한국인에서 류마토이드 관절염과 제 2 형 조직적합항원과의 연관성에 관한 연구

유대현(Dae Hyun Yoo),서정대(Jeong Dai Suh),배상철(Sang Cheol Bae),김성윤(Seong Yoon Kim),김목현(Mok Hyun Kim),김신규(Thin Kyou Kim),주경빈(Kyung Bin Joo) 대한내과학회 1991 대한내과학회지 Vol.40 No.5

N/A Rheumatoid arthritis is a chronic inflammatory disease characterized as destructive polyarthritis and has evidence of immunogenetic and environmental elements in its etiologic factors. Many studies document that one of the key genetic elements is closely linked to the class II major histocompatibility complex located in chromosome 6. Although it is not. known precisely how HLA genes contribute to disease susceptibility, many studies document a close association between rheumatoid arthritis and the specific histocompatibility marker, HLA-DR4. However, studies of HLA-DR4 in disease severity have yielded conflictiing results. Association between HLA- DR4 and the rheumatoid factor, earlier age of onset, increased general disease severity and more erosive radiographic changes have been reported, but these associations have not been confirmed in other studies. In addition, there has been no report regarding the association between rheumatoid arthritis and class II MHC in Koreans. Therefore this is the first epidemiologic study regarding the association between rheumatoid arthritis and class II MHC. The disrtibution of class II major histocompatibility complex and association between HLA- DR4 and disease severity were analyzed in 206 Korean patients with rheumatoid arthritis in this study. The results were as follows: 1) HLA-DR4 was associated with rheumatoid arthritis in 61.6% of the patients studied. The relative risk and etiologic fraction of HLA-DR4 were 2.47 and 0.367, respectively. HLA-DR1 was positive in 11.1% and the etiologic fraction of HLA-DR1 was 0.008. Therefore HLA-DR4 was associated strongly with rheumatoid arthritis in Koreans, similar to other ethnic populations, but HLA-DR1 was not associated with rheumatoid arthritis in Koreans. 2) HLA-DR2 was positive in 19.9% and the preventive fraction of HLA-DR2 was 0.205. HLA-DR7 was positive in 4.3% and the preventive fraction of HLA- DR7 was 0.011. Hence HLA-DR2 was the most preventive class II MHC against the development of rheumatoid arthritis in this study. 3) HLA-Dgw3 was positive in 62.1% and the relative risk of HLA-DQw3 was 1.65, HLA-DQw7, which was known as HLA-DQw3.1, was positive in 20.5% and HLA-DR4 Dgw7 haplotype was positive in 15% of the total number of patients. 4) HLA-DR4 was significantly associated with a more advanced ARA anatomical grade and more severe radiographic changes, including bony erosion, joint space, narrowing and total radiographic score. 5) The rheumatoid facor was positive in 84.3% of the HLA-DR4 positive patients and positive in 82.3% of the HLA-DR4 negative patients. HLA-DR4 v as positive in 62.2% of the 172 seropositive patients and positive in 58.8% of the 34 seronegative patients. Therefore HLA-DR4 was not associated significantly with the presence of a rheumatoid factor in this study. 6) HLA-DR4 was not associated significantly with joint count (Ritchie index), ARA functional class, ESR, C-reactive protein or other demographic data. HLA-DR4 was not associated significantly with the positive rate of ANA, cryoglobulin. 7) Homozygous HLA-DR4 patients were 31 out of 127 DR4-positive patients and showed more advanced ARA anatomical stage and radiographic changes than heterozygous DR4 patients, but the difference was statistically insignificant. In summary, HLA-DR4 was significantly associated with rheumatoid arthritis in Koreans, similar to other ethnic populations, Also HLA-DR4 was significantly associated with more destructive arthritis, but not associated with rheumatoid factor positivity and the parameters representing disease activity of rheumatoid arthritis.

