以肺部表现首发的抗中性粒细胞胞浆抗体相关性小血管炎临床分析

目的探讨以肺部表现首发的抗中性粒细胞胞浆抗体（ANCA）相关性小血管炎的临床特征。方法回顾分析10例以肺部症状首发的ANCA相关性小血管炎患者的临床资料。结果10例患者均有肺病变,肾脏损害5例,皮肤损害1例。所有患者ANCA阳性。双肺病变8例,单侧肺部病变2例。大部分患者可见血白细胞升高、贫血、血沉明显增快、C反应蛋白升高等。应用糖皮质激素及免疫抑制剂治疗,死亡3例,完全缓解7例。结论ANCA相关性小血管炎临床表现缺乏特异性,ANCA检查有助于该病的早期诊断。糖皮质激素及免疫抑制剂治疗能改善预后。     

抗中性粒细胞胞浆抗体与血管炎

讨论Ｈｉｌｂｅｒｔ空间上标型谱算子的基本性质。推广关于次正规算子不变子空间存在性的Ｂｒｏｗｎ定理以及关于本质正规算子本质本等价的Ｂｒｏｗｎ－Ｄｏｕｇｌａｓ－Ｆｉｌｌｍｏｒｅ定理。     

抗中性粒细胞胞浆抗体相关性血管炎的诊治进展

抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（ANCA-associated vasculitis,AAV）是一类病因不明的慢性自身免疫性系统性疾病,病理学特征为小血管（包括小动、静脉和毛细血管）的纤维素样坏死性血管炎.AAV的共同特征为血清中可检测到ANCA,肺和肾脏累及.根据2012年Chapel Hill会议[1]（CHCC）对血管炎分类标准的定义,ANCA相关性血管炎包括以下3类：显微镜下多血管炎（MPA）;肉芽肿性多血管炎（GPA）,原名为韦格纳肉芽肿;嗜酸细胞性肉芽肿性多血管炎（EGPA）,又名为Churg-Strauss综合征.由于AAV的临床表现多样且少有特异性,在临床工作中极易被漏诊或误诊,以致延误患者病情.     

有关抗中性粒细胞胞浆抗体相关性血管炎临床病理分型的争议

近十年来，人们开始认识到抗中性粒细胞胞浆抗体（ANCA）与某些类型坏死性血管炎之间存在着一定的联系“’。由于目前人们对各类系统性血管炎（包括ANCA相关性血管炎临床及病理生理过程）的认识尚处于初步积累阶段，所以对不同临床类型血管炎之间区别与联系仍不能达成一致的认识，特别是ANCA相关性血管炎临床病理分型存在较多的分歧”’。这些问题包括：①哪些传统分类类型的坏死性血管炎与ANC相关；②如何统一ANCA相关性坏死性血管炎分型的诊断命名烟怎样确定AN－CA相关性坏死性血管炎的诊断标准”‘。上述三个有争议的问题，实…     

抗中性粒细胞胞浆抗体相关的血管炎及肾小球肾炎

部分系统性血管炎及肾小球肾炎 (简称肾炎 )患者血清中可检测出ＡＮＣＡ (抗中性粒细胞胞浆抗体 ) ,目前已普遍认为ＡＮＣＡ与这些患者的血管炎及肾炎的发生有密切联系 ,因而称之为ＡＮＣＡ相关性血管炎或ＡＮＣＡ相关性肾炎。ＡＮＣＡ相关的血管炎绝大部分为小血管炎 (ｓｍａｌｌｖｅｓｓｅｌｖａｓｃｕｌｉｔｉｓ ,ＳＶＶ) ,因而也称为ＡＮＣＡ相关性小血管炎 (ＡＮＣＡ ＳＶＶ) ,主要包括微型多血管炎 (ＭＰＡ)、Ｗｅｇｅｎｅｒ肉芽肿及变应性肉芽肿性血管炎 (ＣＣＳ)。ＡＮＣＡ ＳＶＶ的肾脏受累较为常见 ,通常表现为急进性肾炎 (ＲＰＧ…     

抗中性粒细胞胞浆抗体相关性小血管炎诊断和治疗几点体会

抗中性粒细胞胞浆抗体（ANCA）相关小血管炎属系统性自身免疫性疾病，肾脏是常见的受累器官，随着我国ANCA检测的普及，该病的检出率也逐年增高，北京大学肾脏病研究所2003年新检出ANCA阳性患者138例，说明该病在我国并不少见，然而，国内对此病的诊治水平在不同地区之间还存在较大偏差，仍存在严重的误漏诊和治疗不当，下面介绍几点体会。     

