health, Berlin, Germany. · Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. ·Sci Rep · Pubmed #27609119.

ABSTRACT: Cardiovascular disease is a leading cause of morbidity in rheumatoid arthritis (RA) patients. This study aimed to generate and characterise cardiomyocytes from induced pluripotent stem cells (iPSCs) of RA patients. Fibroblast-like synoviocytes (FLSs) from patients with RA and osteoarthritis (OA) were successfully reprogrammed into RA-iPSCs and OA-iPSCs, respectively. The pluripotency of iPSCs was confirmed by quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining. Established iPSCs were differentiated into cardiomyocytes using a small molecule-based monolayer differentiation protocol. Within 12 days of cardiac differentiation from patient-specific and control-iPSCs, spontaneously beating cardiomyocytes (iPSC-CMs) were observed. All iPSC-CMs exhibited a reliable sarcomeric structure stained with antibodies against cardiac markers and similar expression profiles of cardiac-specific genes. Intracellular calcium signalling was recorded to compare calcium-handling properties among cardiomyocytes differentiated from the three groups of iPSCs. RA-iPSC-CMs had a lower amplitude and a shorter duration of calcium transients than the control groups. Peak tangential stress and the maximum contractile rate were also decreased in RA-iPSC-CMs, suggesting that contractility was reduced. This study demonstrates the successful generation of functional cardiomyocytes from pathogenic synovial cells in RA patients through iPSC reprogramming. Research using RA-iPSC-CMs might provide an opportunity to investigate the pathophysiology of cardiac involvement in RA.

18 Article IL-1 receptor antagonist (IL-1Ra)-Fc ameliorate autoimmune arthritis by regulation of the Th17 cells/Treg balance and arthrogenic cytokine activation. 2016

Lee, Seon-Yeong / Min, Hong Ki / Lee, Seung Hoon / Shin, Hye Jeong / Lee, Woon Young / Cho, Young-Gyu / Kwok, Seung-Ki / Ju, Ji Hyeon / Cho, Mi-La / Park, Sung-Hwan. ·Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, South Korea. Electronic address: seonyeong@catholic.ac.kr. · Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, South Korea; Division of Rheumatology, Department of internal Medicine, School of Medicine, The Catholic University of Korea, Seoul 137-070, South Korea. Electronic address: alsghdrl1921@naver.com. · Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, South Korea. Electronic address: redcap817@catholic.ac.kr. · HANDOK Inc. 132, Theheran street, Gangnam-gu, Seoul 135-755, South Korea. Electronic address: hyejeong.shin@handok.com. · HANDOK Inc. 132, Theheran street, Gangnam-gu, Seoul 135-755, South Korea. Electronic address: woonyoung.lee@handok.com. · HANDOK Inc. 132, Theheran street, Gangnam-gu, Seoul 135-755, South Korea. Electronic address: younggyu.cho@handok.com. · Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, South Korea; Division of Rheumatology, Department of internal Medicine, School of Medicine, The Catholic University of Korea, Seoul 137-070, South Korea. Electronic address: seungki73@catholic.ac.kr. · Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, South Korea; Division of Rheumatology, Department of internal Medicine, School of Medicine, The Catholic University of Korea, Seoul 137-070, South Korea. Electronic address: juji@catholic.ac.kr. · Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, South Korea. Electronic address: iammila@catholic.ac.kr. · Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, South Korea; Division of Rheumatology, Department of internal Medicine, School of Medicine, The Catholic University of Korea, Seoul 137-070, South Korea. Electronic address: rapark@catholic.ac.kr. ·Immunol Lett · Pubmed #26903194.

