丙基硫氧嘧啶引起抗中性粒细胞胞质抗体相关小血管炎并非药物性狼疮

目的 检测药物性狼疮（DIL）的血清学标志抗组蛋白抗体在抗中性粒细胞胞质抗体（ANCA）阳性的甲亢患者中的阳性率,并探讨丙基硫氧嘧啶（PITU）引起的ANCA相关小血管炎与DIL的关系。方法 以34例ANCA阳性的原发甲亢患者为研究对象,其中18例确诊为PITU引起的ANCA相关小血管炎;同时选取10例原发性ANCA相关小血管炎患者及10例初发未治疗的甲亢患者为对照,应用ELISA法检测抗组蛋白抗体。将我院确诊的PITU引起的ANCA相关小血管炎患者的临床资料与文献中抗甲状腺药物引起的DIL相比较。结果 所有原发性ANCA相关小血管炎的患者及初发未治疗的甲亢患者均未检测到抗组蛋白抗体;在34例PITU引起的ANCA阳性患者中仅1例（2．9％）抗组蛋白抗体阳性,此例患者为18例有血管炎临床表现中的1例（5．6％）。PITU引起的ANCA相关小血管炎不同于DIL,寡免疫复合物的坏死性新月体性肾炎及肺出血为前者的特征性表现。结论 PITU引起的ANCA相关小血管炎患者中抗组蛋白抗体的低发生率提示其与DIL可能不完全相同。     

显微镜型多血管炎肾活检病例的临床病理分析

目的探讨血清抗中性粒细胞胞质抗体（ANCA）及肾小球内有无免疫球蛋白（Ig）沉积在显微镜型多血管炎（MPA）肾活检病例中的病理诊断价值及其临床病理意义。方法34例MPA均为该系2000年1月至2007年3月7年间的就诊患者,其临床资料比较完整,后经肾穿刺活检而确诊者,分别对其血清ANCA阳性和阴性及肾小球内有无Ig沉积的临床病理特点进行比较。结果34例MPA患者,约1／5—1／2病例伴有各种肾外症状;经血清ANCA检测,阳性者26例（76．5％）;阴性者8例（23．5％）;其尿蛋白多呈轻一中度,呈肾病综合征者仅3例;肾功能减退者32例。经病理检查显示,24例为新月体性肾炎,8例为局灶节段性肾炎,其他类型者仅2例;伴肾血管坏死或内膜炎症7例,内膜增厚24例;伴间质炎性细胞浸润29例,其中21例伴有中性粒细胞浸润。经临床与病理比较分析,发现ANCA阳性组的新月体形成率显著高于ANCA阴性组（P〈0．05）;在26例ANCA阳性组病例中,肾小球Ig沉积者的尿蛋白定量显著高于无Ig沉积组（P〈0．05）,其中1例合并IgA肾病。结论对MPA的诊断有赖于对患者血清ANCA的检测和肾活检组织的病理学检查;ANCA是促进肾小球新月体形成的一个重要因素;Ig在肾小球内的沉积对患者蛋白尿的加重起促进作用。     

自身免疫肝病患者抗中性粒细胞胞浆抗体的检测及临床意义

探讨抗中性粒细胞胞浆抗体(anti-neutrophil cytoplastic antibodies,ANCA)对自身免疫肝病的临床意义。应用间接免疫荧光法和斑点法检测149例自身免疫性肝病患者[自身免疫性肝炎(autoimmune hepatitis,AIH)患者57例,原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)患者42例,不明原因肝损患者50例]的ANCA和抗可提取性核抗原抗体(extract-able nuclear antigen,ENA),进而用ELISA法分析60例ANCA阳性的自身免疫肝病患者的ANCA抗原谱。以200例健康献血员为正常对照。结果ANCA在AIH、PBC、不明原因肝损中的阳性率分别为81%、40%、30%,其中非典型性pANCA的阳性率依次为70%、40%、28%。AIH组与PBC组及AIH组与不明原因肝损组间非典型性pANCA的阳性率有显著性差异(P<0.01),但PBC组与不明原因肝损组间差异不显著(P>0.05)。各疾病组ANCA抗原谱如下:AIH组中,乳铁蛋白3%阳性,MPO 11%阳性,组织蛋白酶G和BPI的阳性率分别为11%、17%;PBC组中,弹性蛋白酶和组织蛋白酶G阳性率均为5%,BPI的阳性率为16%;不明原因肝损组中,BPI阳性率为17%。大多数自身免疫性肝病患者非典型性pANCA为阳性(28%~70%),且伴有特征性自身抗体。注重非典型性pANCA的检测对明确诊断自身免疫肝病及其分类有很大的帮助。     

