Anti-Neutrophil Cytoplasmic Antibody의 임상적 의의와 검출에 대한 연구 : 형광현미경법과 유식세포분석법의 비교

서을주,김대원,박정식,김성권 대한임상병리학회 1992 대한임상병리학회지 Vol.12 No.3

Stratification of Nuclear Homogeneous Patterns on HEp-2 Cells Based on Neutrophil Nuclear Staining

원동일,박지혜,김범수,김채은,윤현식,정지수 전남대학교 의과학연구소 2021 전남의대학술지 Vol.57 No.1

Antinuclear antibody (ANA) testing is used to diagnose systemic autoimmune rheumatic disease (SARD). Nuclear homogeneous patterns on ANA-HEp-2 cells can result from anti-double-stranded DNA (dsDNA), anti-nucleosome, anti-histone, anti-Scl-70, or anti-dense fine speckles 70 (DFS70) antibodies (Abs). This study aimed to find a way to discriminate DFS70 Abs from others by way of assessing neutrophil nuclear staining on anti-neutrophil cytoplasmic antibody (ANCA) testing. Nuclear staining on ANCA- neutrophils was assessed to stratify nuclear homogeneous patterns on ANA-HEp-2 cells. Enrolled subjects included (1) young individuals with a dense fine speckled pattern on ANA testing (young non-SARD group, n=71) and patients with (2) systemic lupus erythematosus (SLE group, n=35); (3) rheumatoid arthritis possibly with histone, nucleosome Abs, and others (RA group, n=51); and (4) diffuse systemic sclerosis with Scl-70 Abs (diffuse SSc group, n=19). Negative rates (95% confidence interval) of neutrophil nuclear staining were 97.2% (90.2%-99.7%) in the young non-SARD group, 2.9% (0.1%-14.9%) in the SLE group, 3.9% (0.5%-13.5%) in the RA group, and 47.4% (24.5%- 71.1%) in the diffuse SSc group. The negative rate of the young non-SARD group was significantly higher than those of the other groups (all p<0.05). In conclusion, this study suggests that the assessment of nuclear staining on ANCA-neutrophils can help to stratify nuclear homogeneous patterns on ANA-HEp-2 cells and thus to determine whether the ANA pattern is attributed to DFS70 Abs, which can be found in healthy individuals, especially in young individuals.

증례 : 신장 ; p-ANCA가 동시에 검출된 항사구체 기저막 항체 질환 2예

강건우 ( Gun Woo Kang ),황은아 ( Eun Ah Hwang ),한승엽 ( Seung Yeup Han ),박성배 ( Sung Bae Park ),김현철 ( Hyun Chul Kim ),최미선 ( Mi Sun Choe ) 대한내과학회 2012 대한내과학회지 Vol.83 No.4

Anti-glomerular basement membrane antibody (anti-GBM Ab) disease is characterized by circulating antibodies to the glomerular basement membrane and the deposition of IgG or, rarely, IgA along the glomerular basement membrane. This disease accounts for 10-20% of crescentic glomerulonephritis. We report two patients with anti-GBM Ab disease who were positive for perinuclear-anti-neutrophil cytoplasmic antibody (p-ANCA). Percutaneous renal biopsies showed many crescent formations and linear deposits of IgG along the glomerular basement membrane. Serologic tests for p-ANCA were positive. They were treated with steroid pulse and cyclophosphamide and one patient also underwent plasma exchange therapy. Despite immunosuppressive therapy, their renal functions did not improve and both required regular hemodialysis. (Korean J Med 2012;83:514-519)

항호중구세포질항체 검사에서 혼합된 형광양상의 판독을 위한 디지털 화상분석기법의 개발

서정욱 ( Jung Uk Sir ),김신규 ( Think You Kim ) 대한류마티스학회 2004 대한류마티스학회지 Vol.11 No.4

Objective: Anti-neutrophil cytoplasmic antibody (ANCA) is an important marker for the diagnosis and the classification of rheumatic diseases and systemic vasculitis. If the autoantibodies that can be stained in the nucleus of neutrophil used for substrate of ANCA test, there`s a need for its differential diagnosis from real p-ANCA. This paper focuses on digital image processing technique for the differentiation of p-ANCA without performing additional tests. Methods: Positive ANCA results which showed mixed fluorescent pattern were transformed into digital image. Using Matlab (MathWorks, U.S.A.), we developed 2D to 3D transformation method and virtual tomography for the interpretation of mixed fluorescent pattern, and compared these results with ANA and anti-DNA test by indirect immunofluorescence (IIF) method using IT-AIT, IT-ANCA, and IT-DNA kit (ImmunoThink, Korea). Results: By applying the 3D transformation method and virtual tomography to the results of ANCA test where combined antibodies exist, we were able to separate each different fluorescent pattern that were difficult to separate by manual reading. Conclusion: The new digital image analysis methods developed in this study displace some of the disadvantages of IIF method. Therefore, these methods can easily be applied to complex samples, and can allow rapid and accurate tests for rheumatic diseases and other autoimmune diseases.