ABSTRACT: INTRODUCTION: IL-1β signalling has a critical role in the pathogenesis of various types of inflammatory arthritis including rheumatoid arthritis (RA). We aimed to investigate the therapeutic effects of human IL-1 receptor antagonist with Fc fragment (hIL-1Ra-Fc) on autoimmune arthritis and to identify the possible mechanisms by which hIL-1RA-Fc exerts anti-arthritic effects in a murine model of RA and patients with rheumatoid arthritis. METHODS: Collagen-induced arthritis (CIA) murine model was established in DBA/1J mice. The levels of various cytokines were determined by using enzyme-linked immunosorbent assay. The mouse joints were assessed for clinical arthritis score and histologic features. Th17 cells and Treg cells were stained by using antibodies specific for CD4, IL-17, CD25, and FoxP3. Osteoclastogenesis was determined by TRAP staining and real-time PCR. RESULTS: hIL-1RA-Fc reduced the arthritis incidence, histological inflammation and cartilage score in the CIA model. The expression of proinflammatory cytokines, VEGF and RANK, was reduced in the affected joint of hIL-1Ra-Fc-treated mice. hIL-1Ra-Fc-treated mice showed decreased number of Th17 cells with increased number of Treg cells in spleens. hIL-1Ra-Fc reduced Th17 cell differentiation by inactivation of STAT3 signalling, and reciprocally induced Treg cell differentiation through STAT5 signalling. In addition, the expression of IL-17, TNF-α, RANKL, and VEGF was decreased, while Foxp3 gene expression was increased in PBMCs of RA patients after administration of hIL-1Ra-Fc. CONCLUSION: The anti-arthritis effects of hIL-1RA-Fc are associated with regulation of balance between Th17 cells and Treg cells and suppression of osteoclastogenesis and angiogenesis in the affected joints.

19 Article A Dual Target-directed Agent against Interleukin-6 Receptor and Tumor Necrosis Factor α ameliorates experimental arthritis. 2016

Kim, Youngkyun / Yi, Hyoju / Jung, Hyerin / Rim, Yeri Alice / Park, Narae / Kim, Juryun / Jung, Seung Min / Park, Sung-Hwan / Park, Young Woo / Ju, Ji Hyeon. ·CiSTEM laboratory, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 137-701, South Korea. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 137-701, South Korea. · Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, South Korea. ·Sci Rep · Pubmed #26841833.

ABSTRACT: A considerable proportion of patients with rheumatoid arthritis (RA) do not respond to monospecific agents. The purpose of our study was to generate a hybrid form of biologics, targeting tumor-necrosis factor alpha (TNFα) and interleukin-6 receptor (IL-6R), and determine its anti-arthritic properties in vitro and in vivo. A novel dual target-directed agent (DTA(A7/sTNFR2)) was generated by conjugating soluble TNF receptor 2 (sTNFR2) to the Fc region of A7, a new anti-IL-6R antibody obtained by screening the phage display human antibody library. DTA(A7/sTNFR2) inhibited the proliferation and migration of fibroblast-like synoviocytes from patients with RA (RA-FLS) more efficiently than single target-directed agents. DTA(A7/sTNFR2) also blocked osteoclastogenesis from bone marrow cells. The arthritis severity scores of the experimental arthritis mice with DTA(A7/sTNFR2) tended to be lower than those of mice with IgG, A7, or sTNFR2. Histological data suggested that DTA(A7/sTNFR2) is more efficient than single-target drugs in preventing joint destruction and bone loss. These results were confirmed in vivo using the minicircle system. Taken together, the results show that DTA(A7/sTNFR2) may be a promising therapeutic agent for the treatment of RA.

20 Article Atypical Femoral Fracture in Rheumatoid Arthritis Patients Treated With Bisphosphonates: A Nested Case-Control Study. 2016

Koh, Jung Hee / Myong, Jun Pyo / Jung, Seung Min / Lee, Jennifer / Kwok, Seung-Ki / Park, Sung-Hwan / Ju, Ji Hyeon. ·Seoul St. Mary's Hospital and Catholic University of Korea, Seoul, Republic of Korea. ·Arthritis Rheumatol · Pubmed #26360133.