류마티스 관절염에 대한 한약의 면역학적 연구동향

최도영,이재동,백용현,이송실,유명철,한정수,양형인,박상도,유미현,박은경,박동석,Choi, Do-young,Lee, Jae-dong,Back, Yong-hyeon,Lee, Song-shil,Yoo, Myung-chul,Han, Chung-soo,Yang, Hyung-in,Park, Sang-do,Ryu, Mi-hyun,Park, Eun-kyung,Park, 대한침구의학회 2004 대한침구의학회지 Vol.21 No.4

Objective : Rheumatoid arthritis is an autoimmune disease that pathogenesis is not fully understood and one of the most intractable musculoskeletal diseases. The concern in the immunopathogenesis of rheumatoid arthritis has been increased since 1980's and many immunotherapeutic agents including disease-modifying antirheumatic drugs (DMARDs) were developed and became the mainstay of treatment of rheumatoid arthritis. However, the cure of the disease has hardly been achieved. In oriental medicine, rheumatoid arthritis is related to Bi-Zheng(痺證), that presents pain, swelling, andlor loss of joint function as major clinical manifestations, and also known to be deeply involved in suppression of immune function related to weakness of Jung-Ki(正氣). The herbal medicine, empirically used, could be a potential resource of development of new immunotherapeutic agents for rheumatoid arthritis. Methods : We developed a search strategy using terms to include "rheumatoid arthritis and herbal medicine" combined with "Chinese medicine" and/or "Oriental medicine". The search was focused on experimental studies of herbal medicine (January 1999 to May 2004), which is known to have effects on immune function of patients with rheumatoid arthritis. Computerized search used Internet databases including KISS and RISS4U (Korea), CNKI (China), MOMJ (Main Oriental Medicine Journal, Japan), and PubMed. The articles were selected from journals of universities or major research institutes. Results : The literature search for experimental studies on effects of herbal medicine on immunity of rheumatoid arthritis retrieved a total of 21 articles (Korea; 8, China ; 12, Japan ; 1). Of 21 articles, 10 were related to single-drug formula, 2 to drug interaction, and 9 to multi-drug formula. Single-drug formula was mainly used for aqua-acupuncture and researches on active components. Studies of drug interaction emphasized harmony of Ki-Hyul(氣血) and balance of Han-Yeul(寒熱). Multi-drug regimen was mainly found among formulas for Bo-Ki-Hyul(補氣血) and Bo-Sin(補腎). Conclusion : Studies on rheumatoid arthritis were performed both in vitro and in vivo in vitro study, LPS-stimulated splenocytes and synoviocytes were treated with herbal medicine, resulting in proliferation and activation of immune cells and suppression of cytokine activities in vivo study CIA animal model demonstrated that herbal medicine decreased antibody production and improved function of immune cells. In cellular and molecular study herbal medicine showed profound effects on the level of mRNA expression of certain cytokines related to immune function. This study revealed that herbal medicine has significant immune modulatory action and could be used for recovery of immune dysfunction of rheumatoid arthritis patients.