类风湿关节炎患者血清炎性因子、ANCA水平与血管内皮损伤标志物的相关性分析

目的:探讨类风湿关节炎(RA)患者血清炎性因子及抗中性粒细胞胞浆抗体(ANCA)水平与血管内皮损伤的相关性。方法:106例RA患者,分为活动组(83例)和缓解组(23例),55例健康人群作为对照,采用ELISA检测各组血清炎性因子白介素-1β(IL-1β)、白介素-6(IL-6)、白介素-17(IL-17)、肿瘤坏死因子-α(TNF-α)及血管内皮损伤标志物-血管性血友病因子(vWF)、可溶性细胞间黏附分子-1(sI-CAM-1)及血管内皮黏附分子-1(sVCAM-1)水平;采用间接免疫荧光法(IIF)检测各组血清ANCA阳性率。比较各组上述指标水平差异,分析两组RA患者炎性因子水平、ANCA阳性率与血管内皮损伤标志物水平的相关性。结果:RA活动组IL-6、TNF-α、vWF、sICAM-1、sVCAM-1血清水平均高于对照组(P<0.05);RA缓解组IL-6、vWF水平均低于RA活动组(P<0.05),但vWF、sVCAM-1水平仍显著高于对照组(P<0.01);RA患者IL-6、IL-1β、IL-17与血管内皮损伤标志物有不同程度的相关性;RA患者活动组ANCA阳性率为32.5%,显著高于对照组(P<0.01);ANCA阳性患者vWF水平高于ANCA阴性患者(P<0.05)。结论:RA活动期患者存在较明显血管内皮损伤,这种损伤与高水平的炎性因子及ANCA阳性表达有关。     

肾脏疾病患者血清中ANCA的荧光模式及其意义

目的：进一步探讨肾脏疾病患者血清中抗中性粒细胞细胞质抗体(ANCA)的荧光模式及其意义。方法：应用间接免疫荧光(IIF)和ELISA方法检测了251例肾脏疾病患者血清中ANCA及其靶抗原。结果：在251例肾脏疾病患者中，ANCA阳性51例占20．3％，其中10例为cANCA阳性(10／251)；30例为cANCA阳性(30／251);11例为aANCA阳性(11／251)。结论：同时用IIF法和ELISA法检测ANCA，可以提高ANCA检出的阳性率；不同ANCA荧光模式与疾病的种类病情及预后密切相关；提高对不典型ANCA和pANCA伴ANA荧光模式的鉴别，有助于临床对血管炎和其它自身免疫性疾病的诊断。     

抗中性粒细胞胞浆抗体与抗核抗体谱联合检测对系统性红斑狼疮的临床意义

目的探讨系统性红斑狼疮(systemic lupus erythematosus,SLE)患者抗核抗体谱(antinuclear antibody spectrum,ANAs)与抗中性粒细胞胞浆抗体(antineutrophil cytoplasmic antibody,ANCA)联合检测的临床意义。方法采用间接免疫荧光法(IIF)和免疫印迹法(Western blot)检测120例SLE组患者、60例疾病对照组患者和20位健康人的ANCA和ANAs。用ELISA法检测验证ANCA阳性率,用SLE活动指数(SLEDAI)判断SLE活动性,分析ANCA、SLEDAI和ANAS之间的关系。结果在120例SLE患者中IIF法检测ANCA的阳性率为27.5(33/120),且均为核周型(perinuclear ANCA,pANCA)。用ELISA法验证全部ANCA阳性患者血清,阳性率为81.8(27/33),且均为髓过氧化物酶(myeloperoxidase,MPO)即为pANCA。ANCA阳性组SLEDAI评分>10分者(即SLE活动期)占81.4%与ANCA阴性组(36.5%)相比差异有显著性意义(P<0.01)。ANCA阳性组在血沉升高,补体C3、C4降低,肾脏损害、肺损害、关节肿痛等方面与ANCA阴性组比较差异具有显著性(P<0.01)。ANCA阳性率与抗ds-DNA抗体、抗Sm抗体、抗核小体抗体(AnuA)及抗核糖体P蛋白抗体(ARPA)阳性率呈正相关。结论联合检测ANCA和SLE的各项特异性自身抗体可能对SLE患者的早期发现、治疗、病情活动判断具有重要的意义。     

