Crithidia luciliae 배양을 이용한 Anti - nDNA 검사에 관한 연구 1

김신규(Thin Kyou Kim),김성윤(Seong Yoon Kim) 대한내과학회 1988 대한내과학회지 Vol.35 No.4

N/A The detection of circulating anti-nDNA antibodies has played an importsnt role in the diagnosis and management of systemic lupus erythematosus. A number of methods are available but Crithidia luciliae indirect immunofluorescence (CLIF) assay has been confirmed as the simple and convenient method with high specificity. The suhstrates of CLIF have been imported with high expense. So we cultured C. luciliae in TTY-6 medium with modification, CLIF assay has done with ANA human reference serum (#l) supplied by AF-CDC. The result of the assay is 1:160 and this titer is located in the suggested range.

Hep - 2 세포배양을 이용한 항핵항체 ( ANA ) 검사에 관한 연구 1

김신규(Thin Kyou Kim),김성윤(Seong Yoon Kim) 대한내과학회 1988 대한내과학회지 Vol.35 No.3

N/A ANA test is most widely used screening test in the estigation of systemic rheumatic disease. The relility of the test is dependent on the choice of subrte. It is generally accepted that the cultured cell, espelly HEp-2 cell, ia better than the cryostat section of ue. o we cultured HEp-2 cells in DMEM with modifiea-ANA test has been done with ANA human reference am (#1, #2, #3, #6) supplied by AF-CDC. the fluorescence patterns and titers are placed in the gested patterns and ranges.

항경련제 복용 환자에서 항핵항체 양상

박필환 ( Pil Whan Park ),김신규 ( Thin Kyou Kim ) 대한류마티스학회 2002 대한류마티스학회지 Vol.9 No.4

Objective: This study set out to determine the antinuclear antibody (ANA) frequency and fluorescence pattern, as well as the incidence of drug-induced lupus (DIL) in patients on long term medications with anticonvulsants. Methods: Sera from 200 patients on medications with anticonvulsants for at least 6 months and from 105 healthy controls were tested by indirect immunofluorescence on immunotype (IT)-1 cells, and the medical records were retrospectively reviewed. The patients included 72 on valproic acid, 24 on phenytoin, 75 on carbamazepine, and 29 patients on two or more anticonvulsants. Results: ANA were positive in 3 of the 105 normal controls (3%). Twenty nine percent of patients on valproic acid, 26% on phenytoin, 8% on carbamazepine, and 34% on two or more different anticonvulsants were positive for ANA. The cytoskeletal pattern was prominent in patients on valproic acid and the speckled pattern in phenytoin. Most were of low titers. Conclusion: Long-term ingestion of valproic acid and phenytoin were shown to influence ANA, while carbamazepine was not. No definite relationship was observed between ANA positivity and DIL. However, positive ANA indicates effects of anticonvulsants on the immune system, and therefore progression to DIL cannot be ruled out. Therefore, patients on long-term medications with anticonvulsants should be regularly tested for ANA.

류마티스 관절염에서 질병활성 표지자로서의 중합 C9 검사의 유용성

서정욱 ( Jung UK Sir ),김신규 ( Thin Kyou Kim ) 대한류마티스학회 2005 대한류마티스학회지 Vol.12 No.3

목적: 류마티스 관절염은 만성적으로 진행되는 전신적인 염증성 질환이며 주요 관절의 변형이나 장애를 초래하게 된다. 질병활성 표지자(disease activity parameter)는 이러한 염증성 질환의 활성도를 측정하는 객관적인 지표로서 환자의 상태를 평가하고 치료계획을 수립하는데 중요한 역할을 하게 된다. 저자들은 류마티스 관절염에 대해 현재까지 알려져 있는 C반응성단백(C-reactive protein, CRP), 류마티스 인자(rheumatoid factor, RF), 적혈구침강속도(erythrocyte sedimentation rate, ESR) 등과 같은 질병활성 지표들의 결과와 최근에 소개된 시험관에서 보체를 활성화시킨 후 단일 클론성 항체를 사용하여 보체 활성의 최종 생성물인 중합 C9 (polymerized C9)을 정량적으로 측정하는 중합 C9 검사의 결과를 비교하여 류마티스 관절염의 새로운 질병활성 표지자로서의 유용성과 류마티스 관절염 환자에서 동반되는 신장병증의 예측인자로서의 가능성을 알아보고자 하였다. 방법: 미국 류마티스 협회의 류마티스 관절염 진단 기준에 의해 류마티스 관절염으로 진단 받은 대상 환자군(n=86)의 임상 소견 및 검사 소견을 종합하여 류마티스 관절염 활성군(active RA, n=43), 류마티스 관절염 비활성군(inactive RA, n=35) 및 신장병증을 동반한 류마티스 관절염군(RA with nephropathy, n=8)으로 분류하였고, 각 군에서 CRP, RF, ESR 및 중합 C9 검사(CAE, INCSTAR-DiaSorin, Italy)를 시행하였다. 각 검사간의 민감도와 특이도 비교는 ROC 곡선(receiver operating characteristic curve)을 통하여 시행하였고 통계처리는 ANOVA test를 시행하였다. 결과: CRP, RF, ESR 및 중합 C9 검사는 류마티스 관절염의 활성군과 비활성군의 비교에서 모두 통계적으로 유의한 차이를 보였고(p<0.05), ROC 곡선을 통한 각 검사간의 민감도와 특이도의 비교에서는 중합 C9 검사와 CRP 검사가 가장 우수한 결과를 보였다. 한편, 류마티스 관절염의 비활성군과 신장병증을 동반한 류마티스 관절염군의 비교에서는 중합 C9 검사만이 통계적으로 유의한 차이를 보였다(p<0.05). 결론: 중합 C9 검사는 류마티스 관절염에 있어서 질병 활성도를 잘 반영하는 새로운 질병 감시지표가 될 것으로 사료되며, 예후에 중요한 영향을 미치는 신장병증의 동반 유무를 예측할 수 있는 유용한 검사가 될 것으로 사료된다.