핵주변항호중구세포질항체와 연관된 경수막염에 동반된 양안 안와첨부증후군

최용제,최정윤,양희경 대한안과학회 2020 대한안과학회지 Vol.61 No.5

Purpose: To report a rare case of perinuclear anti-neutrophil cytoplasmic antibody-associated pachymeningitis presenting as bilateral orbital apex syndrome. Case summary: A 79-year-old female presented with a visual acuity decrease and ophthalmoplegia in both eyes from 1 week prior to her visit. Orbital magnetic resonance imaging showed diffuse hypertrophy and enhancement of the dura mater near the optic canal and superior orbital fissure causing orbital apex syndrome. The serum titer of perinuclear anti-neutrophil cytoplasmic antibody was elevated. Based on these findings, she was diagnosed with pachymeningitis related to perinuclear anti-neutrophil cytoplasmic antibody-associated vasculitis. The antibody titers decreased and ophthalmoplegia recovered after treatment with high dose intravenous steroid injection, cyclophosphamide, and long-term maintenance therapy with oral azathioprine and prednisolone. However, her visual acuity did not improve in either eye. Conclusions: Perinuclear anti-neutrophil cytoplasmic antibody associated vasculitis can present as orbital apex syndrome and should be considered as a differential diagnosis. 목적: 핵주변항호중구세포질항체와 연관된 혈관염에 동반된 경수막염에서 발생한 양안 안와첨부증후군 환자 1예를 보고하고자 한다. 증례요약: 79세 여자가 1주 전에 발생한 두통과 양안 시력저하 및 눈운동장애를 주된 소견으로 내원하였다. 안와 자기공명영상검사상 특징적인 경막의 비후가 확인되고 비후된 경막이 시신경관과 상안와열에서 시신경과 눈운동신경을 압박하는 안와첨부증후군 소견이 관찰되었다. 혈액검사 결과 핵주변항호중구세포질항체가 확인되어 핵주변항호중구세포질항체 연관 경수막염으로 진단하였다. 고용량스테로이드 정주 및 사이클로포스파마이드 병행 치료를 하였으며, 이후 경구 아자티오프린 및 프레드니솔론을 유지하였다. 치료 후 핵주변항호중구세포질항체 역가가 음전되었고 눈운동장애는 모두 호전되었으나 시력은 전혀 호전되지 않았다. 결론: 핵주변항호중구세포질항체 연관 혈관염과 관련된 경수막염 환자에서 안와첨부증후군이 초기 증상으로 나타날 수 있으므로 감별하는 것이 중요하다.