SLE患者检测血清ANCA的临床价值

目的 探讨抗中性粒细胞胞浆抗体（ANCA）在系统性红斑狼疮（SLE）患者中检测的临床意义.方法 通过间接免疫荧光法（IIF）检测57例SLE患者血清中的ANCA,对ANCA阳性血清采用免疫斑点法检测抗髓过氧化物酶（MPO）和蛋白酶3（PR3）抗体;同时以35例正常健康者作为对照组.回顾性分析SLE临床表现和实验室检查结果,SLE患者以SLE disease activity index（SLEDAI）分组（SLEDAI≥10为疾病活动组、〈10为疾病非活动组）,分析ANCA与其的相关性.结果 SLE患者中ANCA 阳性率为22.8%,其中核周型（pANCA）阳性12例,阳性率为 21.1%,胞浆型（cANCA）1例,阳性率为 1.7%,靶抗原均为非MPO、PR3;ANCA阳性组与ANCA阴性组SLE活动性存在显著性差异（P〈0.05）,ANCA阳性组患者的补体C3的下降、血沉（ESR）的增高、抗dsDNA抗体的阳性以及皮肤血管炎和肾脏损伤与ANCA阴性组比较,差异有统计学意义（P〈0.05）.结论 ANCA在SLE中有一定阳性检出率,对疾病活动性判断有一定的临床价值.     

ANCA阴性少免疫沉积型新月体性肾炎患者血清AECA与临床表现的关系研究

目的:探讨抗中性粒细胞胞浆抗体(ANCA)阴性少免疫沉积型新月体性肾炎患者血清抗内皮细胞抗体(AECA)表达情况,及其与临床表现的关系。方法:选取2010年至2015年在我院治疗的少免疫沉积型新月体性肾小球肾炎患者,其中ANCA阴性患者45例(观察组),ANCA阳性患者49例(对照组),采用Western blot检测各组患者血清AECA水平。结果:观察组平均年龄和伯明翰血管炎活动性评分(BVAS)分别为(41.08±9.43)岁和(15.03±3.82)分,明显低于对照组(P0.05);观察组出现发热、关节痛的比例分别为26.67%和13.33%,明显低于对照组(P0.05);观察组出现肾病综合征比例为48.89%,高于对照组(P0.05);观察组血清AECA阳性率为46.67%,明显低于对照组的81.63%(P0.05);观察组Ig G-AECA共识别7种蛋白,而对照组共识别11种蛋白,其中观察组抗90 k D抗体阳性率为13.33%(6/45),明显低于对照组的51.02%(25/49)(P0.05);观察组抗76 k D抗体阳性患者出现皮疹的比例为100%,明显高于阴性患者(P0.05),抗200 k D抗体阳性患者BVAS评分为(18.02±2.51)分,明显高于阴性患者(P0.05)。结论:ANCA阴性少免疫沉积型新月体性肾炎患者血清存在不同的AECA,可能与某些临床表现有关;ANCA阴性和阳性患者AECA有所不同,两者临床表现的差异可能与AECA的不同有关,需待进一步研究。     

ANCA相关性系统性小血管炎并肾损害患者肾组织血管内皮生长因子的表达

目的研究抗中性粒细胞胞质抗体(anti-neutrophil cytoplasmic antibodies,ANCA)相关性系统性小血管炎(ANCA associat-ed systemic vasculitis,AASV)并肾损害患者VEGF在肾组织表达及其与AASV活动与病理表现等的关系。方法采用超敏免疫组化两步法,对23例AASV并肾损害患者及5例对照组肾组织VEGF的水平进行检测,并结合临床资料及肾脏病理进行相关分析。结果 (1)AASV肾小球、肾小管VEGF表达较正常组升高(P0.01);并且无血管袢坏死病变组AASV肾小球VEGF表达高于有血管坏死病变组;部分患者肾间质浸润炎细胞有VEGF表达;(2)AASV肾小球VEGF表达与年龄呈正相关,相关系数为0.595(P0.05);肾小球VEGF表达与伯明翰血管炎活动指数(BVAS)呈负相关,相关系数为-0.454,差异有统计学意义(P0.05)。结论 (1)AASV并肾损害患者肾小球、肾小管VEGF的表达均增高;(2)AASV患者年龄越大,肾小球VEGF表达越多;(3)血管炎活动程度越高,肾小球VEGF表达越少。     

