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대한류마티스학회> Journal of Rheumatic Diseases(구 대한류마티스학회지)> The TNF-NF-κB-DKK1 Axis Promoted Bone Formation in the Enthesis of Ankylosing Spondylitis

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

Sungsin Jo , Bora Nam , Young Lim Lee , Hyosun Park , Subin Weon , Sung-hoon Choi , Ye-soo Park , Tae-hwan Kim
  • : 대한류마티스학회
  • : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권4호
  • : 연속간행물
  • : 2021년 10월
  • : 216-224(9pages)
Journal of Rheumatic Diseases(구 대한류마티스학회지)

DOI


목차

INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSION
ACKNOWLEDGMENTS
CONFLICT OF INTEREST
AUTHOR CONTRIBUTIONS
REFERENCES

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초록 보기

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 (917.4 [615.3∼1,310.0] pg/mL vs. 826.2 [670.3∼927.8] pg/mL, p=0.043). 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-κB activation upregulates the DKK1 transcript level. While, NF-κB inhibitor led to downregulate DKK1 expression in the enthesis. Besides, DKK1 overexpression promoted bone formation in enthesis. Conclusion. TNF induced DKK1 expression in the enthesis through NF-κB activation. TNF-induced DKK1 expression may play a bone formation in the radiologic progression of ankylosing spondylitis. (J Rheum Dis 2021;28:216-224)

UCI(KEPA)

간행물정보

  • : 의약학분야  > 내과학
  • : KCI등재
  • :
  • : 계간
  • : 2093-940X
  • : 2233-4718
  • : 학술지
  • : 연속간행물
  • : 1994-2021
  • : 1401


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KCI등재

1Delineating the Risk of Lupus Nephritis: How Far Have We Come?

저자 : Jisoo Lee

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 173-175 (3 pages)

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KCI등재

2KOBIO, the First Web-based Korean Biologics Registry Operated With a Unified Platform Among Distinct Disease Entities

저자 : Jinhyun Kim , Jung Hee Koh , Sung Jae Choi , Chan Hong Jeon , Seung-ki Kwok , Seong-kyu Kim , Chan-bum Choi , Jaejoon Lee , Changhoon Lee , Eon Jeong Nam , Yong-beom Park , Shin-seok Lee , Tae-hwan Kim ,

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 176-182 (7 pages)

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The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment. (J Rheum Dis 2021;28:176-182)

KCI등재

3Epidemiologic and Etiological Features of Korean Patients With Behçet's Disease

저자 : Soo Hyun Choi , Do-young Kim

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 183-191 (9 pages)

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Behçet's disease (BD) is a multisystem disease in which environmental factors provoke an adverse immune response in patients with genetic susceptibility towards BD, subsequently leading to a cascade of dysregulated inflammation throughout the body. It is particularly prevalent in regions spanning the ancient Silk Road, including Korea, where the first known case of BD was reported in 1961. We summarize the history, epidemiology, and clinical presentation of BD in Korea, highlighting the clinical tendencies that are particularly seen in the Korean BD population as compared to European populations. Analysis of epidemiologic trends over the past three decades in Korea shows a decreasing prevalence of complete BD and a higher prevalence of intestinal BD. We also discuss the ever-evolving understanding of the pathogenesis of BD, noting the complex interplay among genetics, environment, and immunology. The HLA-B51 allele is the most significant known genetic risk factor in developing BD. We also discuss more recently studied associations between BD and immune factors such as IL-10, IL-23R-IL-12RB2, IL-1A-IL-1B, CCR1, ERAP1, and the GIMAP cluster, the last of which has been found to have an association with BD specifically in Korea. Environmental factors such as pollution and microbials are often the inciting event in developing BD, as they trigger an imbalanced immune response in genetically susceptible individuals, one that has been often found to exhibit an aberrant Th1/Th17 response. There would be value to further studying the pathogenesis and clinical characteristics of Korean BD. (J Rheum Dis 2021;28:183-191)

KCI등재

4Rheumatoid Hand Surgery in the Era of Biologic Therapy: A Rheumatologist-oriented Overview

저자 : Jin Woo Park , Ji Sup Hwang , Hyun Sik Gong

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 192-201 (10 pages)

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Rheumatoid arthritis (RA) can cause significant hand and wrist damage and dysfunction. The aim of medical treatment is to eradicate inflammation and prevent damage to joints and soft tissues. Advances in newer biological therapies over the last two decades have resulted in greater remission rates and lower disease activity status. Despite these improvements, surgical intervention is still indicated in cases of disability, irreversible deformities, and severe pain. However, there are large variations in the surgical rates of common rheumatoid hand procedures, which may indicate clinical uncertainty or disagreement between treating rheumatologists and hand surgeons. In this review, we provide a basic overview of common problems of the hand and wrist in RA patients. The target audience is rheumatologists for their better understanding of surgical options and for better informed patient consultation before referring to hand surgeons. (J Rheum Dis 2021;28:192-201)

