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3. Interleukin-37 Inhibits Interleukin-1β-Induced Articular Chondrocyte Apoptosis by Suppressing Reactive Oxygen Species.

Author

Kim, Seong-Kyu, Kim, Boyoung, Choe, Jung-Yoon, Kim, Ji-Won, and Park, Ki-Yeun

Subjects
CELL analysis, EXTRACELLULAR matrix, CELL cycle, REACTIVE oxygen species, CARTILAGE cells, CELL death
Abstract

Objective: Chondrocyte apoptosis has been considered a crucial mechanism that is responsible for cartilage destruction in osteoarthritis (OA). The mechanism of interleukin-37 (IL-37) on chondrocyte apoptosis has not been clearly determined in the pathogenesis of OA. Here, we explored the role of IL-37 in the regulation of cellular apoptosis in rat chondrocytes stimulated by IL-1β. Methods: Rat chondrocytes were used in in vitro study, and were stimulated with IL-1β (10 ng/mL) and/or recombinant IL-37 (rIL-37; 100 ng/mL) after cytotoxicity assessments using these cytokines were conducted. After rIL-37 treatment of chondrocytes stimulated with IL-1β, the cell proliferation assay, apoptosis assays, including expression of mitochondrial apoptosis-related markers, flow cytometry analysis of annexin V-FITC/propidium iodide (PI), cell cycle analysis, and Hoechst 33342 staining, and reactive oxygen species (ROS) measurement were used. Results: IL-1β induced expression of inflammatory cytokines and triggered degradation of the extracellular matrix of rat chondrocytes, but this effect was significantly attenuated by rIL-37 treatment. Enhanced ROS generation following IL-1β stimulation was reduced in a dose-dependent manner after stimulation with rIL-37. IL-1β induced pro-apoptotic markers and suppressed anti-apoptotic markers in rat chondrocytes. Flow cytometry using annexin V-FITC/PI revealed that IL-1β increased the apoptosis rate of rat chondrocytes, and that this effect was markedly reversed by treatment with rIL-37. Conclusions: IL-37 potently attenuated IL-1β-mediated apoptosis of rat chondrocytes by blocking ROS production. This study suggests that IL-37 can serve as a novel anti-cytokine therapy in OA by blocking chondrocyte apoptosis. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Anti-Inflammatory Effect of Atorvastatin and Rosuvastatin on Monosodium Urate-Induced Inflammation through IL-37/Smad3-Complex Activation in an In Vitro Study Using THP-1 Macrophages.

Author

Kim, Seong-Kyu, Choe, Jung-Yoon, Kim, Ji-Won, Park, Ki-Yeun, and Kim, Boyoung

Subjects
*INTERLEUKIN-37, *GENE expression, *POLYMERASE chain reaction, *REDUCTASE inhibitors, *CASPASES
Abstract

Objective: The pleiotropic effect of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) is responsible for potent defense against inflammatory response. This study evaluated the inhibitory effects of HMG-CoA reductase inhibitors on the monosodium urate (MSU)-induced inflammatory response through the regulation of interleukin-37 (IL-37) expression. Methods: Serum was collected from patients with gout (n = 40) and from healthy controls (n = 30). The mRNA and protein expression of the target molecules IL-1β, IL-37, caspase-1, and Smad3 were measured in THP-1 macrophages stimulated with MSU, atorvastatin, or rosuvastatin using a real-time quantitative polymerase chain reaction and Western blot assay. Transfection with IL-1β or Smad3 siRNA in THP-1 macrophages was used to verify the pharmaceutical effect of statins in uric-acid-induced inflammation. Results: Serum IL-37 levels in gout patients were significantly higher than in controls (p < 0.001) and was associated with the serum uric acid level (r = 0.382, p = 0.008). THP-1 cells stimulated with MSU markedly induced IL-37 mRNA expression and the transition of IL-37 from the cytoplasm to the nucleus. Recombinant IL-37 treatment dose-dependently inhibited activation of caspase-1 and IL-1β in MSU-induced inflammation. Atorvastatin and rosuvastatin attenuated caspase-1 activation and mature IL-1β expression but augmented translocation of IL-37 from the cytoplasm to the nucleus. Atorvastatin and rosuvastatin induced phosphorylation of Smad3 in THP-1 cells treated with MSU crystals. Statins potently attenuated translocation of IL-37 from the cytoplasm to the nucleus in THP-1 macrophages transfected with Smad3 siRNA compared to cells with negative control siRNA. Conclusions: This study revealed that statins inhibit the MSU-induced inflammatory response through phosphorylated Smad3-mediated IL-37 expression in THP-1 macrophages. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial

Author

Adams, Luthando, Ally, Mahmood M, du Plooy, Maria C, Louw, Ingrid C, Nayiager, Savithree, Nel, Christoffel B, Nel, Debra, Reuter, Helmuth, Soloman, Ahmed S, Spargo, Catherine E, Hall, Stephen, Rischmueller, Maureen, Sharma, Shunil D, Will, Robert K, Youssef, Peter P, Arroyo, Caroline, Baes, Rosario P, Dulos, Roger B, Hao, Llewellyn T, Lanzon, Allan E, Lichauco, Juan Javier T, Mangubat, Jill H, Ramiterre, Edgar B, Reyes, Bernadette Heizel M, Tan, Perry P, Choe, Jung-Yoon, Kang, Young Mo, Kwon, Seong Ryul, Lee, Sang-Heon, Lee, Shin-Seok, Yoo, Dae-Hyun, Lin, Hsiao-Yi, Luo, Shue-Fen, Tsai, Shih-Tzu, Tsai, Wen-Chan, Tseng, Jui-Cheng, Wei, Cheng-Chung C, Asavatanabodee, Paijit, Nantiruj, Kanokrat, Nilganuwong, Surasak, Uea-Areewongsa, Parichat, Majstorovic, Ljubinka Bozic, Bacic, Suada Mulic, Batalov, Anastas Z, Georgieva-Slavcheva, Gabriela, Mihailova, Mariyana, Nikolov, Nikolay G, Penev, Dimitar P, Spasov, Yuliy A, Stanimirova, Krasimira, Todorov, Stoyan, Toncheva, Antoaneta R, Yordanova, Nadezhda, Mosterova, Zdenka, Novosad, Libor, Prochazkova, Leona, Stehlikova, Helena, Stejfova, Zuzana, Kiseleva, Natalia, Pank, Lea, Savi, Triin, Alexandra, Balbir-Gurman, Amital, Howard, Mevorach, Dror, Rosner, Itzhak A, Mihailova, Anna, Stumbra-Stumberga, Evija, Basijokiene, Vida, Lietuvininkiene, Virginija, Unikiene, Dalia, Brzezicki, Jan, Dudek, Anna M, Glowacka-Kulesz, Maria B, Grabowicz-Wasko, Barbara, Hajduk-Kubacka, Sabina, Hilt, Joanna, Hrycaj, Pawel, Jeka, Slawomir, Kolasa, Renata, Krogulec, Marek, Mastalerz, Hanna, Olak-Popko, Anna, Owczarek, Elzbieta, Ruzga, Zofia, Walczak, Alina, Ancuta, Codrina I, Ancuta, Ioan, Balanescu, Andra R, Berghea, Florian, Bojin, Silvia, Arvunescu, Mihaela A Ianuli, Ionescu, Ruxandra M, Mociran, Eugenia, Pavel, Mariana, Rednic, Simona, Voie, Adriana, Zainea, Carmen M, Bugrova, Olga V, Demin, Alexander, Ershova, Olga B, Gavrisheva, Inna A, Krechikova, Diana G, Kuropatkin, Gennady V, Marusenko, Irina M, Menshikova, Irina V, Noskov, Sergey M, Rebrov, Andrey P, Smakotina, Svetlana A, Yakushin, Sergey S, Zhilyaev, Evgeny, Ramos, Juan Jose Amarelo, Garcia, Francisco Javier Blanco, Nebro, Antonio Fernandez, Esteban, Silvia Perez, Burson, Juan Miguel Sanchez, Sala, Raimon Sanmarti, Ataman, Sebnem, Hizmetli, Sami, Kuru, Omer, Douglas, Karen M, Emery, Paul, Moots, Robert J, Ong, Voon H, Sheeran, Thomas P, Faraawi, Rafat Y, Lessard, Clode, Mendoza, Carlos Abud, Avila-Armengol, Hilario Ernesto, Zapata, Francisco I Avila, Irazoque-Palazuelos, Fedra Consuelo, Cecena, Marco Antonio Maradiaga, Pacheco-Tena, Cesar F, Rizo-Rodriguez, Juan C, Rodriguez-Torres, Isaura M, Aelion, Jacob A, Caciolo, Barbara A, Calmes, James M, Chatpar, Prem, Dayal, Nimesh, De Jesus, Alex, Dikranian, Ara H, Diri, Erdal, Fairfax, Michael J, Fenton, Ira F, Fleischmann, Roy M, Gaylis, Norman B, George, Ronald L, Halter, Dale G, Hernandez, Paul, Hole, Susan A, Hou, Antony C, Huff, John P, Kafaja, Suzanne, Kennedy, Alastair C, Kenney, Howard, Kimmel, Steven C, Kirby, Brian S, Kivitz, Alan J, Legerton, Clarence W, Lindsey, Stephen M, Mallepalli, Jyothi R, Mathews, Steven D, Metyas, Samy K, Mizutani, Wesley T, Najam, Sabeen, Nascimento, Joao M, Pang, Shirley W, Patel, Rakesh C, Poiley, Jeffrey E, Ramirez, Carlos E, Reddy, Riteesha, Rehman, Qaiser, Schnitz, William M, Scoville, Craig D, Shergy, William J, Silverfield, Joel C, Singhal, Atul K, Smallwood-Sherrer, Yvonne R, Songcharoen, Suthin N, Stack, Michael T, Stohl, William, Su, Tien-I K, Udell, James, Waraich, Saleem, Weidmann, Charles E, Wei, Nathan, Wiesenhutter, Craig W, Winkler, Anne E, Zagar, Karen E, Berman, Alberto, Mysler, Eduardo F, Hidalgo, Rodolfo A Pardo, Venarotti, Horacio O, Sariego, Irmgadt Annelise Goecke, Calabresse, Renato E Jimenez, Ruiz-Tagle, Juan Ignacio Vargas, Vargas, Luis Fernando M Bellatin, Berrocal, Alfredo E, Portocarrero, Manuel Gustavo Leon, Jesus, Felix, Pena, Romero, Fleischmann, Roy, Mysler, Eduardo, Luo, Zhen, DeMasi, Ryan, Soma, Koshika, Zhang, Richard, Takiya, Liza, Tatulych, Svitlana, Mojcik, Christopher, Krishnaswami, Sriram, Menon, Sujatha, and Smolen, Josef S

