抗中性粒细胞胞浆抗体在自身免疫病中检测的临床意义

１９８２年Ｄａｖｉｅｓ等用间接免疫荧光法（ＩＦ）首先在坏死性肾小球肾炎患者血清中发现了抗中性粒细胞胞浆抗体（ＡＮＣＡ）〔１〕，后来发现它是韦格纳氏肉芽肿（ＷＧ）病情活动的标志〔２〕。根据抗原的成分不同又分为胞浆ＡＮＣＡ（ｃＡＮＣＡ）和核周ＡＮＣＡ（...     

炎症性肠病相关抗中性粒细胞胞浆抗体

抗中性粒细胞胞浆抗体（ＡＮＣＡ）已发现与炎症性肠病关系密切。本文就近年在炎症性肠病相关ＡＮＣＡ的检测方法、临床意义、靶抗原及其在炎症性肠病发病机理中的作用等方面的研究进展作一综述。     

溃疡性结肠炎与抗中性粒细胞胞浆自身抗体

溃疡性结肠炎病人血清中存在不典型抗中性粒细胞胞浆自身抗体，该抗体的靶抗原可能与β－葡萄糖醛酸酶、溶菌酶、组蛋白酶－Ｇ和乳铁蛋白等有关。它与溃疡性结肠炎的发病关系并不密切，但可以作为溃疡性结肠炎的血清学和遗传学标记。     

SLE与抗中性粒细胞胞浆抗体的检测

抗中性粒细胞胞浆抗体 (ANCA)是存在于血液循环中一种抗体 [1 ] ,1982年首次在坏死性肾小球肾炎患者中发现。检测抗中性粒细胞胞浆抗体是诊断系统性血管炎的一种有效的方法。近年还逐渐发现一些结缔组织病也存在该种抗体。但是 ANCA在 SL E诊断中的意义至今还有争议 [2 ] 。本文采用间接免疫荧光法技术 (IIF)对 SL E患者血清进行 ANCA的检测 ,用以探讨该抗体对 SL E临床意义。1　材料与方法1.1　临床资料　我院系统性红斑狼疮 (SL E)患者 ,70例 ,女6 0例 ,男 10例 ,年龄 13～ 49岁。诊断均符合 1982年美国风湿病协会修订的 SL E…     

抗中性粒细胞胞浆抗体检测在类风湿性关节炎并发新月体性肾小球肾炎中的临床意义

目的:探讨类风湿性关节炎(rheumatoid arthritis,RA)并发新月体性肾小球肾炎(crescenticglomerulonephritis,CrGN)抗中性粒细胞胞浆抗体(antineutrophil cytoplasmic antibody,ANCA)检测的临床意义。方法:回顾性分析2000年1月至2010年12月萍乡市人民医院诊治的5例RA并发CrGN患者(RA并发CrGN组)、86例RA(RA组)和16例ANCA相关性小血管炎患者(ANCA相关性小血管炎组)的ANCA检测结果及临床病理特征。结果:RA并发CrGN组中,5例都为中年妇女,且具有7~14年的RA病龄,最初的临床症状都为血尿,从血尿发展到具有明显组织病变平均时间为17个月,ANCA检测均为核周型ANCA(pANCA)阳性,靶抗原为髓过氧化物酶(myeloperoxidase,MPO),被检肾小球平均有31%形成新月体,同时也存在肾小球硬化和间质性纤维化等症状;RA组ANCA检测均为阴性,ANCA相关性小血管炎组ANCA检测阳性,阳性率为87.5%(14/16),且均为pANCA;与ANCA相关性小血管炎组相比,RA并发CrGN组确诊年龄明显小于前者(P<0.05)。结论:RA并发CrGN发病年龄趋于年轻化,疾病的发展过程趋于漫长并且伴随轻微肾功能损伤,ANCA检测对RA并发CrGN患者早期发现、治疗具有重要的意义。     