사상체질에 따른 류마티스 관절염의 위해요인 및 TNF-α(G308A) 유전자 다형성간의 연관성 연구

김수영,전형준,이두익,이윤호,최도영,유용구,이재동 대한침구의학회 2007 대한침구의학회지 Vol.24 No.1

Objectives : The purpose of this study is to examine the risk factors and the genetic polymorphism of TNF-alpha associated with rheumatoid arthritis by Sasang constitution Methods : This study was planned to detect the susceptibility of the patients diagnosed by rheumatoid arthritis to Sasang Constitution and to examine the risk factor such as life style and environmental stress (smoking, environmental tobacco smoke, alcohol intake and so on). The genetic polymorphism of TNF-alpha (G308A) were analyzed by PCR-RFLP in rheumatoid arthritis patients and controls. Rheumatoid arthritis patients and matched controls are assessed with QSCCⅡ question for Sasang Typology. Then the genetic polymorphism of patients by Sasang constitution are compared to those of control, which are statistically analyzed and adjusted by age, sex, smoking status, alcohol intake, BMI, and econocmic status. Results : Differential effect of passive smoking on the association between Sasang constitution and rheumatoid arthritis risk was found. This study showed that the genetic polymorphism (TNF-α(G308A)) of rheumatoid arthritis patients and controls associated with the susceptibility to rheumatoid arthritis by sasang constitution was analyzed. Differential effects of TNF-α(G308) genetic polymorphism on the association between rheumatoid arthritis risk and Sasang constitution were found. Conclusion : It is suggested that the genetic polymorphism correlated with susceptibility to rheumatoid arthritis by specific sasang constitution used as its susceptibility marker and further as basic data to prevent the risk factors for rheumatoid arthritis. But larger studies will be needed to confirm these preliminary findings.

海桐皮藥鍼이 Collagen-induced Arthritis 억제 및 면역조절에 미치는 영향

김영화,이현 대한침구의학회 2007 대한침구의학회지 Vol.24 No.5

Objectives : The purpose of this study was to analyze the effects of Erythrinae Cortex herbal- acupuncture solution(EC-HAS) at the Joksamni(ST36) of mice with collagen II-induced arthritis(CIA). Methods : The author performed several experimental procedures to observe the effects of the EC-HAS at the arthritis. The severity of arthritis, changes of cytokine level and antibody level, histological changes of the CIA mouse joint were analyzed. Results : 1. The incidence of arthritis and arthritis index were significantly decreased in the cases which were treated with the EC-HA. 2. Cartilage destruction and synovial cell proliferation were reduced, and the expression of the collagen fibers was similar with that of the normal group. 3. The levels of IL-6, IFN-γ, TNF-α, IL-1β in serum of the CIA mice which were treated with the EC-HA were significantly decreased compared with those of the normal group. 4. The levels of IgG, IgM and anti-collagen Ⅱ in serum of CIA mice when they treated with the EC-HA were significantly decreased compared with those of the normal group. 5. The expression ratio of CD4+ to CD8+ cells in the EC-HA treated mice were maintained as much as the normal group of the lymph nodes in the CIA mice. 6. The CD3e+CD69+ and CD11b+Gr-1+ cell populations in the knee joint were significantly decreased in the EC-HA treated group. Conclusions : These results suggest that the EC-HA at the ST36 may be responsible roles to control on the synovial cell proliferation and to prevent the cartilage destruction in rheumatoid arthritis. These results will be important supporting evidence for the practical use of the EC-HA at rheumatoid arthritis clinic in the future. Objectives : The purpose of this study was to analyze the effects of Erythrinae Cortex herbal- acupuncture solution(EC-HAS) at the Joksamni(ST36) of mice with collagen II-induced arthritis(CIA). Methods : The author performed several experimental procedures to observe the effects of the EC-HAS at the arthritis. The severity of arthritis, changes of cytokine level and antibody level, histological changes of the CIA mouse joint were analyzed. Results : 1. The incidence of arthritis and arthritis index were significantly decreased in the cases which were treated with the EC-HA. 2. Cartilage destruction and synovial cell proliferation were reduced, and the expression of the collagen fibers was similar with that of the normal group. 3. The levels of IL-6, IFN-γ, TNF-α, IL-1β in serum of the CIA mice which were treated with the EC-HA were significantly decreased compared with those of the normal group. 4. The levels of IgG, IgM and anti-collagen Ⅱ in serum of CIA mice when they treated with the EC-HA were significantly decreased compared with those of the normal group. 5. The expression ratio of CD4+ to CD8+ cells in the EC-HA treated mice were maintained as much as the normal group of the lymph nodes in the CIA mice. 6. The CD3e+CD69+ and CD11b+Gr-1+ cell populations in the knee joint were significantly decreased in the EC-HA treated group. Conclusions : These results suggest that the EC-HA at the ST36 may be responsible roles to control on the synovial cell proliferation and to prevent the cartilage destruction in rheumatoid arthritis. These results will be important supporting evidence for the practical use of the EC-HA at rheumatoid arthritis clinic in the future.