Published
2017
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17. A non-interventional, post-marketing surveillance study evaluating the safety and effectiveness of biosimilar rituximab (CT-P10) during routine clinical practice in the Republic of Korea

Author

Jo, Jae-Cheol, primary, Jeon, Youngwoo, additional, Kim, DaJung, additional, Yang, Deok-Hwan, additional, Lee, Won Sik, additional, Choi, Yoon Seok, additional, Yi, Jun Ho, additional, Yoon, Dok Hyun, additional, Kong, Jee Hyun, additional, Choe, Jung-Yoon, additional, Kim, SungHyun, additional, Ahn, KeumYoung, additional, Park, TaeHong, additional, Ju, Hana, additional, Kwon, Soonbum, additional, and Cho, Seok-Goo, additional

Published
2023
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19. Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study

Author

Park, Min-Chan, Matsuno, Hiroaki, Kim, Jinseok, Park, Sung-Hwan, Lee, Sang-Heon, Park, Yong-Beom, Lee, Yun Jong, Lee, Sang-Il, Park, Won, Sheen, Dong Hyuk, Choe, Jung-Yoon, Choi, Chan-Bum, Hong, Seung-Jae, Suh, Chang-Hee, Lee, Shin-Seok, Cha, Hoon-Suk, Yoo, Bin, Hur, Jin-Wuk, Kim, Geun-Tae, Yoo, Wan-Hee, Baek, Han Joo, Shin, Kichul, Shim, Seung Cheol, Yang, Hyung-In, Kim, Hyun Ah, Park, Kyung-Su, Choi, In Ah, Lee, Jisoo, Tomomitsu, Masato, Shin, Seonghye, Lee, Jiyoon, and Song, Yeong Wook

Published
2019
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20. Lung function trajectory of rheumatoid arthritis–associated interstitial lung disease.

