전신성 홍반성 루푸스에서 IL-1α에 의한 항혈관내피세포항체 결합능의 증가

홍연식 ( Yeon Sik Hong ),김완욱 ( Wan Uk Kim ),민준기 ( Jun Ki Min ),박성환 ( Sung Hwan Park ),이상헌 ( Sang Heon Lee ),조철수 ( Chul Soo Cho ),김호연 ( Ho Youn Kim ) 대한류마티스학회 1998 대한류마티스학회지 Vol.5 No.1

저자들은 사람의 제대정맥 내피세포를 이용하여 전신성 홍반성 루푸스(SLE) 환자 혈청에서 항혈관내피세포항체(aECA)를 효소면역법으로 측정하여 aECA의 빈도를 알아보고 aECA가 혈관병변과 관련 있는 임상양상 및 항 cardiolipin 항체(aCL)와 어떤 연관성이 있는지를 조사하고, 또한 cytokine(IL-1α, TNF-α)으로 자극하여 혈관 내피세포를 활성화시킨 후 aECA와 결합하는 정도를 자극전과 비교 분석함으로써 aECA가 혈관 내피세포와 결합하는데 있어서의 cytokine의 역할을 규명하고자 하였다. 92명의 SLE 환자에서 IgG-aECA 양성률은 33.7%였고 그 평균역가는 19.38±20.74U/ml로 정상 대조군에 비해 유의한 증가를 보였다(P<0.05). IgG-aECA와 IgG-aCL의 혈청역가 사이에는 상관관계가 없었다. IgG-aECA 양성 환자에서 수지혈관염 및 레이노 현상의 빈도가 높았으며 이들 증상이 있는 환자들의 IgG-aECA 평균역가는 증상이 없는 환자보다 유의하게 높았다(P<0.05). 내피세포를 IL-1α로 자극한 후 60명의 환자에서 IgG-aECA 평균역가는 자극전에 비해 유의한 증가를 보였으나(P<0.0001), TNF-α로 자극후 IgG-aECA 역가의 변화는 유의한 차이가 없었다. IL-1α로 자극한 후 IgG-aECA 역가는 수지혈관염, 레이노현상, 신질환, 혈전증, 신경 정신과적 증상과 허혈성 골괴사가 있는 환자에서 자극전에 비해 의의있게 증가하였고 TNF-α로 자극시에는 자극전과 차이가 없었다. 자극전 aECA 양성 환자는 28명(46.7%)이었고 IL-1α 자극 후 41명(68.3%)으로 증가하였으며, TNF-α 자극 후에는 29명(48.3%)으로 큰 차이가 없었다. 이러한 사실을 종합해 볼때 전신성 홍반성 루푸스에서 IgG-aECA의 존재 및 IL-1α를 매개로 하는 IgG-aECA 결합능의 증가는 혈관손상의 한 요소로 작용하여 임상 증상 발현에 중요한 역할을 할 것으로 생각된다. Systemic lupus erythematosus(SLE) is a multiorgan disease which is associated with the occurrence of immune vascular damage. Antiendothelial cell antibodies(aECA) have been demonstrated in patients with SLE, and their presence could be related to vascular injury. Endothelial cell(EC) in vasculitic lesions of patients with SLE show evidence of activation. In vitro treatment of EC with cytokines can produce a pattern of activation such as the increased expression of surface molecules. Activation of EC was shown to influence the interaction between aECA and endothelial surface. The authors, therefore, examined the prevalence of IgG aECA and investigated the association of aECA with clinical findings and anticardiolipin antibodies(aCL). We also investigated the role of cytokine in binding of IgG-aECA to EC in patients with SLE. Sera from 92 patients with SLE and 20 healthy controls were assayed for IgG-aECA by cellular ELISA method using cultured human umbilical vein endothelial cell (HUVEC) and IgG-aCL by ELISA method, and We also examined the binding of IgG-aECA to EC activated with IL-1α or TNF-α in sera from 60 patients with SLE. IgG-aECA was detected in the serum of 31 out of 92 patients(33.7%). The mean serum titers of IgG-aECA were significantly higher in SLE than in healthy controls(19.38 U/ml vs 8.79 U/ml, P<0.05). There was no correlation between serum titers of IgG-aECA and IgG-aCL(r=-0.0265). The mean serum titers of IgG-aECA in patients with digital vasculitis or Raynaud`s phenomenon were significantly increased in comparison with patients without these manifestations(35.28 U/ml vs 18.16 U/ml, P<0.05. 27.18 U/ml vs 15.24 U/ml, P<0.05 respectively). The mean serum titers of IgG-aECA in 60 patients were significantly increased (P<0.0001) following the stimulation with IL-1α as compared with unstimulated EC, but those of IgG-aECA were not increased following the stimulation with TNF-α. The IgG-aECA binding reactivity to IL-1α stimulated EC was significantly higher in patients with digital vasculitis, Raynaud`s phenomenon, renal disorder, thrombosis, neuropsychiatric manifestation and avascular necrosis as compared with unstimulated EC. IgG-aECA was detected in 28 of the 60 patients(46.7%). Its frequency was increased following the stimulation with IL-1α(68.3%), but there was no significant difference in frequency following the stimulation with TNF-α(48.3%). These data suggest that presence of IgG-aECA and enhanced binding of IgG-aECA to EC induced by IL-1α can play an important role in the occurrence of clinical manifestations associated with vascular damage in SLE.

