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류마티스 관절염에서 제2형 콜라겐 반응 T세포와 활막 섬유 모세포의 상호 활성화
윤종현 ( Chong Hyeon Yoon ),박미경 ( Mi Kyung Park ),조미라 ( Mi La Cho ),고혁재 ( Hyeok Jae Ko ),박경수 ( Kyung Soo Park ),김완욱 ( Wan Uk Kim ),민준기 ( Jun Ki Min ),이상헌 ( Sang Heon Lee ),홍연식 ( Yeon Sik Hong ),박성환 ( Sun 대한류마티스학회 2004 대한류마티스학회지 Vol.11 No.1
Objective: To investigate the interaction between type II collagen (CII)-reactive T cell and fibroblast-like synoviocyte in rheumatoid arthritis (RA). Methods: Peripheral blood T cells from RA patients were cultured with bovine CII and analyzed by flow cytometry. After co-culture with CII-reactive T cells and fibroblast-like synoviocytes (FLS), the expression of cytokines (IL-15 and TNF-α from FLS, IFN-γ and IL-17 from CII-reactive T cells) were determined by ELISA and RT-PCR. Results: CII-reactive T cells expressed CD69, one of the early activation markers, and produced significant amount of IFN-γ, and proliferated. IL-15 and TNF-α expression from FLS were significantly elevated when co-culture with CII-reactive T cells and inhibited by physical interruption of cell-to-cell contact or anti-CD40 antibody. IFN-γ and IL-17 expression from CII-reactive T cells were also significantly elevated when co-culture with FLS and inhibited by anti-IL-15 monoclonal antibody. Conclusion: CII-reactive T cells can activate FLS to secret proinflammatoy cytokines and interactions between these two cells drive further activation of each other. These data suggest that CII-reactive T cell may play a important role in pathogenesis of RA.
윤종현 ( Chong Hyeon Yoon ),박경수 ( Kyung Soo Park ),최진정 ( Jin Jung Choi ),조미라 ( Mi La Cho ),민소연 ( So Youn Min ),김완욱 ( Wan Uk Kim ),민도준 ( Do June Min ),민준기 ( Jun Ki Min ),홍연식 ( Yeon Sik Hong ),박성환 ( Sung H 대한류마티스학회 2002 대한류마티스학회지 Vol.9 No.2
Objective: Infiltrating T cells and monocytes have been implicated in the pathogenesis of lupus nephritis (LN). Chemokines may play a key role in the recruitment of these cells. We investigated whether RANTES (regulated on activation normal T cell expressed and secreted), one of the CC chemokine family, may be involved in the pathogenesis of LN. Methods: We measured the levels of RANTES in sera and urine from 87 systemic lupus erythematosus (SLE) patients and 78 healthy controls using ELISA. Clinical and laboratory assessment including SLE disease activity index (SLEDAI) were performed at the time of sampling. Results: Serum RANTES levels were significantly higher in the patients with SLE than in healthy controls (115.0±5.6 vs. 91.5±4.0 pg/ml, p=0.001, mean±SEM). Serum RANTES levels correlated well with anti-dsDNA antibody titer (r=0.29, p<0.05) and inversely with serum complement C4 level (r=-0.28, p<0.05). Urinary RANTES/creatinine ratios were significantly higher in patients with nephritis than those without (3.4±0.4 vs. 2.2±0.3, p=0.004), while serum RANTES level was not different between patients with nephritis and those without. Moreover, urinary RANTES/creatinine ratio positively correlated with urine protein/creatinine ratio (r=0.41, p<0.001). Conclusions: Our results demonstrate that serum RANTES was elevated in patients with SLE and urinary excretion of RANTES was strongly associated with presence of nephritis. These data suggest that RANTES may be expressed in renal inflammatory sites and may participate in the pathogenesis of LN possibly by augmenting the recruitment of T cells and monocytes.