Author

Chang, Sung Hae, Lee, Ji Sung, Ha, You-Jung, Kim, Min Uk, Park, Chan Ho, Lee, Jeong Seok, Kim, Ji-Won, Chung, Sang Wan, Pyo, Jung Yoon, Lee, Sung Won, Kang, Eun Ha, Lee, Yeon-Ah, Park, Yong-Beom, Choe, Jung-Yoon, and Lee, Eun Young

Subjects
LUNG physiology, RESEARCH, RELATIVE medical risk, CLINICAL deterioration, SCIENTIFIC observation, CONFIDENCE intervals, INTERSTITIAL lung diseases, VITAL capacity (Respiration), RHEUMATOID arthritis, SYMPTOMS, PULMONARY function tests, RESEARCH funding, LONGITUDINAL method, DISEASE complications
Abstract

Objectives To explore the course of lung function and RA disease activity and predictive factors for deteriorating lung function in patients with RA-interstitial lung disease (ILD). Methods The Korean Rheumatoid Arthritis–Interstitial Lung Disease cohort is a multicentre, prospective observational cohort. Patients with RA-ILD were enrolled and followed up annually for 3 years for RA disease activity and ILD status assessment. Group-based modelling was used to cluster a similar predicted percentage of forced vital capacity (FVC%) patterns into trajectories. Results This study included 140 patients who underwent at least two pulmonary function tests. Four distinctive trajectories for predicted FVC% were 'improving' [ n  = 11 (7.9%)], 'stable' [ n  = 68 (38.4%)], 'slowly declining' [ n  = 54 (48.6%)] and 'rapidly declining' [ n  = 7 (5.0%)]. Most (77.7%) patients maintained or improved to low RA disease activity. The lung function trajectory was not comparable to the RA disease activity trajectory. Age ≥70 years [relative risk (RR) 10.8 (95% CI 1.30, 89.71)] and early RA diagnosed within the preceding 2 years [RR 10.1 (95% CI 1.22, 84.2)] were associated with increased risk for rapidly declining predicted FVC%. The risk for deterioration or mortality increased in patients with a simultaneous diagnosis of RA and ILD within 24 weeks [RR 9.18 (95% CI 2.05, 41.0)] and the extent of lung involvement [RR 3.28 (95% CI 1.12, 9.60)]. Conclusion Most patients with RA-ILD experienced stable or slowly declining lung function. In 5% of patients, predicted FVC% deteriorated rapidly, especially in older adults with early RA. The lung function trajectory was not comparable to the RA disease activity trajectory. [ABSTRACT FROM AUTHOR]

Published
2023
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30. Efficacy, Safety and Pharmacokinetics of Up to Two Courses of the Rituximab Biosimilar CT-P10 Versus Innovator Rituximab in Patients with Rheumatoid Arthritis: Results up to Week 72 of a Phase I Randomized Controlled Trial

Author

Yoo, Dae Hyun, Suh, Chang-Hee, Shim, Seung Cheol, Jeka, Slawomir, Molina, Francisco Fidencio Cons, Hrycaj, Pawel, Wiland, Piotr, Lee, Eun Young, Medina-Rodriguez, Francisco G., Shesternya, Pavel, Radominski, Sebastiao, Stanislav, Marina, Kovalenko, Volodymyr, Sheen, Dong Hyuk, Myasoutova, Leysan, Lim, Mie Jin, Choe, Jung-Yoon, Lee, Sang Joon, Lee, Sung Young, Kim, Sung Hwan, and Park, Won

Published
2017
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31. Efficacy and Safety of Switching from Innovator Rituximab to Biosimilar CT-P10 Compared with Continued Treatment with CT-P10: Results of a 56-Week Open-Label Study in Patients with Rheumatoid Arthritis

Author

Park, Won, Suh, Chang-Hee, Shim, Seung Cheol, Molina, Francisco Fidencio Cons, Jeka, Slawomir, Medina-Rodriguez, Francisco G., Hrycaj, Pawel, Wiland, Piotr, Lee, Eun Young, Shesternya, Pavel, Kovalenko, Volodymyr, Myasoutova, Leysan, Stanislav, Marina, Radominski, Sebastiao, Lim, Mie Jin, Choe, Jung-Yoon, Lee, Sang Joon, Lee, Sung Young, Kim, Sung Hwan, and Yoo, Dae Hyun

Published
2017
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32. Comparative effectiveness of treatment options after conventional DMARDs failure in rheumatoid arthritis