류마티스 관절염의 질병활성도 지표로써 모발의 미세원소 농도

전재범 ( Jae Bum Jun ),김태환 ( Tae Hwan Kim ),김승영 ( Seung Young Kim ),김평남 ( Pyoung Nam Kim ),정성수 ( Sung Soo Jung ),이인흥 ( In Hong Lee ),배상철 ( Sang Cheol Bae ),유대현 ( Dae Hyun Yoo ),주경빈 ( Kyung Bin Joo ),김성윤 대한류마티스학회 1995 대한류마티스학회지 Vol.2 No.1

연구 배경: 아연과 구리는 인체에서 두번째와 세번째로 많이 존재하는 미세원소로, 면역기능에 관계하는 것으로 알려져 있다. 류마티스 관절염은 대표적인 자가면역성 질환으로 혈청 아연은 감소하고 혈청 구리는 증가한다고 한다. 최근 미세원소를 모발에서 측정하는 연구가 많은데, 이는 모발이 갖는 여러가지 장점때문이다. 그러나 류마티스 관절염 환자의 모발에서 미세원소를 측정한 연구는 없다. 저자들은 류마티스 관절염 환자의 모발에서 미세원소를 측정하고 질병 활성도와의 연관성을 알아보고자 한다. 방법: 류마티스 관절염 환자 50명과 퇴행성 관절염 환자 22명을 대상으로 유도결합플라즈마 원자방출분광법으로 모발의 아연과 구리농도를 측정하였다. 결과: 1) 구리의 농도는 류마티스 관절염 환자에서 15.42±6.29 ppm이었고, 퇴행성 관절염 환자에서는 15.41±7.49 ppm (p>0.05)으로 유의한 차이를 보이지 않았다. 아연의 농도도 각각 197.59±80.18ppm, 201.14±60.68 ppm(p<0.05)으로 유의한 차이를 보이지 않았다. 2) 질병활성도를 나타내는 여러가지 지표들과 류마티스 관절염 환자 모발의 미세원소 농도는 유의한 연관성을 보이지 않았다. 결론: 류마티스 관절염 환자 모발의 미세원소는 퇴행성 관절염 환자의 미세원소 농도와 유의한 차이가 없었으며, 질병활성도를 나타내는 지표와 의미있는 연관성을 보이지 않아 질병활성도의 지표로는 유용하지 않을 것으로 사료된다. Objective: Zinc and copper are the second and third most abundant trace elements following iron in the human body. Zinc and copper have important effects on humoral and cell-mediated immunity. In patients with rheumatoid arthritis, it has been reported that serum zinc level is decreased and seurm copper level increased. But no reports are available for the trace element level of hair in patients with rheumatoid arthritis. We studied to investigate the significance of trace element level of hair in rheumatoid arthritis patients, particularly its relation to disease activity. Methods: The trace element level of hair was estimated in 50 patients with rheumatoid arthritis and 22 osteoarthritis patients by inductively coupled plasma atomic emission spectrometry and was investigate the correlation to various disease activity indices of rheumatoid arthritis. Results: The results were as follows: 1) There was no significant difference in either the zinc or copper level in hair between patients with rheumatoid arthritis and osteoarthritis. 2) No correlation was observed between the zinc or copper level in hair and age or disease duration for rheumatoid arthritis patients. 3) Zinc and copper levels of hair did not correlate with various indices of disease activity in rheumatoid arthritis patients. Conclusions: Zinc and copper levels of hair in rheumatoid arthritis patients were not different from those of osteoarthritis and did not correlate with disease activity indices. Studies on the effect of antirheumatic drug therapy on trace element level of hair are necessary.