抗中性粒细胞浆自身抗体在老年疾病检测中的临床意义

抗中性粒细胞浆自身抗体 (ANCA)是存在于系统性血管炎患者中的一类自身抗体 ,已经作为一种血清学标志物用于某些系统性血管炎及某些非血管炎性疾病的检测手段。本文旨在对老年患者 ANCA检查的临床意义进行评估 ,以便获得有益的启示。1　对象与方法1.1　 检测对象　为我院门诊与住院≥ 6 0岁患者 10 0例 ,各种疾病的诊断以最后确诊为准。健康对照组 4 7例 ,系北京东城区社区健康老年人 (男 13例 ,女 34例 ) ,年龄 6 5～ 75岁 (平均6 8.5岁 ) ,无器质性及免疫性疾病 ,符合国际 SENIEU R标准〔1〕。1.2 　 方法1.2 .1　 仪器及材料　 AN…     

New insight into the pathogenesis of vasculitis associated with antineutrophil cytoplasmic autoantibodies

PURPOSE OF REVIEW: To review the clinical, in-vitro and experimental animal model evidence for the pathogenicity of antineutrophil cytoplasmic autoantibodies. RECENT FINDINGS: Recent reports on the value of plasma exchange in the treatment of severe antineutrophil cytoplasmic autoantibody-associated glomerulonephritis support the importance of circulating antibodies. The correlation of antineutrophil cytoplasmic autoantibody positivity with renal disease in Churg-Strauss syndrome suggests that the vasculitic component of this syndrome may be induced by antineutrophil cytoplasmic autoantibodys but that other components have a different pathogenesis. In-vitro studies indicate that myeloperoxidase antineutrophil cytoplasmic autoantibody immunoglobulin G may be involved in pathogenesis not only by activating neutrophils but also by having pathophysiologic effects on the function of myeloperoxidase molecules. Findings using the mouse model of antineutrophil cytoplasmic autoantibody disease that is induced by intravenous injection of anti-myeloperoxidase indicate an unexpected role for the alternative pathway of complement activation in the pathogenesis of antineutrophil cytoplasmic autoantibody disease. This is substantiated by in-vitro observations showing that human myeloperoxidase antineutrophil cytoplasmic autoantibody immunoglobulin G and proteinase 3 antineutrophil cytoplasmic autoantibody immunoglobulin G cause neutrophils to release factors that activate complement. SUMMARY: Clinical, in-vitro and experimental animal model evidence continues to mount in favor of a pathogenic role of antineutrophil cytoplasmic autoantibody immunoglobulin G in the induction of vasculitis and glomerulonephritis. This emerging understanding of the pathogenic process may reveal novel and more effective approaches to treatment.     

Prevalence of antineutrophil cytoplasmic autoantibodies in patients with tuberculosis

OBJECTIVE: To determine the prevalence of antineutrophil cytoplasmic autoantibodies (ANCA) in sera of patients with tuberculosis compared with healthy control subjects and a group of patients with atopic asthma. METHODS: The presence of ANCA was examined in patients with tuberculosis, and in asthmatic patients and healthy subjects as control groups, by means of indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) to detect anti-proteinase 3 (PR3-ANCA) and antimyeloperoxidase (MPO-ANCA) antibodies. RESULTS: ANCA were present in 20 (44.4%) of 45 tuberculosis patients by IIF (16 c-ANCA, four p-ANCA) and in 18 (40%) patients by ELISA (15 PR3-ANCA, three MPO-ANCA). High odds ratios for ANCA positivity were observed for tuberculosis patients when compared with both control groups. ANCA results were not related to the category of tuberculosis, stage of disease, presence of concomitant diseases or pharmacotherapy. CONCLUSIONS: As many clinical similarities between tuberculosis and Wegener's granulomatosis exist, we propose that a positive ANCA test in patients living in countries with a high prevalence of tuberculosis must be carefully interpreted as indicative of systemic vasculitis, especially when no signs of extrapulmonary involvement occur.     

Disease associations and pathogenic role of antineutrophil cytoplasmic autoantibodies in vasculitis.

Antineutrophil cytoplasmic autoantibodies are a useful diagnostic serologic marker for a variety of well-known vasculitic syndromes, including Wegener's granulomatosis, polyarteritis nodosa (especially microscopic polyarteritis nodosa), Churg-Strauss syndrome, and pulmonary-renal syndrome with alveolar capillaritis. Although most patients with antineutrophil cytoplasmic autoantibody-associated disease have systemic disease, disease limited to one organ does occur, eg, isolated necrotizing glomerulonephritis, isolated respiratory tract disease, or isolated orbital disease. Antineutrophil cytoplasmic autoantibody titers may be useful in modulating treatment regimens. There is in vitro evidence that antineutrophil cytoplasmic autoantibodies are directly involved in the pathogenesis of antineutrophil cytoplasmic autoantibody-associated vasculitides.     