류마티스 관절염 환자에서 제2형 콜라겐의 치료효과

홍연식 ( Yeon Sik Hong ),김완욱 ( Wan Uk Kim ),이신석 ( Shin Seok Lee ),주영실 ( Yeong Sil Zoo ),민준기 ( Jun Ki Min ),박성환 ( Sung Hwan Park ),이상헌 ( Sang Heon Lee ),조철수 ( Chul Soo Cho ),김호연 ( Ho Youn Kim ) 대한류마티스학회 1999 대한류마티스학회지 Vol.6 No.2

연구목적: 류마티스 관절염 환자를 대상으로 CII을 경구 투여하여 CII의 치료효과와 안정성을 평가하고자 하였다. 대상 및 방법: RA 환자를 무작위로 2군(콜라겐 투여군 25명, 대조군 20명)으로 나누어 bovine CII을 하루에 100μg 3개월 동안 복용하고 1, 2, 3개월 후에 효과를 평가하였다. 반응 여부는 임상증상 호전에 관한 ACR 기준, Paulus 기준 및 부종과 동통관절수가 30% 이상 호전되었을 때 반응했다고 평가하고 시험기간 중 어느 때라도 기준을 만족하면 반응군이라 하고 전혀 반응을 보이지 않으면 비반응군이라 하였다. 결과: Paulus 기준을 적용했을 때 위약 투여군은 10%, CII 투여군은 40%가 반응하여 유의한 (p=0.04) 호전을 보였고, 환자 활동 및 상태 지표에 관한 평가(MHAQ)는 CII 투여군에서 3개월 후 유의한 감소를 보였다. 종창 몇 압통 관절수, 환자와 의사가 평가하는 VAS는 CII 투여군과 위약 투여군 사이에 통계적인 유의성은 없었다. 두 군 모두에서 약제에 의한 위중한 부작용은 없었으며 CII 투여군에서 투여전에 비해 투약 3개월 후 혈청 항 2형 콜라겐 항체의 의미있는 감소를 보였다. 결론: 저자들의 연구는 CII의 경구투여가 류마티스 관절염 치료에 효과적이며 안전한 치료법임을 보여준다. 혈청 항 2형 콜라겐 항체가 CII의 경구투여에 의해 감소된다는 사실은 CII의 경구투여에 의해 자가 항체 생성의 면역학적 관용이 유발될 수 있음을 시사한다. Objective: To investigate the efficacy and safety of oral bovine type II collagen(CII) in the treatment of rheumatoid arthritis(RA). Methods: Forty-five patients with active RA were enrolled and randomized to receive placebo or oral CII for 3 months. Efficacy parameters were assessed monthly. Cumulative response rates(percentages of patients meeting the criteria for response at anytime during the study) were analyzed utilizing 3 set of composite criteria: Paulus criteria, ACR criteria for improvement in RA, and a requirement for≥30% reduction in both swollen and tender joint counts. Results: The CII-treated group(n=25) showed significant higher response rate by the Paulus criteria compared to placebo group(n=20) (p=0.04), and MHAQ scores between baseline and 3 months of treatment were also significantly decreased in the CII-treated group(p<0.05). However, there were no significant differences in tender and swollen joint count, and physician and patient global scores between CII-treated and placebo groups. Only one patient treated with CII had a urticarica 1 week after administration, but no serious side effects were found in the two groups. Patients treated with CII(n=15) showed the decreased levels of circulating IgG antibodies to bovine CII 3 months after treatment(p=0.02), whereas significant changes of IgG antibodies to CII were not found in placebo group(n=12). Conclusion: Oral administration of CII was safe and effective for the treatment of rheumatoid arthritis. The finding that serum IgG antibodies to bovine CII was decreased in patients who treated with CII suggest that autoimmune response to CII could be decreased by repetitive administration of CII.