윤종현 ( Chong Hyeon Yoon ) 대한내과학회 2015 대한내과학회지 Vol.89 No.6
Ultrasonography (US) is a valuable imaging modality used to assess joint and periarticular abnormalities in patients with osteoarthritis (OA). US can detect articular cartilage damage, bony changes, joint effusion, synovitis, and adjacent soft tissue lesions. In addition, US facilitates the monitoring of disease progression and effects of treatments. US is a safe and accessible bedside procedure that can improve diagnosis and management of patients. The objective of this article was to describe the clinical applications of US for patients with OA. (Korean J Med 2015;89:616-619)
콜라겐 유도 관절염에서 콜라겐 항원 특이 $V{\beta}3$+CD4+T 세포의 선택적 증식
이재선,조미라,이정은,민소연,윤종현,김완욱,민준기,박성환,김호연,Lee, Jae-Seon,Cho, Mi-La,Lee, Jung-Eun,Min, So-Youn,Yoon, Chong-Hyeon,Kim, Wan-Uk,Min, Jun-Ki,Park, Sung-Hwan,Kim, Ho-Youn 대한면역학회 2005 Immune Network Vol.5 No.2
Background: Collagen-induced arthritis (CIA) in mice is animal model of autoimmune disease known as rheumatic arthritis in human. We investigated CII-specific CD4+ T cell receptor usage in CIA mice. Methods: In CIA model, draining lymph node (dLN) CD4+ T cells and splenocytes at $3^{rd},\;5^{th},\;8^{th}$ week, we investigated CII-specific T cell proliferation, production of IL-17, IFN-${\gamma}$, TNF-${\alpha}$, IL-4 and IL-10. And we also performed anti-CII IgG Ab measurements in serum level, TCRV ${\beta}$ usage and T cell clonality with RT-PCR-SSCP analysis. Also, we performed proliferative response against CII when CII-specific T cell subset is deleted. Results: CIA mice showed more increase in the serum level of anti-CII IgG than normal mice after induction of arthritis. And the level of anti-CII IgG2a in CIA mice was increased after $3^{rd}$ week after primary immunization, while anti-CII IgG1 was decreased. Draining LN CD4+ T cells have proliferated against CII stimulation at $3^{rd}$ week after $1^{st}$immunization. CD4+T cells derived from dLN of CIA mice produced proinflammatory cytokine IFN-${\gamma}$, IL-17 etc. Draining LN CD4 T cells of CIA presented higher proportion of CD4+V ${\beta}3$+subset compared to those of normal mice at $3^{rd}$ week after $1^{st}$ immunization, and they were increased in proportion by CII stimulation. Draining LN CD4+ T cells without TCRV ${\beta}3+/V{\beta}8.1/8.2+/V{\beta}$10b+cells were not responsive against CII stimulation. But, CII-reactive response of TCRV ${\beta}3-/V{\beta}8.1/8.2-/V{\beta}$10b- T cells was recovered when $V{\beta}3+$ T cells were added in culture. Conclusion: Our results indicate that CD4+$V{\beta}3+$ T cells are selectively expanded in dLN of CIA mice, and their recovery upon CII re-stimulation in vitro, as well as the production Th1-type cytokines, may play pivotal role in CIA pathogenesis.