抗中性粒细胞胞浆抗体的检测方法及临床意义

抗中性粒细胞胞浆抗体ＡＮＣＡ是一种针对中性粒细胞和单核细胞胞浆成分的自身抗体１９８２年Ｂａｖｉｅｓ等在少数非典型血管炎患者中发现。目前认为ＡＮＣＡ与某些疾病尤其是自身免疫性病相关并将其作为诊断系统性血管炎等相关疾病的血清学标志物。其主要检测方法为免疫荧光染色。应用间接免疫荧光法ＩＩＦ可将ＡＮＣＡ分为Ｃ－ＡＮＣＡ和Ｐ－ＡＮＣＡ两类。Ｃ－ＡＮＣＡ的靶抗原主要为蛋白酶３ＰＲ－３相对分子质量Ｍｒ为２９０００Ｐ－ＡＮＣＡ针对的靶抗原主要为髓过氧化物酶ＭＰＯＭｒ为１２００００。…     

抗中性粒细胞胞浆抗体检测在溃疡性结肠炎诊断中的意义

溃疡性结肠炎（ulcerative colitis,UC）是一种以腹痛、腹泻、黏液脓血便为主要临床表现的慢性非特异溃疡性结肠炎性病变。因其症状缺乏特异性,临床上需与克罗恩病（crohn disease,CD）、肠易激综合征（irritable bowel disease,IBS）、感染性肠病、     

溃疡性强肠炎与抗中性粒细胞胞浆自身抗体

溃疡性结肠炎病人血清中存在不典型抗中性业细胞胞浆浆自身抗体，该抗体的靶抗原可能与β－葡萄糖醛酸酶、溶菌酶、组蛋白酶－Ｇ和乳腺蛋白等有关，它与溃疡性结肠炎的发病关系并不密切但可以作为溃疡性结肠炎的血清学和遗传学标记。     

抗中性粒细胞胞浆抗体相关性血管炎的胸部CT表现

目的:探讨抗中性粒细胞胞浆抗体(antineutrophil cytoplasmic antibodies,ANCA)相关性血管炎(ANCA-associated small vessel vasculitis,AASV)的胸部CT表现.方法:回顾性分析2012年1月至2016年12月在苏州大学附属第一医院经血清学确诊的25例AASV患者的胸部CT表现.结果:25例患者中,男11例,女14例,年龄32～79岁(平均62)岁,其中胞浆型抗中性粒细胞胞浆抗体(cytoplasm antineutrophil cytoplasmic antibodies,c-ANCA)阳性5例,核周型抗中性粒细胞胞浆抗体(peripheral antineutrophil cytoplasmic antibodies,p-ANCA)阳性20例.胸部CT主要表现为间质性肺炎19例,斑片状磨玻璃影10例,结节及肿块7例,胸膜增厚5例,肺气肿肺大疱4例,支气管扩张4例,支气管充气征3例,空洞3例,胸腔积液3例,蜂窝肺1例,纵膈淋巴结肿大1例.在主要的3个影像学表现中,p-ANCA阳性患者中间质性肺炎的比例较高,较c-ANCA阳性患者而言,差异具有统计学意义(P<0.05),而斑片状磨玻璃影、结节及肿块两者比较差异并无统计学意义(P>0.05).结论:AASV患者胸部CT表现多样,以间质性肺炎、斑片状磨玻璃影、结节及肿块为主,p-ANCA阳性患者更易合并间质性肺炎.     

Antineutrophil cytoplasmic antibodies and other immunologic abnormalities in patients with habitual abortion.

PROBLEM: The immunologic mechanisms of pregnancy loss in habitual aborters with antiphospholipid and antinuclear antibodies have not been fully clarified. The possible association of antineutrophil cytoplasmic antibodies (ANCAs) with recurrent miscarriage was examined. METHOD OF STUDY: In a prospective, controlled trial of 59 women with recurrent abortion, the prevalence of pANCA (antimyeloperoxidase), cANCA (antiproteinase-3), and immunoserologic abnormalities of systemic lupus erythematosus (SLE) anti double-stranded DNA, anti-SSA, anti-SSB, anti-U1RNP, anti-Sm, anticardiolipin and antinuclear antibodies, LE-cell, lupus anticoagulant, and complement-3 were investigated. RESULTS: pANCA occurred in 2, and cANCA in 6 of 59 case patients, but neither was observed in the controls (P = 0.09 for cANCA). cANCA levels were significantly higher in patients than in controls (P = 0.028). Six recurrent aborters were identified as having a group of immunoserologic abnormalities characteristic of SLE. CONCLUSIONS: Immunologic mechanisms detectable in SLE may operate in a subgroup of habitual aborters with suspected immunologic cause. ANCAs occur more frequently in patients with recurrent miscarriage than in controls.     