Acroosteolysis가 동반된 Sjogren`s 증후군

홍연식 ( Yeon Sik Hong ),양형인 ( Hyung In Yang ),박성환 ( Sung Hwan Park ),이상헌 ( Sang Heon Lee ),조철수 ( Chul Soo Cho ),김호연 ( Ho Youn Kim ) 대한류마티스학회 1996 대한류마티스학회지 Vol.3 No.1

Acroosteolysis (AOL) refers to a destructive process involving distal phalangeal shaft while the tuft and base are preserved. It can be a manifestation of various diseases, such as scleroderma, Raynaud`s disease, rheumatoid vasculitis, psoriasis, renal osteodystrophy and leprosy. Occupational exposure to polyvinyl chloride polymers, thermal injury, and repetitive mechanical injury can also cause this problem. Although the exact pathogenesis of AOL is uncertain, a unifying theme of vascular and mechanical injury is presented. Recently, we experienced a 32-year-old woman complained of xerophthalmia, zerostomia and polyarthralgia which was diagnosed as Sjogren syndrome associated with acroosteolysis. After administration of prednisolone, cyclophosphamide and oral bromhexine, subsidence of her symptoms was observed. We report this case with a review of relevant literature.

세무대리인의 의사결정에 있어서 인구통계적 요인의 영향

홍정화(Hong, Jung Hwa),김연식(Kim, Yeon Sig) 대한경영학회 2004 大韓經營學會誌 Vol.17 No.1

전신성 홍반성 루푸스에 병발한 Aspergillosis 2예

김현수 ( Hyun Su Kim ),홍연식 ( Yeon Sik Hong ),배상수 ( Sang Su Pae ),김완욱 ( Wan Uk Kim ),민준기 ( Jun Ki Min ),이상헌 ( Sang Heon Lee ),박성환 ( Seong Whan Park ),조철수 ( Chul Soo Cho ),김호연 ( Ho Youn Kim ) 대한류마티스학회 1999 대한류마티스학회지 Vol.6 No.3

Invasive infections with Aspergillus species may occur in patients with severe immune deficits and have been described rarely in systemic lupus erythematosus. We present two cases of pulmonary aspergillosis in steroid-treated systemic lupus erythematosus(SLE). Both patients had active SLE treated with high dose corticosteroids and prescribed with broad spectrum antibiotics. One patient had combined infection with pulmonary tuberculosis and the other present granulocytopenia. The diagnosis was delayed because symptoms and radiologic findings were confused with lupus pneumonitis and bacterial infections. This was similar to those reported previously. Diagnosis was confirmed by identification of the typical septated hyphae within tissue. We prescribed high dose amphotericin B to both patients. But one died with sepsis. Aspergillosis should be suspected in patients with active SLE who are immunocompromised and sustain concomitant bacterial infections. More aggressive diagnostic investigation and treatment may be needed to improve poor prognosis.

제 50 차 대한내과학회 추계학술대회 초록집 : 전신성 홍반성 루푸스에 병발한 Aspergillosis 2 예

민준기(Jun Ki Min),홍연식(Yeon Sik Hong),이상헌(Sang Heon Lee),박성환(Sung Hwan Park),조철수(Chul Soo Cho),김현수,김호연,김완욱 대한내과학회 1998 대한내과학회 추계학술대회 Vol.55 No.-

Sjogren 증후군 환자에서 발생한 재발성 다발성 연골염

이관형 ( Kwan Hyong Lee ),홍연식 ( Yeon Sik Hong ),강형주 ( Hyong Ju Kang ),김세희 ( Se Hee Kim ),김명철 ( Myoung Cheol Kim ),조철수 ( Chul Soo Cho ),김호연 ( Ho Youn Kim ),김기준 ( Ki Jun Kim ) 대한류마티스학회 2001 대한류마티스학회지 Vol.8 No.3

Relapsing polychondritis is a rare multisystem rheumatic disease, characterized by recurrent and potentially destructive inflammatory lesions of cartilaginous structures. All types of cartilage & other proteoglycan-rich structures may be involved, resulting in auricular chondritis, laryngotracheal chondritis, ocular symptoms, vasculitis, cardiac abnormalities, skin lesions and glomerulonephritis. The disease may be associated with another connective tissue and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, Sjogren`s syndrome and systemic vasculitis. We experienced a 69-year-old female patient who had been previously diagnosed as Sjogren`s syndrome, presenting respiratory tract involvement, episcleritis, auricular chondritis and vestibular dysfunction.