류마티스 관절염에 있어 종양괴사인자 다형성에 대한 연구

김경운,한미영,이윤경,이경민,이봉효,임성철,정태영,서정철 대한침구의학회 2007 대한침구의학회지 Vol.24 No.3

Objectives : Tumor necrosis factor-α(TNF-α) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis. This study was designed to investigate the relation between TNF-α gene polymorphism and rheumatoid arthritis in Korean population. Methods : This study was carried out on 103 rheumatoid arthritis patients who fulfilled the American College of Rheumatology 1987 revised criteria for rheumatoid arthritis and 208 healthy control subjects. Blood samples from all subjects were obtained for DNA extraction. The extracted DNA was amplified by polymerse chain reaction(PCR). PCR products were visualized by 2% agarose gel electrophoresis. We investigated the genotyping of TNF-α by using Pyrosequencing. Results : The genotypes of TNF-α gene were GG, AG and AA. While the distribution of TNF-α polymorphism in control subjects was 92.31%, 7.21%, 0.48% respectively, in rheumatoid arthritis patients was 93.20%, 6.80%, 0.00%(GG, AG, AA). There was no statistical significant allelic frequency difference between control and rheumatoid arthritis groups.Conclusions : We concluded that there was no significant association between TNF-α gene polymorphism and rheumatoid arthritis. However, the findings of this study need to be confirmed in more patients and further studies.

사상체질에 따른 류마티스 관절염 환자 대조군 연구

김수용,이상훈,이현종,이두익,이윤호,이재동 대한침구의학회 2004 대한침구의학회지 Vol.21 No.1

Objective: The purpose of this study is to examine the susceptibility of the patients diagnosed by rheumatoid arthritis to Sasang Typology. Methods: This study are planned to detect the susceptibility of the patients diagnosed by rheumatoid arthritis to Sasang Typology. In order to analyze the susceptibility of rheumatoid arthritis to Sasang Typology, 147 rheumatoid arthritis patients and 147 matched controls are assessed with QSCCⅡ question for Sasang Typology. Then the frequencies of patients by Sasang constitution are compared to those of control, which are statistically analyzed and adjusted by age, sex, smoking status, alchol intake, BMI, and economic status. Results: The demographic characteristics of the study population are similar in sex and age distribution, smoking status, and alcohol intake (p>0.05). 147 rheumatoid arthritis patients and 147 matched controls are assessed with QSCCⅡ question for Sasang constitution. Soeumin is the most susceptible to rheumatoid arthritis compared to Taeumin or Soyangin (Crude OR[95% CI]; 3.82[2.19-6.64]). It is statistically significant after adjusting age, sex, smoking status, alcohol intake, BMI, and economic status (Adjusted OR[95% CI]; 3.01[1.47-6.15]). Conclusions: It is suggested that the specific Sasang Typology associated with rheumatoid arthritis is used as its susceptibility marker and further as basic data to prevent the risk factors for rheumatoid arthritis.

건강보험 청구자료를 이용한 한국인 염증성 관절염 환자의 뇌졸중 발생 분석

Kijeong Lee,Jung-Kyu Choi,Jin-su Park,Jung Yoon Pyo,Minkyung Han,Jun Hong Lee 대한임상노인의학회 2022 대한임상노인의학회지 Vol.23 No.2

Background: Inflammation is an important mechanism in stroke. To a considerable extent, the pathophysiology of inflammatory arthritis is influenced by inflammatory cells and cytokines. We compared the risk of stroke between patients with inflammatory arthritis and matched controls, using data from the National Health Insurance Service. Methods: Using a combination of primary diagnosis and V codes for rare incurable diseases, we defined the patients with ankylosing spondylitis, seropositive rheumatoid arthritis, and psoriatic arthritis and enteropathic spondyloarthropathy. The control group was defined by 1:5 propensity score-matching for each disease. Newly developed stroke was identified in the patients with the primary diagnosis of (I60-64) and 1) brain imaging or 2) a prescription of stroke medication or related intervention. Results: The occurrence of stroke was more frequently associated with seropositive rheumatoid arthritis in both the patient population and the seropositive rheumatoid arthritis control group (hazard ratio 1:11, 95% CI 1.02-1.20, P=0.012). In this study, the frequency of stroke occurrence was not associated with the diagnosis of ankylosing spondylitis nor psoriatic arthritis or enteropathic spondyloarthropathy. Furthermore, the use of biologic agents was not associated with the occurrence of stroke, using multivariable analyses in the three different types of inflammatory arthritis and their respective control groups. Conclusion: Seropositive rheumatoid arthritis was a predictor of frequent stroke occurrences. The patients with seropositive rheumatoid arthritis must be cautious with regard to the occurrence of a comorbid stroke. Further studies with long-term follow-ups of clinical outcomes are warranted to explain the underlying correlation between inflammatory arthritis and the risk of stroke.