ABSTRACT: OBJECTIVE: To examine the clinical characteristics of atypical femoral fracture (AFF) and to determine the risk factors for and clinical outcomes of AFFs in rheumatoid arthritis (RA) patients treated with bisphosphonates (BPs). METHODS: A nested case-control study was conducted using data derived from the medical records of all RA patients treated with BPs at Seoul St. Mary's Hospital, a tertiary rheumatology center, from January 1, 2008 to December 31, 2014. All of the patients with RA and had been treated with BPs for at least 1 year. Ten RA patients with AFF were identified, and each of these patients (cases) was age- and sex-matched with 4 RA patients without AFF (controls). RESULTS: Five hundred fifty-two RA patients had BP exposure. Of the 10 with AFF, all were female (mean ± SD age 66.3 ± 8.7 years), and 90% of cases involved fracture of the proximal femur. The mean ± SD length of BP exposure in patients with AFF was 7.4 ± 3.2 years. Compared with controls, patients with AFF had a longer exposure to BPs and more often had a femorotibial angle of <175 degrees (both P < 0.001). There were no differences in RA duration, medications taken during the previous 6 months, and bone mineral density in the femur and lumbar spine between patients with and those without AFF. Multivariate logistic analyses identified longer BP exposure (odds ratio 2.386 [95% confidence interval 1.066-5.343]) as being associated with an increased risk of AFF. CONCLUSION: RA patients who have a valgus deformity and are receiving long-term BP treatment are at higher risk of AFF compared with matched control patients with RA. These patients should be carefully followed up with hip radiography or dual x-ray absorptiometry.

21 Article Downregulation of Tryptophan-related Metabolomic Profile in Rheumatoid Arthritis Synovial Fluid. 2015

Kang, Kwi Young / Lee, Soo Hyun / Jung, Seung Min / Park, Sung-Hwan / Jung, Byung-Hwa / Ju, Ji Hyeon. ·From the Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul; Division of Rheumatology, Department of Internal Medicine, College of Medicine, Incheon Saint Mary's Hospital, The Catholic University of Korea, Incheon; Department of Medical Records and Health Information Management, College of Nursing and Health, Kongju National University, Chungnam; Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul; Division of Biological Chemistry, University of Science and Technology, Daejeon, South Korea.K.Y. Kang, PhD, Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Division of Rheumatology, Department of Internal Medicine, College of Medicine, Incheon Saint Mary's Hospital, The Catholic University of Korea; S.H. Lee, PhD, Department of Medical Records and Health Information Management, College of Nursing and Health, Kongju National University; S.M. Jung, MD; S.H. Park, PhD, Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea; B.H. Jung, PhD, Molecular Recognition Research Center, Korea Institute of Science and Technology, Division of Biological Chemistry, University of Science and Technology; J.H. Ju, PhD, Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea. ·J Rheumatol · Pubmed #26329338.

ABSTRACT: OBJECTIVE: Synovial fluid (SF) is one of the most important materials that reflect the pathophysiological process of arthritis. A metabolomic and lipidomic study of SF was performed with the aim of identifying tentative diagnostic markers or therapeutic candidates for rheumatoid arthritis (RA). METHODS: SF was aspirated from 10 patients with RA and 10 patients with osteoarthritis (OA). RA SF and OA SF were collected and analyzed by ultraperformance liquid chromatography quadruple time-of-flight mass spectrometry. Associations among clinical variables, laboratory results, and metabolic profiles were investigated. RESULTS: The metabolic pathways for carnitine, tryptophan, phenylalanine, arachidonic acid, and glycophospholipid were significantly upregulated in OA SF. The metabolic pathways for taurine, cholesterol ester, and the β-oxidation of pristine acid, linolenic acid, and sphingolipid were activated more in RA SF than in OA SF. In particular, the tryptophan pathway, which comprises kynurenine, indoleacetic acid, indole acetaldehyde, and N'-formylkynurenine, was downregulated. Interestingly, the levels of tryptophan metabolites kynurenine and N'-formylkynurenine, which are involved in immune tolerance, were significantly lower in RA SF compared with OA SF (p < 0.05), but the opposite pattern was observed for erythrocyte sedimentation rate (p < 0.01) and the levels of C-reactive protein (CRP; p < 0.01), rheumatoid factor (p < 0.01), and anticyclic citrullinated peptide antibody (p < 0.05). Kynurenine concentration correlated inversely with CRP concentration in RA SF but not in OA SF (r -0.65, p < 0.05). CONCLUSION: Advances in metabolomic techniques enabled us to delineate distinctive metabolic and lipidomic profiles in RA SF and OA SF. RA SF and OA SF showed distinct metabolic profiles.