KCI등재

5Safety of Tacrolimus in Autoimmune Disease: Results From Post-marketing Surveillance in South Korea

저자 : Wan-hee Yoo , Sang-il Lee , Tae-hwan Kim , Jung-joon Sung , Seung Min Kim , Fan Hua , Budiwan Sumarsono , Sung Hwan Park

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 202-215 (14 pages)

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Objective. Tacrolimus, a macrolide immunosuppressant, is approved in Korea for the treatment of rheumatoid arthritis (RA), lupus nephritis (LN) and myasthenia gravis (MG). We report three prospective post-marketing surveillance studies of tacrolimus conducted in South Korea in these indications. Methods. Studies were conducted according to South Korean Ministry of Food and Drug Safety requirements. Patients were followed up for the duration of the study (up to 4 years) or until treatment discontinuation. Occurrence and likely relationship with tacrolimus of adverse events (AEs), adverse drug reactions (ADRs; defined as AEs where causal relationship to tacrolimus could not be excluded) and serious AEs were recorded. Association of AEs with demographic and medical factors was evaluated by multivariable analysis. Results. The studies included 740 (RA), 307 (LN) and 104 (MG) patients. The incidence of AEs was 12.7% in RA (64.2% of AEs potentially related to tacrolimus), 20.9% (37.8% potentially related) in LN and 29.8% (56.8% potentially related) in MG. The incidence of ADRs was 8.4%, 9.8% and 20.2%, respectively. Serious AEs were reported in 0.7%, 7.2% and 8.7%, respectively. The most common AEs were abdominal pain (RA), pharyngitis (LN) and diarrhea (MG). Unexpected AEs occurred in 3.5% of patients with RA, 2.9% in LN and 8.7% in MG; no pattern of unexpected AEs was apparent. Multivariable analysis demonstrated that patients with comorbidity had higher probability of experiencing an AE in RA and MG studies. Conclusion. The incidence of AEs and the safety profile of tacrolimus in each indication was consistent with previous reports. (J Rheum Dis 2021;28:202-215)

KCI등재

6The TNF-NF-κB-DKK1 Axis Promoted Bone Formation in the Enthesis of Ankylosing Spondylitis

저자 : Sungsin Jo , Bora Nam , Young Lim Lee , Hyosun Park , Subin Weon , Sung-hoon Choi , Ye-soo Park , Tae-hwan Kim

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 216-224 (9 pages)

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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 (917.4 [615.3∼1,310.0] pg/mL vs. 826.2 [670.3∼927.8] pg/mL, p=0.043). 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-κB activation upregulates the DKK1 transcript level. While, NF-κB inhibitor led to downregulate DKK1 expression in the enthesis. Besides, DKK1 overexpression promoted bone formation in enthesis. Conclusion. TNF induced DKK1 expression in the enthesis through NF-κB activation. TNF-induced DKK1 expression may play a bone formation in the radiologic progression of ankylosing spondylitis. (J Rheum Dis 2021;28:216-224)

KCI등재

7J-shaped Relationship Between Chronic Kidney Disease and Serum Uric Acid Levels: A Cross-sectional Study on the Korean Population

저자 : Bon San Koo , Hye-jin Jeong , Chang-nam Son , Sang-hyon Kim , Gheun-ho Kim , Jae-bum Jun

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 225-233 (9 pages)

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Objective. Both hypouricemia and hyperuricemia are reportedly associated with reduced kidney function. This study investigated the association between uric acid levels and the risk of reduced renal function in men and women. Methods. We conducted a cross-sectional study using data from a government-funded health examinee cohort of a Korean genome and epidemiological study. A total of 172,970 participants (58,981 men, 113,989 women) aged 40∼79 years were included. A logistic regression test was performed, and the odds ratio (OR) and 95% confidence interval (CI) were calculated to examine the relationship between stratified uric acid levels and the frequency of chronic kidney disease. Results. As the uric acid level increased, the risk of reduced renal function increased. Moreover, for uric acid levels ≤2.0 mg/dL, the risk of reduced renal function was higher than that of the reference group. Among the total, man, and woman groups, a statistically significant association was observed in men (OR 1.71, 95% CI 0.945∼3.111, OR 5.003, 95% CI 1.405∼17.809, and OR 1.377, 95% CI 0.696∼2.724, respectively). Conclusion. The OR of reduced renal function according to uric acid levels formed a J-shaped curve in both genders. (J Rheum Dis 2021;28:225-233)