抗中性粒细胞胞浆抗体在ANCA相关血管炎患者中的临床意义

目的抗中性粒细胞胞浆抗体(anti-neutrophil cytoplasmic antibody,ANCA)两种类型,核周型(p-ANCA)及胞浆型(c-ANCA),比较p-ANCA阳性与c-ANCA阳性的ANCA相关血管炎(ANCA-associated vasculitis,AAV)患者临床特征、实验室指标及器官受累的差异。方法选取50例AAV患者,血清ANCA的检测采用间接免疫荧光法。根据ANCA血清分型分为p-ANCA阳性组与c-ANCA阳性组,同时检测两组患者血生化、尿常规、炎症指标、免疫指标;高分辨CT(high resolution CT,HRCT)评估AAV患者肺脏受累情况;AAV患者疾病活动度采用疾病累及范围指数(disease extent index,DEI)评分。结果 p-ANCA阳性组患者易伴发红细胞减少及肺间质疾病;c-ANCA阳性的患者年龄更小,病程更短,更易伴发镜下血尿、听力下降、鼻窦炎。两组的DEI评分无显著差异。结论 c-ANCA阳性患者临床表现重于p-ANCA阳性组患者,器官受累更重,预后更差。     

Pauci-immune crescentic glomerulonephritis

Pauci-immune crescentic glomerulonephritis (PICGN) is a rapidly progressive condition leading to renal failure within days or weeks and is potentially life threatening. Majority of these patients have clinical or pathological evidence of systemic vasculitis. PICGN may occur as renal limited disease or as a component of systemic necrotising small vessel vasculitis. Majority of these cases are attributed to Wegener's granulomatosis (WG), microscopic polyangitis (MPA) or Churg Strauss syndrome (CSS). Renal involvement is encountered in 80 to 90% cases of WG and MPA and in about 45% cases of CSS. Approximately 80 to 90% patients of untreated WG or MPA and about 60% cases of CSS are positive for anti-neutrophilic cytoplasmic antibodies (ANCA). These diseases are therefore also called as ANCA-associated vasculitis. Serial ANCA measurements provide useful information on disease activity. Renal transplant should be avoided in patients with clinical evidence of active vasculitis. Even though the treatment with oral corticosteroids and i.v. or oral cyclophosphamide results in complete long term remission in 70 to 75% patients, relapse occurs in >25% cases within a mean period of 18 months after cessation of therapy. Prognosis of untreated ANCA-associated PICGN is poor.     

丙硫氧嘧啶引起抗中性粒细胞胞浆抗体相关小血管炎6例临床分析

目的：提高临床对丙硫氧嘧啶（PTU）引起抗中性粒细胞胞浆抗体（ANCA）相关小血管炎的认识。方法：分析近年诊治的6例PTU引起ANCA相关小血管炎患者的临床表现、实验室及病理检查、治疗及随访情况。结果：6例患者服用PTU至出现小血管炎症状的时间不等，2月-7年，小血管炎表现也可在PTU停药后出现，临床表现不一，轻者仅皮肤、关节、肌肉受累，重者可出现重度贫血、肺出血、肾受累，抗MPO-ANCA均阳性。停用PTU及激素、免疫抑制剂治疗后病情好转，ANCA滴度下降或转阴。结论：PTU可引起ANCA相关小血管炎，部分可引起肺出血及肾损害，临床应予重视，及时停用PTU及相应治疗大多预后较好。     

Immune regulatory mechanisms in ANCA-associated vasculitides

A group of primary vasculitides is associated with the presence of anti-neutrophil cytoplasmic autoantibodies (ANCA). In these diseases, the contribution of ANCA to disease pathogenesis has been studied extensively. Also, in patients with ANCA-associated vasculitides, the T lymphocyte compartment is dysregulated, as aberrant distribution and function of T cell subsets has been shown. In this review we will discuss the putative role of T lymphocytes in inflammation and granuloma formation, as well as the involvement of B cell compartments in the pathophysiology of ANCA-associated vasculitis.     

免疫印迹技术检测抗中性粒细胞胞浆抗体的应用研究

用免疫印迹技术（ＩＢＴ）检测了１０１例不同原因的血管炎、ＳＬＥ和类风湿性关节炎（ＲＡ）患者血清中的抗中性粒细胞胞浆抗体（ＡＮＣＡ），ＡＮＣＡ与凝胶电泳时２９ＫＤａ处的中性粒细胞胞浆抗原形成一条明显的沉淀带。韦格纳氏／多血管炎组患者的阳性率为５４．５％（６／１１例），显著高于其他血管炎、ＳＬＥ和ＲＡ患者的１４．２％（３／２１例），４．２％（２／４８例）和０％（０／２１例）。３５份正常人血清全呈阴性。用ＡＮＣＡ阳性血清作用于中性粒细胞，在间接免疫荧光检测时均呈胞浆型（Ｃ－ＡＮ－ＣＡ）。此法特异、简便、易于推广应用，有助于血管炎的诊断。     

Antineutrophil cytoplasmic antibodies (ANCA)