Author

Sung, Yoon-Kyoung, Cho, Soo-Kyung, Kim, Dam, Choi, Chan-Bum, Won, Soyoung, Bang, So-Young, Cha, Hoon-Suk, Choe, Jung-Yoon, Chung, Won Tae, Hong, Seung-Jae, Jun, Jae-Bum, Kim, Hyoun Ah, Kim, Jinseok, Kim, Seong-Kyu, Kim, Tae-Hwan, Lee, Hye-Soon, Lee, Jaejoon, Lee, Jisoo, Lee, Shin-Seok, Lee, Sung Won, Lee, Yeon-Ah, Nah, Seong-Su, Suh, Chang-Hee, Yoo, Dae-Hyun, Yoon, Bo Young, Bae, Sang Cheol, and For the BIOPSY and KORONA investigators

Published
2017
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34. Methotrexate, leflunomide and tacrolimus use and the progression of rheumatoid arthritis-associated interstitial lung disease

Author

Kim, Ji-Won, primary, Chung, Sang Wan, additional, Pyo, Jung Yoon, additional, Chang, Sung Hae, additional, Kim, Min Uk, additional, Park, Chan Ho, additional, Lee, Ji Sung, additional, Lee, Jeong Seok, additional, Ha, You-Jung, additional, Kang, Eun Ha, additional, Lee, Yeon-Ah, additional, Park, Yong-Beom, additional, Lee, Eun Young, additional, and Choe, Jung-Yoon, additional

Published
2022
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35. Safety and Effectiveness of Rituximab Biosimilar CT-P10 during Routine Clinical Practice: Final Analysis of a Post-Marketing Surveillance Study in the Republic of Korea

Author

Cho, Seok-Goo, primary, Jo, Jae-Cheol, additional, Jeon, Young-Woo, additional, Kim, Dajung, additional, Yang, Deok-Hwan, additional, Lee, Won Sik, additional, Choi, Yoon Seok, additional, Yi, Jun Ho, additional, Yoon, Dok Hyun, additional, Kong, Jee Hyun, additional, Choe, Jung-yoon, additional, Kim, Sung Hyun, additional, Ahn, Keum Young, additional, Park, TaeHong, additional, Park, Jeongah, additional, and Han, Sangeun, additional

Published
2022
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37. Safety, immunogenicity and efficacy after switching from reference infliximab to biosimilar SB2 compared with continuing reference infliximab and SB2 in patients with rheumatoid arthritis: results of a randomised, double-blind, phase III transition study

Author

Smolen, Josef S, Choe, Jung-Yoon, Prodanovic, Nenad, Niebrzydowski, Jaroslaw, Staykov, Ivan, Dokoupilova, Eva, Baranauskaite, Asta, Yatsyshyn, Roman, Mekic, Mevludin, Porawska, Wieslawa, Ciferska, Hana, Jedrychowicz-Rosiak, Krystyna, Zielinska, Agnieszka, Lee, Younju, and Rho, Young Hee

Published
2018
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38. Methotrexate, leflunomide and tacrolimus use and the progression of rheumatoid arthritis-associated interstitial lung disease.

Author

Kim, Ji-Won, Chung, Sang Wan, Pyo, Jung Yoon, Chang, Sung Hae, Kim, Min Uk, Park, Chan Ho, Lee, Ji Sung, Lee, Jeong Seok, Ha, You-Jung, Kang, Eun Ha, Lee, Yeon-Ah, Park, Yong-Beom, Lee, Eun Young, and Choe, Jung-Yoon

Subjects
DISEASE progression, CARBON monoxide, CONFIDENCE intervals, LEFLUNOMIDE, INTERSTITIAL lung diseases, METHOTREXATE, ANTIRHEUMATIC agents, VITAL capacity (Respiration), RHEUMATOID arthritis, DESCRIPTIVE statistics, RESEARCH funding, TACROLIMUS, LONGITUDINAL method
Abstract