KCI등재

8Association of Serum Biomarkers With Pulmonary Involvement of Rheumatoid Arthritis Interstitial Lung Disease: From KORAIL Cohort Baseline Data

저자 : Jinyoung Moon , Jeong Seok Lee , Young Im Yoon , Sung Hae Chang , Yeon Ah Lee , You-jung Ha , Eun Ha Kang , Yong-beom Park , Hwa Jung Lee , Jung-yoon Choi , Eun Young Lee

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 234-241 (8 pages)

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Objective. The increase in mortality in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) is well known. However, there are few studies on serum markers that can evaluate acute exacerbation or prognosis in RA-ILD patients. The purpose of this study was to identify the association between biomarkers and lung lesions in patients with RA-ILD. Methods. We analyzed 153 patients with serum samples in a prospective, multicenter cohort of Korean RA-ILD patients. The serum levels of biomarkers, matrix metalloproteinase (MMP-7), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) were measured and correlated with forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the results of computed tomography (CT). CT results were interpreted semi-quantitatively according to the extent of lung lesions (grade 1, 0%∼25%; grade 2, 26%∼50%; grade 3, 51%∼75%; grade 4, 76%∼100%). Results. MMP-7, SP-D, and KL-6 were negatively correlated with FVC (MMP-7, r=-0.267, p=0.001; SP-D, r=-0.250, p=0.002; KL-6, r=-0.223, p=0.006) and DLCO (MMP-7, r=-0.404, p<0.001; SP-D, r=-0.286, p=0.001; KL-6, r=-0.226, p=0.007). In addition, MMP-7, SP-D, and KL-6 tended to increase with higher grades of lung lesions on CT (MMP-7, p=0.013; SP-D, p<0.001; KL-6, p<0.001). Conclusion. MMP-7, SP-D, and KL-6 can be used to evaluate the functional and anatomical status of lung involvement in the RA-ILD patients. (J Rheum Dis 2021;28:234-241)

KCI등재

9A Case of Overlap Syndrome of Systemic Sclerosis and Cryoglobulinemic Vasculitis With Central Nervous System Involvement

저자 : Youjin Jung , Eunyoung Emily Lee , Jina Yeo , Mi Hyeon Kim , Se Rim Choi , Yeong Wook Song

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 242-246 (5 pages)

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Mixed cryoglobulinemic vasculitis (CV) is occasionally caused by autoimmune diseases including systemic sclerosis. Multiorgan involvement such as skin, kidney, and peripheral nerve involvement is common in mixed CV. However, central nervous system (CNS) involvement is extremely rare. Here, we report a case of overlap syndrome of limited cutaneous systemic sclerosis and mixed cryoglobulinemic vasculitis with CNS involvement. The neurologic deficits and systemic symptoms improved promptly after steroid and cyclophosphamide therapy. (J Rheum Dis 2021;28:242-246)

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KCI등재

1Delineating the Risk of Lupus Nephritis: How Far Have We Come?

저자 : Jisoo Lee

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 173-175 (3 pages)

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KCI등재

2KOBIO, the First Web-based Korean Biologics Registry Operated With a Unified Platform Among Distinct Disease Entities

저자 : Jinhyun Kim , Jung Hee Koh , Sung Jae Choi , Chan Hong Jeon , Seung-ki Kwok , Seong-kyu Kim , Chan-bum Choi , Jaejoon Lee , Changhoon Lee , Eon Jeong Nam , Yong-beom Park , Shin-seok Lee , Tae-hwan Kim ,

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 176-182 (7 pages)

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The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment. (J Rheum Dis 2021;28:176-182)

KCI등재

3Epidemiologic and Etiological Features of Korean Patients With Behçet's Disease

저자 : Soo Hyun Choi , Do-young Kim

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 183-191 (9 pages)

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(기관인증 필요)