Correlations of anti-dsDNA and anti-ribosomal P autoantibodies with lupus nephritis

Patients with systemic lupus erythematosus, with and without nephritis, were studied for their serological profiles. Patients were stratified into two groups defined by the presence or the absence of precipitating antibodies to ribosomal P proteins. It was found that 27 patients were positive for anti-P precipitins and the remaining 34 patients were studied for the presence of lesser amounts of anti-P antibodies by Western blot and ELISA tests. The nephritic patients were characterized most frequently by the presence of both autoantibodies to dsDNA and the ribosomal P proteins. In the group with anti-P precipitins, anti-dsDNA titers were much higher in the patients with nephritis than in those without nephritis. Thus, over a wide range of anti-ribosomal P antibody concentrations, the mutual occurrence of anti-P antibodies with anti-dsDNA antibodies was strongly associated with lupus nephritis.     

单核细胞骨调素的表达水平与狼疮肾炎

目的：研究骨调素（OPN）在狼疮性肾损害中的作用。方法：采用酶联免疫吸附试验（Ⅱ届A）检测了90例系统性红斑狼疮（SLE）患者、15例非SLE肾损害患者及30例对照血浆OPN的水平，应用半定量RT-PCR方法，测定以上各组外周血单个核细胞（PBMCs）OPN的表达。结果：狼疮处于疾病活动时PBMCs OPN mRNA表达上调，尤其是狼疮肾炎活动组患者PBMCs OPN mRNA表达增加最为显著（P〈0．01），PBMCs OPN mRNA表达不仅与总狼疮疾病活动指数评分呈正相关（r=0．532，P〈0．001），而且与狼疮疾病活动指数肾评分呈正相关（r=0．584，P〈0．001），而非狼疮肾脏疾病组仅低水平表达，与正常对照组水平相近似（P〉0．05）。狼疮活动组血清OPN水平较非活动组及正常对照组均明显升高（P〈0．01），但活动性狼疮肾炎组与无肾损伤组之间血清OPN水平的差异无显著性（P〉0．05）。结论：狼疮处于疾病活动时PBMCs OPN mRNA表达上调，并与狼疮肾炎的疾病活动情况密切相关。     

Prevalence of antineutrophil cytoplasmic antibodies during treatment with benzylthiouracil

Background

Drug induced antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis is a rare complication associated especially with propylthiouracil (PTU). Prevalence of ANCA in patients receiving PTU is well established. Few cases of vasculitis were also reported with benzylthiouracil (BTU). The objective of this study is to clarify the prevalence of ANCA in patients receiving BTU.

Methods

ANCA were investigated by indirect immunofluoresence and enzyme linked immunosorbant assay in 159 patients with Graves’ disease (86 untreated and 73 treated with BTU).

Results

ANCA were positive in three (3.5%) untreated patients and 27 (37%) treated ones. Titres of ANCA varied between 1:20 and 1:200. There was a significant association between BTU treatment and ANCA (p < 0.001). ANCA were directed against myeloperoxidase (MPO) in 28 (93.3%) patients. Median treatment duration was 24 months (ranges 0.5 to 144 months). There was no significant association between treatment duration and ANCA. Vasculitis was found in two (2.7%) treated patients. One patient has developed isolated cutaneous vasculitis and the other one a pulmonary vasculitis with diffuse alveolar haemorrhage.

Conclusion

BTU therapy is characterised by a high prevalence of ANCA mainly but not exclusively directed against MPO. However, vasculitis remains a rare complication.     

Antineutrophil cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibodies, and specific IgE to food allergens in children with inflammatory bowel diseases