고용량스테로이드 충격요법으로 치료된 전신홍반루프스 환자에서 동반된 심한 동서맥 1예
이진희 ( Jinhee Lee ),안효석 ( Hyo Suk Ahn ),윤종현 ( Chong Hyeon Yoon ) 대한내과학회 2019 대한내과학회지 Vol.94 No.2
Symptomatic sinus bradycardia in adults with systemic lupus erythematosus (SLE) is rare. Here, we report a case of severe sinus bradycardia requiring temporary cardiac pacing in a SLE patient successfully treated using methylprednisolone pulse therapy. (Korean J Med 2019;94:225-229)
베체트병 환자에서 혈중 Interleukin 15 농도 상승
박경수 ( Kyung Su Park ),민소연 ( So Youn Min ),조미라 ( Mi La Cho ),윤종현 ( Chong Hyeon Yoon ),김용주 ( Yong Ju Kim ),박종서 ( Jong Seo Park ),최진정 ( Jin Jung Choi ),김완욱 ( Wan Uk Kim ),홍연식 ( Youn Sik Hong ),민준기 ( Jun 대한류마티스학회 2002 대한류마티스학회지 Vol.9 No.2
Objective: To evaluate clinical significance of interleukin 15 (IL-15) in patients with Behcet`s disease (BD). Methods: Serum samples were obtained from 31 patients with BD and 29 healthy controls. BD patients were divided into active and inactive group according to the presence of clinical manifestations on the day of sampling. Serum levels of IL-15 and IL-8 were measured by sandwich enzyme-linked immunosorbent assay (ELISA). Results: Serum levels of IL-15 and IL-8 were significantly higher in BD patients than in healthy controls (117.2±26.2 pg/ml versus 51.8±15.4 pg/ml, p<0.01, 287.7±100.9 pg/ml versus 138.5±17.2 pg/ml, p<0.01, respectively). There was a significant correlation between serum levels of IL-15 and IL-8 (r(s)=0.653, p<0.01). BD patients with uveitis showed significantly elevated serum IL-15 levels compared with those without it (161.1±68.8 pg/ml versus 96.4±34.8 pg/ml, p<0.05). Serum levels of IL-15 and IL-8 tended to be higher in active group than in inactive group, but didn`t reach statistical significance. Conclusion: Serum level of IL-15 was elevated in patients with BD, especially those with uveitis, but it did not seem to be useful as a marker of disease activity in BD.
혈청음성 척추관절병증 환자의 발꿈치뼈 부착부병증에 대한 초음파 검사의 유용성
김해림 ( Hae Rim Kim ),홍지현 ( Ji Hyun Hong ),윤종현 ( Chong Hyeon Yoon ),이상헌 ( Sang Heon Lee ),박성환 ( Sung Hwan Park ),김호연 ( Ho Youn Kim ) 대한류마티스학회 2005 대한류마티스학회지 Vol.12 No.2
Objective: To determine the diagnostic value of ultrasonography (US) in detection of calcaneal enthesopathies and compare US findings with clinical examination and laboratory data in patients with seronegative spondyloarthropathy (SpA). Methods: We studied fifty six patients with SpA (ankylosing spondylitis 51; psoriatic arthritis 2; reactive arthritis 3). Gray scale US and power Doppler sonography (PDS) was performed in Achilles tendons and plantar fascia using a 40 mm, 12 MHz linear probe to detect tendon thickness, loss of normal fibrillar echogenecity, blurred tendon margin, calcification, fluid collection around tendon, bony erosion, enthesopathic spur, retrocalcaneal bursitis and increased vascularity. Clinical examination including Mander enthesis index (MEI) score, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were examined at the same time. Results: In 112 Achilles tendons, 72.3% showed abnormal US findings, as followings, increased tendon thickness 50.9%; loss of normal fibrillar echogenecity 32.1%; blurred tendon margin 24.1%; calcification 5.4%; fluid collection around tendon 17.7%; bony erosion 16%; enthesopathic spur 8.9%; retrocalcaneal bursitis 13.4%; and increased vascularity in power Doppler sonography (PDS) 14.2%. In 112 plantar aponeurosis, 59.8% showed abnormal US withenthesopathic spur 8.9%; retrocalcaneal bursitis 13.4%; and increased vascularity in power Doppler sonography (PDS) 14.2%. In 112 plantar aponeurosis, 59.8% showed abnormal US findings, as followings, increased tendon thickness 12.5%; loss of normal fibrillar echogenecity 50%; blurred tendon margin 30.3%; bony spur 2.7%; and increased vascularity in PDS 4.5%. PDS findings well correlated with findings of gray scale US. While 46% of symptomatic patients and 41.2% of patients with tenderness have abnormal X-ray findings, 69.4% of symptomatic patients and 73.8% of patients with tenderness have abnormal US findings. Patients with clinical symptoms, elevated CRP level and >1 MEI score showed increased vascularity in PDS. Conclusion: US is a simple and useful method in the detection of enthesopathies of SpA, even in patients without clinical symptom nor abnormal radiographic finding, and PDS combined with gray scale US is more sensitive tool which reflects the clinical examination.