초록보기

Behçet's disease (BD) is a multisystem disease in which environmental factors provoke an adverse immune response in patients with genetic susceptibility towards BD, subsequently leading to a cascade of dysregulated inflammation throughout the body. It is particularly prevalent in regions spanning the ancient Silk Road, including Korea, where the first known case of BD was reported in 1961. We summarize the history, epidemiology, and clinical presentation of BD in Korea, highlighting the clinical tendencies that are particularly seen in the Korean BD population as compared to European populations. Analysis of epidemiologic trends over the past three decades in Korea shows a decreasing prevalence of complete BD and a higher prevalence of intestinal BD. We also discuss the ever-evolving understanding of the pathogenesis of BD, noting the complex interplay among genetics, environment, and immunology. The HLA-B51 allele is the most significant known genetic risk factor in developing BD. We also discuss more recently studied associations between BD and immune factors such as IL-10, IL-23R-IL-12RB2, IL-1A-IL-1B, CCR1, ERAP1, and the GIMAP cluster, the last of which has been found to have an association with BD specifically in Korea. Environmental factors such as pollution and microbials are often the inciting event in developing BD, as they trigger an imbalanced immune response in genetically susceptible individuals, one that has been often found to exhibit an aberrant Th1/Th17 response. There would be value to further studying the pathogenesis and clinical characteristics of Korean BD. (J Rheum Dis 2021;28:183-191)

KCI등재

4Rheumatoid Hand Surgery in the Era of Biologic Therapy: A Rheumatologist-oriented Overview

저자 : Jin Woo Park , Ji Sup Hwang , Hyun Sik Gong

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 192-201 (10 pages)

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Rheumatoid arthritis (RA) can cause significant hand and wrist damage and dysfunction. The aim of medical treatment is to eradicate inflammation and prevent damage to joints and soft tissues. Advances in newer biological therapies over the last two decades have resulted in greater remission rates and lower disease activity status. Despite these improvements, surgical intervention is still indicated in cases of disability, irreversible deformities, and severe pain. However, there are large variations in the surgical rates of common rheumatoid hand procedures, which may indicate clinical uncertainty or disagreement between treating rheumatologists and hand surgeons. In this review, we provide a basic overview of common problems of the hand and wrist in RA patients. The target audience is rheumatologists for their better understanding of surgical options and for better informed patient consultation before referring to hand surgeons. (J Rheum Dis 2021;28:192-201)

KCI등재

5Safety of Tacrolimus in Autoimmune Disease: Results From Post-marketing Surveillance in South Korea

저자 : Wan-hee Yoo , Sang-il Lee , Tae-hwan Kim , Jung-joon Sung , Seung Min Kim , Fan Hua , Budiwan Sumarsono , Sung Hwan Park

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 202-215 (14 pages)

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Objective. Tacrolimus, a macrolide immunosuppressant, is approved in Korea for the treatment of rheumatoid arthritis (RA), lupus nephritis (LN) and myasthenia gravis (MG). We report three prospective post-marketing surveillance studies of tacrolimus conducted in South Korea in these indications. Methods. Studies were conducted according to South Korean Ministry of Food and Drug Safety requirements. Patients were followed up for the duration of the study (up to 4 years) or until treatment discontinuation. Occurrence and likely relationship with tacrolimus of adverse events (AEs), adverse drug reactions (ADRs; defined as AEs where causal relationship to tacrolimus could not be excluded) and serious AEs were recorded. Association of AEs with demographic and medical factors was evaluated by multivariable analysis. Results. The studies included 740 (RA), 307 (LN) and 104 (MG) patients. The incidence of AEs was 12.7% in RA (64.2% of AEs potentially related to tacrolimus), 20.9% (37.8% potentially related) in LN and 29.8% (56.8% potentially related) in MG. The incidence of ADRs was 8.4%, 9.8% and 20.2%, respectively. Serious AEs were reported in 0.7%, 7.2% and 8.7%, respectively. The most common AEs were abdominal pain (RA), pharyngitis (LN) and diarrhea (MG). Unexpected AEs occurred in 3.5% of patients with RA, 2.9% in LN and 8.7% in MG; no pattern of unexpected AEs was apparent. Multivariable analysis demonstrated that patients with comorbidity had higher probability of experiencing an AE in RA and MG studies. Conclusion. The incidence of AEs and the safety profile of tacrolimus in each indication was consistent with previous reports. (J Rheum Dis 2021;28:202-215)

KCI등재

6The TNF-NF-κB-DKK1 Axis Promoted Bone Formation in the Enthesis of Ankylosing Spondylitis

저자 : Sungsin Jo , Bora Nam , Young Lim Lee , Hyosun Park , Subin Weon , Sung-hoon Choi , Ye-soo Park , Tae-hwan Kim

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 216-224 (9 pages)

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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 (917.4 [615.3∼1,310.0] pg/mL vs. 826.2 [670.3∼927.8] pg/mL, p=0.043). 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-κB activation upregulates the DKK1 transcript level. While, NF-κB inhibitor led to downregulate DKK1 expression in the enthesis. Besides, DKK1 overexpression promoted bone formation in enthesis. Conclusion. TNF induced DKK1 expression in the enthesis through NF-κB activation. TNF-induced DKK1 expression may play a bone formation in the radiologic progression of ankylosing spondylitis. (J Rheum Dis 2021;28:216-224)