Antineutrophil cytoplasmic antibodies (ANCA) are a sensitive and specific marker for ANCA-associated systemic vasculitis. Using indirect immunofluorescence on ethanol-fixed neutrophils, two major fluoroscopic patterns can be recognised: a diffuse cytoplasmic staining (C-ANCA), and a perinuclear/nuclear staining (P-ANCA). In patients with vasculitis, more of 90% of C-ANCA are directed against proteinase 3 (PR3-ANCA) whereas approximately 80–90% of P-ANCA recognise myelperoxidase (MPO-ANCA). Although C-ANCA (PR3-ANCA) is preferentially associated with Wegener's granulomatosis (WG), and P-ANCA (MPO-ANCA) with microscopic polyangiitis (MPA), idiopathic necrotising crescentic glomerulonephritis (iNCGN) and Churg-Strauss syndrome (CSS), there is not absolute specificity. Between 10–20% of patients with classical WG show P-ANCA (MPO-ANCA), and even a larger percentage of patients with MPA or CSS have C-ANCA (PR3-ANCA). Furthermore, it should be stressed that approximately 10–20% of patients with WG or MPA (and 40–50% of cases of CSS) have negative assay for ANCA. The best diagnostic performance is obtained when indirect immunofluorescence is combined with PR3 and MPO-specific ELISAs. ANCA with different and unknown antigen specificity are found in a variety of conditions other than AASV, including inflammatory bowel diseases, other autoimmune diseases, and infections where their clinical significance is unclear.

ANCA levels are useful to monitor disease activity but should not be used by themselves to guide treatment. A significant increase in ANCA titres, or the reappearance of ANCA, should alert the clinicians and lead to a stricter patient control.     

Antineutrophil cytoplasmic antibodies (ANCA)

Antineutrophil cytoplasmic antibodies (ANCA) are a sensitive and specific marker for ANCA-associated systemic vasculitis. Using indirect immunofluorescence on ethanol-fixed neutrophils, two major fluoroscopic patterns can be recognised: a diffuse cytoplasmic staining (C-ANCA), and a perinuclear/nuclear staining (P-ANCA). In patients with vasculitis, more of 90% of C-ANCA are directed against proteinase 3 (PR3-ANCA) whereas approximately 80-90% of P-ANCA recognise myelperoxidase (MPO-ANCA). Although C-ANCA (PR3-ANCA) is preferentially associated with Wegener's granulomatosis (WG), and P-ANCA (MPO-ANCA) with microscopic polyangiitis (MPA), idiopathic necrotising crescentic glomerulonephritis (iNCGN) and Churg-Strauss syndrome (CSS), there is not absolute specificity. Between 10-20% of patients with classical WG show P-ANCA (MPO-ANCA), and even a larger percentage of patients with MPA or CSS have C-ANCA (PR3-ANCA). Furthermore, it should be stressed that approximately 10-20% of patients with WG or MPA (and 40-50% of cases of CSS) have negative assay for ANCA. The best diagnostic performance is obtained when indirect immunofluorescence is combined with PR3 and MPO-specific ELISAs. ANCA with different and unknown antigen specificity are found in a variety of conditions other than AASV, including inflammatory bowel diseases, other autoimmune diseases, and infections where their clinical significance is unclear. ANCA levels are useful to monitor disease activity but should not be used by themselves to guide treatment. A significant increase in ANCA titres, or the reappearance of ANCA, should alert the clinicians and lead to a stricter patient control.     

2020 international consensus on ANCA testing beyond systemic vasculitis

This document follows up on a 2017 revised international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in granulomatosis with polyangiitis and microscopic polyangiitis and focuses on the clinical and diagnostic value of ANCA detection in patients with connective tissue diseases, idiopathic interstitial pneumonia, autoimmune liver diseases, inflammatory bowel diseases, anti-glomerular basement membrane (GBM) disease, infections, malignancy, and during drug treatment. Current evidence suggests that in certain settings beyond systemic vasculitis, ANCA may have clinical, pathogenic and/or diagnostic relevance. Antigen-specific ANCA targeting proteinase-3 and myeloperoxidase should be tested by solid phase immunoassays in any patient with clinical features suggesting ANCA-associated vasculitis and in all patients with anti-GBM disease, idiopathic interstitial pneumonia, and infective endocarditis associated with nephritis, whereas in patients with other aforementioned disorders routine ANCA testing is not recommended. Among patients with autoimmune liver diseases or inflammatory bowel diseases, ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1 who do not have conventional autoantibodies or in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn’s disease. In these cases, ANCA should be tested by indirect immunofluorescence as the target antigens are not yet well characterized. Many questions concerning the optimal use of ANCA testing in patients without ANCA-associated vasculitis remain to be answered.