22 Article Radiographic Structural Damage Is Worse in the Dominant than the Non-Dominant Hand in Individuals with Early Rheumatoid Arthritis. 2015

Koh, Jung Hee / Jung, Seung Min / Lee, Jennifer Jooha / Kang, Kwi Young / Kwok, Seung-Ki / Park, Sung-Hwan / Ju, Ji Hyeon. ·Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea. ·PLoS One · Pubmed #26247204.

ABSTRACT: OBJECTIVE: The relationship between mechanical stress and radiographic progression in rheumatoid arthritis (RA) is unclear. The assumption is that mechanical stress is greater in the dominant hand. Therefore, the aim of the present study was to compare the presence and progression of erosions and joint space narrowing (JSN) in the dominant and non-dominant hand. METHODS: Data from 194 patients recently diagnosed with seropositive RA, and with hand radiographs taken at the time of diagnosis and at 2-year follow-up, were analyzed retrospectively. Radiographs were scored using the van der Heijde-modified Sharp Score (HSS) method. Each joint group within each hand was rated separately by two independent examiners in a double-blinded manner. RESULTS: One hundred and ninety-four patients were enrolled (80% female, 88% positive rheumatoid factor, 92% positive anti-citrullinated protein antibody, and 95.4% right-handed). The baseline, follow-up erosion and JSN HSS were significantly higher in the dominant hand than in the non-dominant hand. The annual rate of radiographic progression was also higher in the dominant hand. The erosive progression in the wrist joints varied significantly according to handedness, but the erosion in the proximal interphalangeal joints and metacarpophalangeal joints was similar in both hands. The radiographic progression was associated with the dominant hand, an abnormal baseline C-reactive protein level, and joint damage at baseline. There was no significant difference in bone mineral density between the right and left hands. CONCLUSION: Radiological damage was worse and progressed faster in the dominant hand, suggesting that mechanical stress is associated with radiographic joint damage in early and active RA.

23 Article Eupatilin ameliorates collagen induced arthritis. 2015

Kim, Juryun / Kim, Youngkyun / Yi, Hyoju / Jung, Hyerin / Rim, Yeri Alice / Park, Narae / Jung, Seung Min / Park, Sung-Hwan / Ju, Ji Hyeon. ·Clinical Immunology and STEM (CiSTEM) Cell Laboratory, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. · Clinical Immunology and STEM (CiSTEM) Cell Laboratory, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. ; Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. · Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. ·J Korean Med Sci · Pubmed #25729243.

ABSTRACT: Eupatilin is the main active component of DA-9601, an extract from Artemisia. Recently, eupatilin was reported to have anti-inflammatory properties. We investigated the anti-arthritic effect of eupatilin in a murine arthritis model and human rheumatoid synoviocytes. DA-9601 was injected into collagen-induced arthritis (CIA) mice. Arthritis score was regularly evaluated. Mouse monocytes were differentiated into osteoclasts when eupatilin was added simultaneously. Osteoclasts were stained with tartrate-resistant acid phosphatase and then manually counted. Rheumatoid synoviocytes were stimulated with TNF-α and then treated with eupatilin, and the levels of IL-6 and IL-1β mRNA expression in synoviocytes were measured by RT-PCR. Intraperitoneal injection of DA-9601 reduced arthritis scores in CIA mice. TNF-α treatment of synoviocytes increased the expression of IL-6 and IL-1β mRNAs, which was inhibited by eupatilin. Eupatilin decreased the number of osteoclasts in a concentration dependent manner. These findings, showing that eupatilin and DA-9601 inhibited the expression of inflammatory cytokines and the differentiation of osteoclasts, suggest that eupatilin and DA-9601 is a candidate anti-inflammatory agent.