류마티스관절염 환자의 활액 세포에서 IL-17과 $IL-1{\beta}$에 의한 IL-23p19의 발현 증가

조미라,허유정,오혜좌,강창민,이선영,홍연식,김호연,Cho, Mi-La,Heo, Yu-Jung,Oh, Hye-Jwa,Kang, Chang-Min,Lee, Seon-Yeong,Hong, Yeon-Sik,Kim, Ho-Youn 대한면역학회 2008 Immune Network Vol.8 No.1

Interleukin-23 (IL-23) is a novel pro-inflammatory cytokine which has been implicated to play a pathogenic role in rheumatoid arthritis (RA). This study was undertaken to investigate the IL-23 inductive activity of the proinflammatory cytokine IL-17, $IL-1{\beta}$ and tumor necrosis factor (TNF-${\alpha}$) in RA synovial fluid mononuclear cells (SFMC). Expression of IL-23p19, IL-17, $IL-1{\beta}$ and TNF-${\alpha}$ in joint was examined by immunohistochemistry (IHC) of patients with RA and osteoarthritis (OA). The effects of IL-17 and $IL-1{\beta}$ on expression of IL-23p19 in human SFMC from RA patients were determined by reverse transcriptase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-23p19 was expressed in the RA fibroblast like synoviocyte (FLS), but not from OA FLS. Similar to the protein expression, IL-23p19 mRNA could be detected by RT-PCR in RA SFMC. IL-17 and $IL-1{\beta}$ could induce RA SFMC to produce the IL-23p19. The effects of IL-17 were much stronger than $IL-1{\beta}$ or TNF-${\alpha}$. These responses were observed in a doseresponsive manner. In addition, IL-17 or $IL-1{\beta}$ neutralizing antibody down-regulated the expression of IL-23p19 induced by LPS in RA-SFMC. Our results demonstrate that IL-23p19 is overexpressed in RA synovium and IL-17 and $IL-1{\beta}$ appears to upregulate the expression of IL-23p19 in RA-SFMC.

Comparision of Bacterial Organism in Bacteremia Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis in Korea

민준기 ( Jun Ki Min ),유진홍 ( Jin Hong Yoo ),민도준 ( Do June Min ),김완욱 ( Wan Uk Kim ),김영옥 ( Young Ok Kim ),홍연식 ( Yeon Sik Hong ),이상헌 ( Sang Heon Lee ),박성환 ( Sung Hwan Park ),조철수 ( Chul Soo Cho ),김호연 ( Ho You 대한내과학회 1999 대한내과학회 추계학술대회 Vol.57 No.-

염증성 근육병증에 동반된 폐침범의 임상적 특징

김현숙 ( Hyun Sook Kim ),서수홍 ( Soo Hong Seo ),허지안 ( Ji An Hur ),곽승기 ( Seung Ki Kwok ),주지현 ( Ji Hyeon Ju ),윤종현 ( Chong Hyeon Yoon ),김완욱 ( Wan Uk Kim ),홍연식 ( Yeon Sik Hong ),조철수 ( Chul Soo Cho ),김호연 ( Ho Y 대한류마티스학회 2007 대한류마티스학회지 Vol.14 No.1

Objective: To investigate the clinical manifestation and prognostic factors of interstitial lung disease (ILD) in Korean patients with idiopathic inflammatory myopathies include with polymyositis (PM) and dermatomyositis (DM). Methods: Clinical and laboratory data of 110 patients with PM/DM in our rheumatology clinic were investigated. Clinical data including history, medication, pulmonary function tests (PFT) findings, radiologic findings, and labaratory findings were obtained from medical records at the first diagnosis of ILD with PM/DM. ILD was diagnosed on the basis of the imaging abnormalities defined above on definite findings of chest X-rays and high resolution computed tomography (HRCT), restrictive changes on PFT with respiratory symptoms. During the course of treatment, we assessed chest radiograph and HRCT findings. Results: Forty-two PM/DM patients (38.2%) developed ILD. Anti-extracellular nuclear antigen (ENA) antibody, anti-Jo-1 antibody and ground glass opacity in HRCT were significantly high in PM-ILD. However honeycoomb appearance (53%:22%) and fibrosis (41%:6%) in HRCT were significantly high in DM-ILD. Interest in aspects of prognosis including initial steroid treatment response in HRCT were favorable in PM-ILD. There were statistically significant association between normal level of CPK and usual interstitial pneumonia (UIP) pattern in HRCT in DM-ILD. Such cases had resistance to steroid therapy. Overall interval between steroid and immunosuppressant therapy was significantly shorter in those with DM-ILD. Conclusion: The clinical manifestations between PM-ILD and DM-ILD in Korean patients were not significant different from those of other populations. DM-ILD is more refractory to steroid treatment, expecting in poor prognosis compared with PM-ILD. So immediate intensive immunosuppressive therapy should be considered in DM-ILD.