항호중구 세포질 항체(ANCA) 양성으로 진단된 Wegener 육아종증 3예

허정숙,이수형,박성배,김현철,박관규,이상숙 대한내과학회 1993 대한내과학회지 Vol.44 No.2

Wegener씨 육아종은 상ㆍ하기도의 괴사성육아종, 사구체신염, 전신의 작은 혈관을 침범하는 복합임상증후군으로서 최근 이 질환에서 항호중구세포질항체(anti neutrophil cytoplasmic antibody)가 특이하게 나타나고 있어 이 질환의 진단과 치료에 대한 반응의 지표로서 널리 이용되고 있다. 저자들은 최근 임상적으로 Goodpasture 증후군과 흡사한 중독한 폐출혈과 괴사성 사구체신염을 나타낸 환자에서 ANCA 양성을 나타낸 Wegener씨 육아종 3예를 경험하였다. 3예 모두 여자환자였으며 임상증상으로 3예 모두에서 혈뇨, 객혈, 발열, 전시쇠약감이 있었으며 3예중 2예에서 관절통이 관찰되었다. 침범된 장기별로는 신장, 폐, 눈, 구강은 3예 모두 침범되었으며 피부 및 관절이 각각 1예에서 침범되었고 중이, 심장, 신경계 침범은 한 예도 없었다. 검사실소견에서 3예 모두에서 중등도이상의 빈혈, ESR 증가, 단백뇨, 혈뇨, 혈청글로 불린상승이 있었고 3예중 2예에서 신부전증이 있었다. 혈청학적 이상소견은 3예 모두에서 Rheumatoid factor와 ANCA가 양성이었고 3예 모두 항 사구체 기저막 항체 및 항핵항체(ANA)가 음성이었고 혈청보체치도 모두 정상이었다. 흉부 X-선 소견으로는 3예 모두에서 양폐에 다발성의 반점상 및 결절성 침윤이 심하였으며 공동 및 늑말삼출은 각각 1예에서 관찰되었다. 치료로는 3예중 2예에서는 혈액투석치료를 필요로 하였으며 이중 1예는 인공호흡기 치료를 필요로하는 중증환자였다. 3예중 2예에서 스테로이드 충격요법을 받았으며 이 가운데 1예에서 극적반응이 있었으나 다른 1예는 치료에 대한 반응이 없었다. 입원당시 이미 심한 신부전이 있었던 2예는 각종 치료에도 불구하고 사망하였고 입원당시 신기능이 정상이었던 1예는 스테로이드 충격요법으로 폐침범이 극적 호전되어 생존하였고 그후 cyclophosphamide 치료로 신기능도 정상으로 회복되었다. WG is a syndrome characterized by necrotizing granulomatous lesions in the upper and lower respiratory tracts, glomerulonephritis, and a generalized vasculitis involving both arteries and veins. Recently ANCA has been reported to be a highly specific test for the diagnosis of WG. We have experienced three patients with ANCA positive WG whose initial clinical presentation mimicked Goodpasture's syndrome. All three patients were female with mean age of 30 years(16-53). The major presenting signs and symptoms were hemoptysis, fever, general weakness, gastrointestinal symptoms, and conjunctivitis. Persistent rhinorrhea was seen in only one patient. All patients had lung, renal, and eye involvement, but none of the patients had signs of ear, heart or nervous system involvement. All three patients had moderate anemia,elevated ESR and urinary abnormality. One patient had leukopenia, and no patient had thrombocytopenia. All three patients were positive for rheumatoid factor and ANCA. None were positive for antinulear antibody, anti-GBM antibody, or cryoglobulin. Serum complement levels were normal in all three cases. Radiographic studies of chest showed multiple bilateral patches and nodular infilterates in all three patients. Cavitation was seen in one case and pleural effusion in one case. Two patients were treated with steroid pulse therapy, one of them showed dramatic improvement, the other patient expired due to progression of underlying illness. One patient whose renal function was normal at the time of admission recovered, but the other two patients who required hemodialysis treatment expired. In conclusion, earlier diagnosis of WG facilitated by ANCA tests may help reduce the higher morbidity and mortality seen in this type of patient.

Long-term Prognosis of Anti-Neutrophil Cytoplasmic Antibody- Negative Renal Vasculitis: Cohort Study in Korea

이성우,유미연,백선하,안신영,김세중,나기영,채동완,진호준 대한의학회 2016 Journal of Korean medical science Vol.31 No.4

Few studies have reported on the long-term prognosis of anti-neutrophil cytoplasmic antibody (ANCA)-negative renal vasculitis. Between April 2003 and December 2013, 48 patients were diagnosed with renal vasculitis. Their ANCA status was tested using indirect immunofluorescence and enzyme-linked immunosorbent assays. During a median (interquartile range) follow-up duration of 933.5 (257.5-2,079.0) days, 41.7% of patients progressed to end stage renal disease (ESRD) and 43.8% died from any cause. Of 48 patients, 6 and 42 were ANCA-negative and positive, respectively. The rate of ESRD within 3 months was higher in ANCA-negative patients than in ANCA-positive patients (P = 0.038). In Kaplan-Meier survival analysis, ANCA-negative patients showed shorter renal survival than did ANCA-positive patients (log-rank P = 0.033). In univariate Coxproportional hazard regression analysis, ANCA-negative patients showed increased risk of ESRD, with a hazard ratio 3.190 (95% confidence interval, 1.028-9.895, P = 0.045). However, the effect of ANCA status on renal survival was not statistically significant in multivariate analysis. Finally, ANCA status did not significantly affect patient survival. In conclusion, long-term patient and renal survival of ANCA-negative renal vasculitis patients did not differ from those of ANCA-positive renal vasculitis patients. Therefore, different treatment strategy depending on ANCA status might be unnecessary.