24 Article A pathogenetic role for IL-21 in primary Sjögren syndrome. 2015

Kwok, Seung-Ki / Lee, Jennifer / Yu, Di / Kang, Kwi Young / Cho, Mi-La / Kim, Hae-Rim / Ju, Ji Hyeon / Lee, Sang-Heon / Park, Sung-Hwan / Kim, Ho-Youn. ·Division of Rheumatology, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul 137-701, Republic of Korea. · Laboratory for Molecular Immunomodulation, School of Biomedical Sciences, Monash University, Clayton, VIC 3800, Australia. · The Rheumatism Research Centre, Catholic Research Institute of Medical Science, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul 137-701, Republic of Korea. · Division of Rheumatology, Department of Internal Medicine, Konkuk University School of Medicine, 120-1 Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul 143-729, South Korea. · Konkuk University Medical Centre, 120-1 Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul 143-729, South Korea. ·Nat Rev Rheumatol · Pubmed #25584898.

ABSTRACT: Advances in our understanding of the pathogenesis of primary Sjögren syndrome (pSS) characterize it as a highly complex process encompassing both the initiation of innate immunity and subsequent adaptive immune responses. IL-21 is receiving attention as a potential key player in the pathogenesis of pSS owing to its pleiotropic effects on the type I interferon signalling pathway, and newly identified roles in generation of follicular and IL-17-producing subtypes of helper T cells, as well as plasma-cell differentiation and B-cell activation. Taking into consideration the diverse biological functions of IL-21 and its clinical relevance to pSS, we propose that this cytokine has a central role in orchestrating the complex immune response in pSS. This hypothesis might provide new insight into the pathogenesis of pSS and facilitate the development of effective therapeutic strategies.

25 Article Risk of tuberculosis in patients treated with anti-tumor necrosis factor therapy: a nationwide study in South Korea, a country with an intermediate tuberculosis burden. 2015

Jung, Seung Min / Ju, Ji Hyeon / Park, Mi-Sun / Kwok, Seung-Ki / Park, Kyung-Su / Kim, Ho-Youn / Yim, Hyeon Woo / Park, Sung-Hwan. ·Division of Rheumatology, Department of Internal Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, South Korea. ·Int J Rheum Dis · Pubmed #25557144.

ABSTRACT: AIM: The aim of this study was to investigate the incidence of tuberculosis (TB) following anti-tumor necrosis factor (TNF) therapy in an intermediate TB burden area and to compare the risk between drugs and diseases. METHODS: The data were obtained from a nationwide database maintained by the Health Insurance Review and Assessment Service. The study population comprised of patients who were prescribed with TNF inhibitors from 2005 to 2009. TB cases were selected based on prescription of anti-TB medications. RESULTS: Of 8421 patients in the study population, 1729 patients with latent TB prophylaxis were identified and 102 patients developed TB. The incidence of TB was 1017 per 100 000 person-years. When divided into four groups according to the main diagnosis and using an ankylosing spondylitis group as a reference, the incidence of TB was highest in patients with inflammatory bowel disease (IBD) (incidence rate ratio [IRR] 5.97, 95% confidence interval [CI] 3.34-10.66), followed by patients with rheumatoid arthritis (IRR 1.02, 95% CI 0.57-1.83) and those with psoriatic arthritis (IRR 1.00, 95% CI 0.14-7.30). Comparison between drugs showed a significantly lower incidence of TB in patients treated with etanercept (reference), highest incidence in those treated with infliximab (IRR 6.8, 95% CI 3.74-12.37) and an intermediate incidence in patients treated with adalimumab (IRR 3.45, 95% CI 1.82-6.55). CONCLUSIONS: The difference in TB risk between TNF inhibitors was similar with countries of low TB burden. This study suggests that particular attention is required for patients treated with TNF monoclonal antibodies.

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