연골표면에 침착한 면역물질의 양상에 관한 연구

유대현(Dae Hyun Yoo),정성수(Sung Soo Jung),이인홍(In Hong Lee),배상철(Sang Cheol Bae),김성윤(Seong Yoon Kim),김신규(Think You Kim),정현기(Hyun Kee Chung),최일용(Il Yong Choi) 대한내과학회 1993 대한내과학회지 Vol.45 No.6

N/A Background: Immune deposits were found on the articular surface of rheumatoid arthritis and osteoarthritis even though the prevalence and pattern of immune deposits were differnt between rheumatoid arthritis and osteoarthritis. Authors conducted this study to compare the pattern and positive rate of immune deposits on surface of articular cartilage between rheumatoid arhtritis and osteorthritis. Methods: Articular cartilages were obtained from patients who were conducted total joint replacement surgery at knee or hip joint. Selected cases were 15cases of rheumatoid arthritis, 45cases of osteoarthritis. Immune deposits were searched using direct immunofluorescent technique with FITC conjugated anti-IgG, IgA, IgM, C, antibody. Results: 1) Positive rate of immune deposits on articular cartilage was 66.7% in rheumatoid arthrtis and 26.7% in osteoarthritis. 2) Granular staining pattern was found in only 6patients out of 10positive patients with rheumatoid arthritis. In osteoarthritis, the pattern of immune deposits was not granular but nongranular pattern such as intermittent linear or linear pattern. 3) Positive rate in primary osteoarthrits and secondary arthritis was 32%, and 26.7% respectively. 4) Rheumatoid factor was reactive not only in 6cases with granular pattern but also in 3cases without immune deposits and in 2cases with nongranular pattern. Coclusion: Immune deposits was found more frequently in rheumatoid arthritis than osteoarthritis and granular pattern was noted in cases with rheumatoid arthritis only. The differences in prevalence and pattern of immune deposits between rheumatoid arthritis and osteoarthritis may be due t different antigen, mechanism of immune deposition or another unknown factors. Further investigation have to be conducted in these respects.

류마티스 관절염 환자에서 leflunomide 복용 중 발생한 용혈성 빈혈 1예

박소연,백수영,박세우,김주형,손창남,조수경,김일,배상철 대한임상약리학회 2008 Translational and Clinical Pharmacology Vol.16 No.2

Leflunomide is a new isoxazole based disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis. Leflunomide alone or combination with methotrexate has been reported to be safe as well as effective in patients with rheumatoid arthritis. Although a few cases of leflunomide-induced pancytopenia were identified, leflunomide-induced hemolytic anemia in rheumatoid arthritis has not been reported yet. We present a case of leflunomide-induced hemolytic anemia in a patient with rheumatoid arthritis. Leflunomide is a new isoxazole based disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis. Leflunomide alone or combination with methotrexate has been reported to be safe as well as effective in patients with rheumatoid arthritis. Although a few cases of leflunomide-induced pancytopenia were identified, leflunomide-induced hemolytic anemia in rheumatoid arthritis has not been reported yet. We present a case of leflunomide-induced hemolytic anemia in a patient with rheumatoid arthritis.