Objective To examine the association between MTX, LEF and tacrolimus use and the progression of RA-associated interstitial lung disease (ILD). Methods The Korean RA-ILD cohort prospectively enrolled patients with RA-associated ILD at multiple centres from 2015 to 2018 and followed up with them for 3 years. ILD progression was defined by any of the followings: a decrease of ≥10% in forced vital capacity, a decrease of ≥15% in the diffusing capacity of the lung for carbon monoxide, or death from respiratory failure. Results Of 143 patients, 64 patients experienced ILD progression during a median follow-up period of 33 months. The use of MTX [adjusted hazard ratio (aHR), 1.06; 95% CI, 0.59, 1.89], LEF (aHR, 1.75; 95% CI, 0.88, 3.46) and tacrolimus (aHR, 0.94; 95% CI, 0.52, 1.72) did not increase the risk of ILD progression. However, the association between LEF use and the risk of ILD progression was significant in subgroups with poor lung function (aHR, 8.42; 95% CI, 2.61, 27.15). Older age, male sex, a shorter RA duration, higher RA disease activity and extensive disease at baseline were independently associated with ILD progression. Conclusion None of the three treatments increased the risk of RA-associated ILD progression, except for LEF, which increased the risk of ILD progression in patients with severe ILD. The appropriate use of conventional synthetic disease-modifying antirheumatic drugs considering RA disease activity and ILD severity would be important for the management of RA-associated ILD. [ABSTRACT FROM AUTHOR]

Published
2023
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43. Mapping health assessment questionnaire disability index (HAQ-DI) score, pain visual analog scale (VAS), and disease activity score in 28 joints (DAS28) onto the EuroQol-5D (EQ-5D) utility score with the KORean Observational study Network for Arthritis (KORONA) registry data

Author

Kim, Hye-Lin, Kim, Dam, Jang, Eun Jin, Lee, Min-Young, Song, Hyun Jin, Park, Sun-Young, Cho, Soo-Kyung, Sung, Yoon-Kyoung, Choi, Chan-Bum, Won, Soyoung, Bang, So-Young, Cha, Hoon-Suk, Choe, Jung-Yoon, Chung, Won Tae, Hong, Seung-Jae, Jun, Jae-Bum, Kim, Jinseok, Kim, Seong-Kyu, Kim, Tae-Hwan, Kim, Tae-Jong, Koh, Eunmi, Lee, Hwajeong, Lee, Hye-Soon, Lee, Jisoo, Lee, Shin-Seok, Lee, Sung Won, Park, Sung-Hoon, Shim, Seung-Cheol, Yoo, Dae-Hyun, Yoon, Bo Young, Bae, Sang-Cheol, and Lee, Eui-Kyung

Published
2016
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47. Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study