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7J-shaped Relationship Between Chronic Kidney Disease and Serum Uric Acid Levels: A Cross-sectional Study on the Korean Population

저자 : Bon San Koo , Hye-jin Jeong , Chang-nam Son , Sang-hyon Kim , Gheun-ho Kim , Jae-bum Jun

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 225-233 (9 pages)

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Objective. Both hypouricemia and hyperuricemia are reportedly associated with reduced kidney function. This study investigated the association between uric acid levels and the risk of reduced renal function in men and women. Methods. We conducted a cross-sectional study using data from a government-funded health examinee cohort of a Korean genome and epidemiological study. A total of 172,970 participants (58,981 men, 113,989 women) aged 40∼79 years were included. A logistic regression test was performed, and the odds ratio (OR) and 95% confidence interval (CI) were calculated to examine the relationship between stratified uric acid levels and the frequency of chronic kidney disease. Results. As the uric acid level increased, the risk of reduced renal function increased. Moreover, for uric acid levels ≤2.0 mg/dL, the risk of reduced renal function was higher than that of the reference group. Among the total, man, and woman groups, a statistically significant association was observed in men (OR 1.71, 95% CI 0.945∼3.111, OR 5.003, 95% CI 1.405∼17.809, and OR 1.377, 95% CI 0.696∼2.724, respectively). Conclusion. The OR of reduced renal function according to uric acid levels formed a J-shaped curve in both genders. (J Rheum Dis 2021;28:225-233)

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8Association of Serum Biomarkers With Pulmonary Involvement of Rheumatoid Arthritis Interstitial Lung Disease: From KORAIL Cohort Baseline Data

저자 : Jinyoung Moon , Jeong Seok Lee , Young Im Yoon , Sung Hae Chang , Yeon Ah Lee , You-jung Ha , Eun Ha Kang , Yong-beom Park , Hwa Jung Lee , Jung-yoon Choi , Eun Young Lee

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 234-241 (8 pages)

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Objective. The increase in mortality in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) is well known. However, there are few studies on serum markers that can evaluate acute exacerbation or prognosis in RA-ILD patients. The purpose of this study was to identify the association between biomarkers and lung lesions in patients with RA-ILD. Methods. We analyzed 153 patients with serum samples in a prospective, multicenter cohort of Korean RA-ILD patients. The serum levels of biomarkers, matrix metalloproteinase (MMP-7), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) were measured and correlated with forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the results of computed tomography (CT). CT results were interpreted semi-quantitatively according to the extent of lung lesions (grade 1, 0%∼25%; grade 2, 26%∼50%; grade 3, 51%∼75%; grade 4, 76%∼100%). Results. MMP-7, SP-D, and KL-6 were negatively correlated with FVC (MMP-7, r=-0.267, p=0.001; SP-D, r=-0.250, p=0.002; KL-6, r=-0.223, p=0.006) and DLCO (MMP-7, r=-0.404, p<0.001; SP-D, r=-0.286, p=0.001; KL-6, r=-0.226, p=0.007). In addition, MMP-7, SP-D, and KL-6 tended to increase with higher grades of lung lesions on CT (MMP-7, p=0.013; SP-D, p<0.001; KL-6, p<0.001). Conclusion. MMP-7, SP-D, and KL-6 can be used to evaluate the functional and anatomical status of lung involvement in the RA-ILD patients. (J Rheum Dis 2021;28:234-241)

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9A Case of Overlap Syndrome of Systemic Sclerosis and Cryoglobulinemic Vasculitis With Central Nervous System Involvement

저자 : Youjin Jung , Eunyoung Emily Lee , Jina Yeo , Mi Hyeon Kim , Se Rim Choi , Yeong Wook Song

발행기관 : 대한류마티스학회 간행물 : Journal of Rheumatic Diseases(구 대한류마티스학회지) 28권 4호 발행 연도 : 2021 페이지 : pp. 242-246 (5 pages)

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Mixed cryoglobulinemic vasculitis (CV) is occasionally caused by autoimmune diseases including systemic sclerosis. Multiorgan involvement such as skin, kidney, and peripheral nerve involvement is common in mixed CV. However, central nervous system (CNS) involvement is extremely rare. Here, we report a case of overlap syndrome of limited cutaneous systemic sclerosis and mixed cryoglobulinemic vasculitis with CNS involvement. The neurologic deficits and systemic symptoms improved promptly after steroid and cyclophosphamide therapy. (J Rheum Dis 2021;28:242-246)

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