강직성 척추염과 미분화 척추염의 감별진단을 위한 HLA-Bw4 및 HLA-Bw6에 적용

오지하 ( Ji Ha Oh ),김신규 ( Thin Kyou Kim ),김태환 ( Tae Hwan Kim ) 대한류마티스학회 2002 대한류마티스학회지 Vol.9 No.3

목적: 척추 관절염과 HLA-B27의 연관성에 대해서는 잘 알려져 있고, 이 항원을 검사하는 표준방법인 세포독성검사법에는 B27 뿐만 아니라, HLA-B7과 공통 항원(broad specificity)인 HLA-Bw4와 HLA-Bw6가 포함되어 있다. HLA-B7은 B27과의 교차반응을 감별하기 위해서 그리고 공통 항원은 검사의 결과를 확인하기 위한 부수적인 목적으로 이용되어왔을 뿐, 이들 항원(HLA-B7, HLA-Bw4, HLA-Bw6)과 질환과의 연관성에 대한 연구는 HLA-B7을 제외하고는 없었다. 이 연구에서는 공통 항원인 HLA-Bw4와 HLA-Bw6를 이용하여 척추관절염의 진단에 이용하고자 하였다. 방법: 이 연구에서는 강직성 척추염 환자 259명과 미분화 척추염 환자 80명을 대상으로 HLA-B27 결과와 공통 항원에 따라 분류하였다. HLA-B27 검사는 세포독성검사법으로 시행하였다. 결과: 강직성 척추염이나 미분화 척추관절염을 가진 HLA-B27 양성 환자들을 공통 항원에 따라 구분한 결과, HLA-Bw4와 Bw6가 모두 양성인 강직성 척추염 환자가 151명(60.2%)이었고 HLA-Bw4만 양성인 경우는 100명(39.8%)이었다. 미분화 척추염 환자의 경우는 각기 27명(45.8%)과 32명(54.2%)으로 Bw4와 Bw6가 모두 양성인 경우가 Bw4만 양성인 경우에 비해 강직성 척추염의 빈도가 유의하게 높았다 (p값 0.044). 결론: HLA-B27 양성인 환자에서 종래에 부수적인 목적으로 이용되어왔던 HLA-Bw4와 HLA-Bw6의 결과는 강직성척추염을 미분화 척추염과 감별 진단하는 데 도움이 되었다.

전신성 류마티스 질환에서 항 ENA 항체에 관한 연구

배상철(Sang Cheol Bae),송관규(Gwan Gyu Song),이인홍(In Hong Lee),유대현(Dae Hyun Yoo),김성윤(Seong Yoon Kim),김신규(Thin Kyou Kim) 대한내과학회 1993 대한내과학회지 Vol.45 No.4