Author

Yin, Xianyong, Kim, Kwangwoo, Suetsugu, Hiroyuki, Bang, So-Young, Wen, Leilei, Koido, Masaru, Ha, Eunji, Liu, Lu, Sakamoto, Yuma, Jo, Sungsin, Leng, Rui-Xue, Otomo, Nao, Kwon, Young-Chang, Sheng, Yujun, Sugano, Nobuhiko, Hwang, Mi Yeong, Li, Weiran, Mukai, Masaya, Yoon, Kyungheon, Cai, Minglong, Ishigaki, Kazuyoshi, Chung, Won Tae, Huang, He, Takahashi, Daisuke, Lee, Shin-Seok, Wang, Mengwei, Karino, Kohei, Shim, Seung-Cheol, Zheng, Xiaodong, Miyamura, Tomoya, Kang, Young Mo, Ye, Dongqing, Nakamura, Junichi, Suh, Chang-Hee, Tang, Yuanjia, Motomura, Goro, Park, Yong-Beom, Ding, Huihua, Kuroda, Takeshi, Choe, Jung-Yoon, Li, Chengxu, Niiro, Hiroaki, Park, Youngho, Shen, Changbing, Miyamoto, Takeshi, Ahn, Ga-Young, Fei, Wenmin, Takeuchi, Tsutomu, Shin, Jung-Min, Li, Keke, Kawaguchi, Yasushi, Lee, Yeon-Kyung, Wang, Yong-Fei, Amano, Koichi, Park, Dae Jin, Yang, Wanling, Tada, Yoshifumi, Lau, Yu Lung, Yamaji, Ken, Zhu, Zhengwei, Shimizu, Masato, Atsumi, Takashi, Suzuki, Akari, Sumida, Takayuki, Okada, Yukinori, Matsuda, Koichi, Matsuo, Keitaro, Kochi, Yuta, Yamamoto, Kazuhiko, Ohmura, Koichiro, Kim, Tae-Hwan, Yang, Sen, Yamamoto, Takuaki, Kim, Bong-Jo, Shen, Nan, Ikegawa, Shiro, Lee, Hye-Soon, Zhang, Xuejun, Terao, Chikashi, Cui, Yong, Bae, Sang-Cheol, Japanese Research Committee on Idiopathic Osteonecrosis of the Femoral Head, Yin, Xianyong, Kim, Kwangwoo, Suetsugu, Hiroyuki, Bang, So-Young, Wen, Leilei, Koido, Masaru, Ha, Eunji, Liu, Lu, Sakamoto, Yuma, Jo, Sungsin, Leng, Rui-Xue, Otomo, Nao, Kwon, Young-Chang, Sheng, Yujun, Sugano, Nobuhiko, Hwang, Mi Yeong, Li, Weiran, Mukai, Masaya, Yoon, Kyungheon, Cai, Minglong, Ishigaki, Kazuyoshi, Chung, Won Tae, Huang, He, Takahashi, Daisuke, Lee, Shin-Seok, Wang, Mengwei, Karino, Kohei, Shim, Seung-Cheol, Zheng, Xiaodong, Miyamura, Tomoya, Kang, Young Mo, Ye, Dongqing, Nakamura, Junichi, Suh, Chang-Hee, Tang, Yuanjia, Motomura, Goro, Park, Yong-Beom, Ding, Huihua, Kuroda, Takeshi, Choe, Jung-Yoon, Li, Chengxu, Niiro, Hiroaki, Park, Youngho, Shen, Changbing, Miyamoto, Takeshi, Ahn, Ga-Young, Fei, Wenmin, Takeuchi, Tsutomu, Shin, Jung-Min, Li, Keke, Kawaguchi, Yasushi, Lee, Yeon-Kyung, Wang, Yong-Fei, Amano, Koichi, Park, Dae Jin, Yang, Wanling, Tada, Yoshifumi, Lau, Yu Lung, Yamaji, Ken, Zhu, Zhengwei, Shimizu, Masato, Atsumi, Takashi, Suzuki, Akari, Sumida, Takayuki, Okada, Yukinori, Matsuda, Koichi, Matsuo, Keitaro, Kochi, Yuta, Yamamoto, Kazuhiko, Ohmura, Koichiro, Kim, Tae-Hwan, Yang, Sen, Yamamoto, Takuaki, Kim, Bong-Jo, Shen, Nan, Ikegawa, Shiro, Lee, Hye-Soon, Zhang, Xuejun, Terao, Chikashi, Cui, Yong, Bae, Sang-Cheol, and Japanese Research Committee on Idiopathic Osteonecrosis of the Femoral Head

Abstract

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. We performed a transcriptome-wide association study (TWAS) using data from the latest genome-wide association meta-analysis of 208 370 East Asians and searched for candidate genes using TWAS and three data-driven computational approaches. Results TWAS identified 171 genes for SLE (p<1.0x10(-5)); 114 (66.7%) showed significance only in a single cell type; 127 (74.3%) were in SLE GWAS loci. TWAS identified a strong association between CD83 and SLE (p<7.7x10(-8)). Meta-analysis of genetic associations in the existing 208 370 East Asian and additional 1498 cases and 3330 controls found a novel single-variant association at rs72836542 (OR=1.11, p=4.5x10(-9)) around CD83. For the 110 SLE loci, we identified 276 gene candidates, including 104 genes at recently-identified SLE novel loci. We demonstrated in vitro that putative causal variant rs61759532 exhibited an allele-specific regulatory effect on ACAP1, and that presence of the SLE risk allele decreased ACAP1 expression. Conclusions Cell-level TWAS in six types of immune cells complemented SLE gene discovery and guided the identification of novel genetic associations. The gene findings shed biological insights into SLE genetic associations.

Published
2022

49. A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis

Author

Yoo, Dae Hyun, Suh, Chang-Hee, Shim, Seung Cheol, Jeka, Slawomir, Cons-Molina, Francisco Fidencio, Hrycaj, Pawel, Wiland, Piotr, Lee, Eun Young, Medina-Rodriguez, Francisco G, Shesternya, Pavel, Radominski, Sebastiao, Stanislav, Marina, Kovalenko, Volodymyr, Sheen, Dong Hyuk, Myasoutova, Leysan, Lim, Mie Jin, Choe, Jung-Yoon, Lee, Sang Joon, Lee, Sung Young, Kwon, Taek Sang, and Park, Won

Published
2017
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