Anti-neutrophil cytoplasmic antibody-associated vasculitis secondary to human immunodeficiency virus infection: a case report

( Kyung Bae Chung ),( Doyoung Kim ) 대한피부과학회 2021 대한피부과학회 학술발표대회집 Vol.72 No.2

만성 염증성 장질환 환자에서 항호중구 세포질 항체의 의의

문윤재(Yoon Jae Moon),배희동(Hee Dong Bae),박효진(Hyo Jin Park),김원호(Won Ho Kim),정석훈(Suk Hoon Chung),김현숙(Hyun Sook Kim),전재윤(Chae Yoon Chon),박인서(In Suh Park) 대한내과학회 1997 대한내과학회지 Vol.52 No.5

N/A Objective: Anti-neutrophil cytoplasmic antibody (ANCA), known as a useful diagnostic marker in patients with ulcerative colitis (UC), are specific for granule proteins of granulocytes and monocytes and induce distinct fluorescence patterns. To evaluate the significance of ANCA in chronic inflammatory bowel disease (IHD), the presence of ANCA in chronic IBD was studied using indirect immunofluorescent test (IIF), Methods: Between March, 1994 and September 1995, 51 patients with chronic inflammatory bowel disease were subjected in this study. We had analysed the correlation between duration, disease activity, location by colonoscopy and radiologic examinations, steroid treatment. Results: 1) Among 34 patients with ulcerative colitis (UC), ANCA was demonstrated in 23 patients (67.6%). Among 19 patients with other chronic IBD (4 Crohn's disease, 6 Behcet's colitis, 7 intestinal tuberculosis and 2 radiation colitis) 2 patients (10.5%) had ANCA. The positivity of ANCA in patients with UC was significantly higher than in patients with other chronic IBD. 2) In patients with UC, c-ANCA was positive in 2 (5.9%) patients and p-ANCA was positive in 21 (61.8%) patients. In patients with other chronic IBD, ANCA was positive in one patient with Behcet's colitis or one patient with intestinal tuberculosis but negative in all patients with Crohn's disease or radiation colitis. 3) The mean duration of disease in ANCA positive patients was 42.4±39.4 months and the mean duration of disease in ANCA negative patients was 44.9±36.8 months, but there was no significant difference. 4) The number of patients in clinically mild, moderate and severe group were 23 (37.6%), 6 (83.2%) and 5 (14.7%) respectively. Among these groups the number of ANCA positive patients were 15 (65.2%), 5 (83.2%) and 3 (60%) respectively, but there was no significant difference. 5) The number of patients with proctitis, left side colitis and pancolitis were 9 (26.5%), 14 (41.2%) and 11 (32.4%) respectively, Among these groups the number of ANCA positive patients were 4 (44.4%), 10 (71.4%) and 9 (81.8%) respectively, but there was no significant difference. 6) Among 13 patients with steroid treatment 9 patients (69.2%) were ANCA positive. Among 21 patients without steroid treatment 16 patients (76.2%) were ANCA positive, but there was no significant difference. Conclusion: Although there was no correlation between ANCA and duration, disease activity, location or steroid treatment in UC patients, ANCA could be a diagnostic marker of UC in chronic IBD patients.

Lipid Profiles in Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis: A Cross-sectional Analysis

( Sung Soo Ahn ),( Taejun Yoon ),( Jason Jungsik Song ),( Yong-beom Park ),( Sang-won Lee ) 대한류마티스학회 2020 대한류마티스학회지 Vol.27 No.4

Objective. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease (AID) characterised by necrotising intravascular inflammation. Growing evidence suggests that immune system triggers altered lipid metabolism in AIDs. We investigated whether changes in lipid profile correlate with severity of disease in AAV. Methods. Seven lipid profiles were evaluated utilizing frozen serum samples from 67 patients registered in the Severance Hospital ANCA-associated VasculitidEs cohort by a chemistry autoanalyzer. The Birmingham Vasculitis Activity Score (BVAS) version 3 was used to measure patient’s assessment of global disease activity. The relationship between the BVAS with continuous variables was calculated by Pearson’s correlation analysis. Results. Thirty-five (52.2%), 19 (28.4%), and 13 (19.4%) patients were diagnosed with microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis, respectively. Patients’ mean age was 60.0 years, and 22 (32.8%) were male. Among the lipid profiles investigated, total cholesterol, high-density lipoprotein, and low-density lipoprotein, and apolipoprotein A1 and B were significantly associated with BVAS; apolipoprotein A1 showed the highest correlation with BVAS (r=-0.521, p<0.001), remaining consistent even in patients with new-onset disease (r=-0.430, p=0.012). Apolipoprotein A1 had the highest association with the renal manifestation score among the clinical scores comprising BVAS (r=-0.457, p<0.001). Conclusion. Decreased lipid levels, especially apolipoprotein A1, are relevant to increased AAV disease activity, and differ according to organ involvement. Measuring lipid profiles could have clinical implications regarding the assessment of global disease activity and organ involvement patterns. (J Rheum Dis 2020;27:261 -269)