N/A Objectives: Among a variety of nuclear antigens, extractable nuclear antigens(ENA) which can be extracted from nuclei by homogenization in neutral saline contain ribonucleoprotin, Sm, SS-A/Ro, SS-B/La and other antigens. Characterization of anti-ENA anti-bodies provides information about nosology, subset definition within diseases, clinical activity, specific organ involvement and prognosis. Methods: Authors have used double immunodiffusion test to detect antibodies to ENAs and studied the frequencies of autoantibodies to these antigens and their correlation with clinical and laboratory features in systemic rheumatic diseases. Results: 1) 1,063 patients were investigated for the presence of serum antibodies to ENAs and 180 out of 1,063 patients (16.9%) had anti-ENA antibodies. 3,412 tests were performed for the presence of antibodies to Sm, RNP, Ro, La, Scl-70 and Jo-1 respectively and 230 out of 3,412 tests (6.7%) were positive. 2) The profiles of 137 patients who had anti-ENA antibodies are systemic lupus erythematosus (61), rheumatoid arthritis with secondary Sj6gren's syndrome (26) and without secondary Sjogren's syndrom (9), mixed connective tissue disease (18), scleroderma (10), polymyosits/dermatomyositis (6), undifferentiated connective tissue diease (4), gout (1), fibromyalgia syndrome (1) and Hashimoto's thyroiditis (1). 3) The frequencies of antibodes to ENAs were 73.5% in patiets with systemic lupus erythemtosus, 9.6% in rheumatoid arthritis, 100% in mixed connective tissue disease, 71.4% in scleroderma and 46.2% in polymyostis/dermatomyositis. 4) The frequencies of antibodies to Sm, RNP, Ro and La in patients with systemic lupus erythematosus were 18.1%, 41.5% 43.9% and 4.9% respectively. (1) Patients with anti-Sm antbodies had a higher incidence of pleuritis than those without anti-Sm antibodies(p=0.029). (2) Patients with anti-RNP anibodies had a higher incidence of Raynaud's phenomenon and pleuritis and a lower incidence of renal disease than those without anti-RNP antibodies (p=0.008, p=0.019, p=0.029). (3) Patients with anti-Ro antibodies had a higher incidence of thrombocytopenia than those without anti- Ro antibodies. (4) There were no clinical and laboratory differences between patients with anti-La antibodies and without anti-La antibodies. 5) In patients with rheumatoid arthritis, anti-Ro anti-body was likely to be associated wih secondary Sjogren syndrome, although statistically significant association was not found (p=0.063). Conclusions: These results showed that the detection of antibodies to ENAs by double immunodiffusion test was expected to be a useful diagnostic marker and predict some clinical features in systemic rheumatic diseases.

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.

복합 교원성 질환(Mixed connective tissue disease) 18예의 임상적 고찰

이인흥 ( In Hong Lee ),송관규 ( Gwan Gyu Song ),정성수 ( Sung Soo Jung ),배상철 ( Sang Cheol Bae ),유대현 ( Dae Hyun Yoo ),김신규 ( Thin Kyou Kim ),김성윤 ( Seong Yoon Kim ) 대한류마티스학회 1994 대한류마티스학회지 Vol.1 No.1

목적: 복합 교원성 질환은 1972년 Sharp 등에 의해서 처음 명명되었으며 전신성 홍반성 낭창, 다발성근염, 경피증의 임상적 양상을 함께 나타내는 질환으로서 고농도의 항 nRNP항체만이 양성 소견을 보이는 특징을 갖는다. 방법: 1989년 10월부터 1992년 9월까지 한양대학병원 류마티스 센터에서 MCTD로 진단된 18명의 환자를 대상으로 임상적 분석을 시행하였다. 결과: 1) Sharp의 진단기준에 부합되는 MCTD환자는 18명이었으며 모두 여자 환자였고 연령 분포는 23세에서 61세로 평균 38.6세였다. 2) 18명 모두가 관절통을 호소하였으며 이중에서 13명(72%)은 관절염 소견을 나타냈고, 류마티스인자는 15명(83%)에서 양성이었다. 3) 수부 부종(hand swelling)은 15명(83%)에서 관찰되었으며 18명 모두가 Raynaud 현상을 나타냈다. 4) 18명 모두가 근육통 소견을 보였으며, 12명에서 근육 조직검사 소견상 근염이 관찰되었다. 5) 혈청학 검사에서 항 핵항체와 항 nRNP항체는 18명 모두가 높은 역가를 나타냈으며 항 Sm항체는 모두 음성이었다. 결론: 향후 이 질환에 대한 보다 세밀한 임상 분석이 시행되기를 고대하며 이 질환에 대한 보다 많은 관심이 주어지기를 기대한다. Objective: Mixed connective tissue disease (MCTD) was first described by Sharp and coworkers in 1972 as distinct rheumatic diseases characterized by the overlapping features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and dermatomyositis/polymyositis and associated with the serologic marker anti-nRNP antibody at high titer. Methods: We reviewed 18 cases (all females) of MCTD who were admitted or visited to rheumatism center of Hanyang University Hopital, from October 1989 to September 1992. Results: 1) The average age at onset of MCTD was 38.6 years. The average duration of the disease was 5.3 years. 2) Raynaud`s phenomenon was found in 100%. Arthritis was found in 13 cases but rheumatoid factor was found in 15 cases. 3) Hand swelling was found in 15 cases and myositis was found in 56% (10 cases). 4) All patients with MCTD have anti-nRNP antibodies by high titer. In general, the titer does not correlate with disease activity. Conclusions: These data suggested that the clinical features of MCTD in Korean patients revealed similar to those of previous reports regarding foreign ethnic groups.

효소결합면역흡착법과 라텍스응집법을 이용한 요중 미량알부민의 측정

민도식,박일규,채정돈,이웅수,김신규,박필환 대한임상병리학회 2000 대한임상병리학회지 Vol.20 No.3