이정민 ( Jeong Min Lee ),곽대훈 ( Dae Hun Kwack ),윤종현 ( Chong Hyeon Yoon ),최보미 ( Bomi Choi ),김영옥 ( Young Ok Kim ),김영수 ( Young Soo Kim ),윤선애 ( Sun Ae Yoon ) 대한내과학회 2017 대한내과학회지 Vol.92 No.3
본 증례는 치료를 받지 않고 지내던 전신홍반루푸스 환자에서 발생한 극심한 고칼슘혈증으로 혈액 투석 및 스테이로이드 치료로 호전된 예이다. 고칼슘혈증의 가장 흔한 원인은 부갑상선기능항진증 및 악성 종양에서 기인하는 부종양증후군이지만 전신홍반루푸스도 고칼슘혈증의 드문 원인 중 하나이므로 일반적인 원인들이 배제되면 전신홍반루푸스의 질병 활성도 및 관련 생화학 검사를 확인해 볼 것을 제시하는 바이다. Hypercalcemia is a common clinical problem. The most frequent causes of hypercalcemia include primary hyperparathyroidism and malignancy; systemic lupus erythematosus (SLE) is a very rare cause of hypercalcemia. Here we describe a case of symptomatic severe hypercalcemia, which developed during a lupus flare. After treatment with intravenous fluids, diuretics, pamidronate, and hemodialysis, calcium levels normalized and were maintained on low-dose prednisolone treatment. To the best of our knowledge, this is the first case of hypercalcemia in a patient with SLE in Korea. Clinicians should consider lupus as a differential diagnosis for patients with severe hypercalcemia. (Korean J Med 2017;92:300-302)
자가조혈모세포이식을 이용한 불응성 류마티스 관절염의 치료
민도준 ( Do June Min ),민창기 ( Chang Ki Min ),양동원 ( Dong Won Yang ),윤종현 ( Chong Hyeon Yoon ),김완욱 ( Wan Uk Kim ),이상헌 ( Sang Heon Lee ),김동욱 ( Dong Wook Kim ),이종욱 ( Jong Wook Lee ),조철수 ( Chul Soo Cho ),김호연 ( 대한류마티스학회 2002 대한류마티스학회지 Vol.9 No.1
Objective: To investigate the safety and efficacy of immunoablation and subsequent autologous hematopoietic stem cell transplantation (HSCT) in refractory rheumatoid arthritis (RA). Methods: Three patients with severe, refractory RA were treated. We mobilized autologous hematopoietic stem cells (HSCs) with cyclophosphamide (Cy) and granulocyte colony-stimulating factor. HSCs were collected and enriched ex vivo using CD34-positive immunoselection. Two different immunoablative conditioning regimens were employed; fludarabine-Cy-anti-thymoayte glonulin (ATG) in patients whose disease activity was transiently ameliorated in response to Cy used in stem cell mobilization, or fludarabine-busulfan-ATG in those who didn`t show any response to that. Results: Median time to engraftment with an absolute neutrophil count greater than 500/μl and nontransfused platelet count greater than 20,000/μl was 15 days (range 12-16) and 9 days (range 7-13), respectively. Regimen-related toxicity was minimal. Two patients were markedly improved at 2 or 3 months after HSCT, repectively. In another patient, disease activity was transiently subsided, but relapsed at 2 months after HSCT, which led to reinstitution of anti-rheumatic medications. This resulted in subsequent marked improvement of disease activity whereas her disease had been refractory to these medications. Conclusions: These results underscore the feasibility and potential efficacy of intensive immunosuppression followed by autologous HSCT for treatment of refractory rheumatoid arthritis. The durability of remission remains to be clarified.