Inflammatory bowel diseases in Indo-Canadians with and without antineutrophil cytoplasmic autoantibodies.

A sequentially evaluated cohort of Indo-Canadians with either ulcerative colitis or Crohn's disease were prospectively examined for antineutrophil cytoplasmic autoantibodies (ANCA). Of 84 patients, 62 had ulcerative colitis and 22 had Crohn's disease. About one-third were born in Canada, and two-thirds were migrants from India or other countries, particularly East African nations. There was a disease-based and geographically based male predominance. The mean age of Canadian-born patients was significantly less than that of those born in other countries. Moreover, for migrants, the mean duration of residence in Canada before developing disease was 8.9 years for Crohn's disease patients and 13.5 years for ulcerative colitis patients. Moderate to severe disease was present; virtually all those with Crohn's disease had colonic involvement, and most of those with ulcerative colitis had extensive colonic disease. Overall, 40 of 84 (48%) were seropositive for ANCA, including a majority of those with ulcerative colitis but not Crohn's disease. In addition, eight had cytoplasmic ANCA, a reported seromarker for extensive colitis. Seropositive and seronegative patients were similar in age, sex, birth or duration of residence in Canada, site and severity of disease, familial history and complications, including pouchitis. This study supports the view that these diseases arise in individuals with a genetic predisposition following exposure to some, as yet unknown, environmental factor.     

Serial measurements of antineutrophil cytoplasmic autoantibodies in patients with systemic vasculitis.

PURPOSE: To assess the value of serial determinations of antineutrophil cytoplasmic autoantibodies (ANCA) for monitoring disease activity in patients with systemic vasculitis. PATIENTS AND METHODS: Forty-three patients with histologically proven vasculitis (21 with Wegener's granulomatosis, 17 with microscopic polyangiitis, and 5 with renal-limited vasculitis) were studied for a median follow-up of 22 months. Disease activity was prospectively assessed and quantified by the Birmingham Vasculitis Activity Score. A total of 347 sera were analyzed for ANCA determination. RESULTS: Relapses occurred in 23 (54%) of 43 patients. Diagnostic category (Wegener's granulomatosis vs micropolyangiitis and renal-limited vasculitis), severity of initial symptoms (mean vasculitis activity score, mean number of organs involved), and ANCA pattern [cytoplasmic-ANCA (c-ANCA) vs perinuclear-ANCA (p-ANCA)] did not significantly differ between relapsers and nonrelapsers. Lung involvement was more frequent at onset among relapsers [16 of 23 (70%) vs 6 of 20 (30%); P = 0.02]. Relapses were slightly, but not significantly, more frequent in patients with Wegener's granulomatosis or a c-ANCA pattern. The percentage of relapsers was greater in patients with persistently positive ANCA than in patients with negative or decreasing ANCA titers (86% vs 20%, P = 0.0001). However, the predictive value of an increase in ANCA titers for the occurrence of a subsequent relapse was only 28% (4 of 14) for c-ANCA, 12% (2 of 17) for anti-proteinase 3-ANCA, and 43% (6 of 14) for anti-myeloperoxidase-ANCA. An increase in ANCA occurred before or during relapse in 33% (10 of 30) of cases for c-ANCA/anti-proteinase 3 antibodies, and 73% (11 of 15) of cases for anti-myeloperoxidase antibodies. CONCLUSION: The persistence of ANCA positivity is strongly associated with relapses. However, an increase in ANCA titers has a poor value for the early prediction of a subsequent relapse and should not be used as a sole parameter for therapeutic intervention. In addition, our results suggest that serial anti-myeloperoxidase determination may be useful as a prognostic marker in patients who are p-ANCA positive.     

Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease

OBJECTIVES: Correct diagnosis of inflammatory bowel disease (IBD), especially the differentiation between Crohn's disease (CD) and ulcerative colitis (UC), is highly important toward treatment and prognosis. Serological markers are noninvasive diagnostic tools that could be of value in differentiating CD from UC, in cases of indeterminate colitis, and in the identification of subgroups in IBD. The aim of this study was to evaluate the diagnostic accuracy of perinuclear antineutrophil cytoplasmic (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) for IBD. METHODS: ASCA and pANCA were studied in a large cohort of consecutive IBD patients (n = 582: 407 CD, 147 UC, and 28 indeterminate colitis), patients with non-IBD diarrheal illnesses (n = 74), and healthy controls (n = 157). An indirect immunofluorescence technique and a standardized ELISA were performed for detection of pANCA and ASCA, respectively. RESULTS: Prevalence of ASCA and pANCA was high in CD patients (59.7%) and UC (49.7%) patients, respectively. Positivity for both markers was significantly lower in healthy and non-IBD controls. Accuracy data (sensitivity, specificity, PPV, and NPV, respectively) for differentiating IBD from controls are as follows: ASCA+: 60% (243/407), 91% (345/378), 88% (243/276), and 68% (345/509); pANCA+: 50% (73/147), 95% (605/638), 69% (73/106), and 89% (605/679); ASCA+/pANCA-: 56% (229/407), 94% (355/378), 91% (229/252), and 67% (355/533); and pANCA+/ASCA-: 44% (65/147), 97% (620/638), 78% (65/83), and 88% (620/702). CONCLUSIONS: Specificity of serological markers for IBD is high, but low sensitivity makes them less useful as diagnostic tests. The combination of tests is probably more powerful, although, clinical subgroups still need to be defined. The usefulness of these markers in indeterminate colitis needs to be studied prospectively.     

Seroprevalence and disease association of antineutrophil cytoplasmic autoantibodies and antigens in HIV infection

Summary This prospective study was designed to determine the role of antineutrophil cytoplasmic autoantibodies (ANCA) in HIV-infected patients. Immunofluorescence tests (IFT) and enzyme-linked immunosorbent assays (ELISA) were applied to sera of 199 consecutive outpatients. In the IFT 20% were positive. An atypical ANCA pattern was demonstrated in 67% of these, 33% revealed a perinuclear staining (pANCA). Specific ELISA revealed proteinase 3 (n=2), myeloperoxidase (n=1), lysozyme (n=2), lactoferrin (n=1), cathepsin G (n=1), and human leukocyte elastase (HLE, n=6). The target antigen remained unidentified in 26 patients. Perinuclear ANCA-positive patients showed atypical antigens in eight of 13 cases; all six patients with anti-HLE revealed a pANCA pattern. The antigens of atypical ANCA-positive patients remained unidentified in 21 of 26 (81%) cases. No signs of vasculitis were present in the ANCA-positive patients. ANCA are frequently found in the sera of HIV-positive patients. They bind to a variety of antigens. No correlation was found between ANCA positivity and autoimmune or opportunistic diseases.     

炎症性肠病患者血清中自身抗体检测的临床意义

目的研究抗酿酒酵母抗体(ASCA)和抗中性粒细胞胞浆抗体(pANCA)在炎症性肠病诊断与鉴别诊断中的意义。方法间接免疫荧光生物薄片法检测29例溃疡性结肠炎(UC)、34例克罗恩病(CD)及25例正常对照者血清中ASCA和pANCA的表达。结果pANCA在CD组、UC组和正常对照组中的阳性率分别为47.1%、69.0%和16.0%,UC组显著高于CD组(P<0.05)和正常对照组(P<0.05)。ASCA在上述3组中的阳性率分别为11.8%、58.6%和8.0%,UC组亦显著高于CD组(P<0.05)和正常对照组(P<0.05)。ASCA /pANCA-诊断CD的敏感性、特异性、阳性预测值分别是0、89.7%和0;pANCA /ASCA-诊断UC的敏感性、特异性和阳性预测值分别是20.7%、64.7%和33.3%。结论ASCA和pANCA阳性有利于炎症性肠病的诊断却不能敏感地筛选患者;ASCA和pANCA联合检测不能作为汉族UC和CD鉴别诊断的指标。     

Streptococcal viridans subacute bacterial endocarditis associated with antineutrophil cytoplasmic autoantibodies (ANCA)

We report an illustrative case of a 60-year-old man with Streptococcus viridans subacute bacterial endocarditis (SBE) and positive antineutrophil cytoplasmic autoantibodies (c-ANCA). C-ANCA positivity has been associated with a variety of rheumatic and infectious disease areas, but has been rarely associated with SBE. The patient had mitral valve prolapse with mitral regurgitation, and S viridans SBE developed after a dental procedure. Laboratory abnormalities included anemia, elevated erythrocyte sedimentation rate, positive rheumatoid factor, positive anticardiolipin antibody, positive lupus anticoagulant, and highly elevated c-ANCA level. We believe this is only the ninth reported case of S viridans SBE with a positive c-ANCA, and the third with mitral valve prolapse and vegetations.