Differential diagnosis between ulcerative colitis (UC) and Crohn's disease (CD) is difficult in the initial phases in pediatric patients with inflammatory bowel diseases (IBD). This study was performed to determine the significance of anti-neutrophil cytoplasmic antibodies (ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) in IBD. ANCA were specified with regard to their antigenic specifity, significance to the diagnosis, and correlation of titer with the disease activity. The occurrence of food allergy was questioned, too. Serum samples from 44 children with UC (n = 23) or CD (n = 21) and from disease-control children (coeliac disease, n = 21) were analyzed for IgG ANCA, ANCA target antigens, IgA and IgG ASCA, and IgE to food allergens. Results show that ANCA occur more frequently in UC than in CD and disease-control (74, 24, and 10%, respectively). The presence of ANCA does not reflect disease activity. Antigenic specificity does not differ in any group. IgA-ASCA are found more often in patients with CD (76% versus 17% in UC). The testing for both ANCA and ASCA enabled clear-cut differential diagnosis between UC and CD based on the high specificity (ANCA+ ASCA- 92.5% for UC, ANCA- ASCA+ 93.2% for CD). Specific IgE to food allergens were found in 8.7, 14.3, and 23.8% of patients with UC, CD, and coeliac disease, respectively. We conclude that combined testing of ANCA and ASCA represents a valuable tool in the differential diagnosis between UC and CD in pediatric patients, minimizing invasive diagnostic procedures. Monitoring of ANCA, its specificity, and titer determination does not bring more information. Testing for specific IgE to food allergens may be considered in individual patients.     

Uveitis and anti-neutrophil cytoplasmic antibodies.

Serum samples of 485 uveitis patients were screened for the presence of anti-neutrophil cytoplasmic antibodies using a standardized immunofluorescence test (IIF) on neutrophil granulocytes. Seventeen of these sera contained cytoplasmic (C)-ANCA antibodies, while two of the sera contained perinuclear (P)-ANCA antibodies (both antinuclear antibody (ANA)-positive, one anti-myeloperoxidase (MPO)-positive). None of the C-ANCA-positive sera reacted with proteinase-3 in ELISA using a highly purified proteinase-3 preparation. Four C-ANCA and one P-ANCA-positive serum reacted with MPO. The majority of the sera did react with azurophilic granules in ELISA. The implication of these results is that in patients with uveitis a positive C-ANCA test is not diagnostic for Wegener's granulomatosis, but is most probably caused by the presence of autoantibodies against as yet unknown constituents of azurophilic granules.     

环磷酰胺治疗增殖性狼疮性肾炎的Meta分析

目的评价环磷酰胺（CTX）治疗增殖性狼疮性肾炎（PLN）的疗效和安全性。方法检索Cochrane图书馆、PubMed、EMBASE、中国生物医学文献数据库、中国期刊全文数据库、维普数据库,检索时间均从建库至2010年11月30日,获得CTX治疗PLN的相关RCT文献。由3名系统评价员进行资料提取和文献偏倚评价。依据随机方法、分配隐藏、盲法、结果数据的完整性、选择性报告研究结果和其他偏倚来源进行文献偏倚评价。计数资料采用OR值及其95%CI表示;计量资料采用加权均数差（WMD）或标准化均数差（SMD）及其95%CI表示。对同质资料采用RevMan5.0软件进行Meta分析。结果共检索到符合条件的文献1253篇,符合纳入标准的37篇RCT文献（n=2296）进入Meta分析。19篇文献采用了正确的随机化方法,6篇文献采用了分配隐藏,4篇文献采用盲法,纳入文献均未提及是否选择性报道结果,均未报告其他偏倚来源。Meta分析结果显示：①大剂量CTX组病死率（OR=0.24,95%CI：0.06～0.89）及SCr倍增发生率（OR=0.38,95%CI：0.15～0.96）显著低于小剂量CTX组。②CTX/糖皮质激素联合治疗组终末期肾病（ESRD）（OR=0.56,95%CI：0.31～1.00）、SCr倍增发生率（OR=0.46,95%CI：0.26～0.81）及复发率（OR=0.18,95%CI：0.04～0.82）显著低于单用糖皮质激素组;肾功能稳定（OR=1.94,95%CI：1.15～3.28）、带状疱疹（OR=2.63,95%CI：1.21～5.74）及闭经（OR=3.74,95%CI：1.85～7.57）发生率显著高于单用糖皮质激素组。③CTX组带状疱疹（OR=3.92,95%CI：1.20～12.86）及闭经（OR=4.04,95%CI：1.66～9.82）发生率显著高于硫唑嘌呤组。④CTX/糖皮质激素联合治疗组完全缓解率（OR=0.46,95%CI：0.28～0.76）及总缓解率（OR=0.66,95%CI：0.48～0.91）显著低于霉酚酸酯/糖皮质激素联合治疗组,闭经（OR=6.13,95%CI：1.98～18.94）及WBC减少（OR=2.30,95%CI：1.41～3.76）发生率显著高于霉酚酸酯/糖皮质激素联合治疗组。⑤CTX/硫唑嘌呤联合治疗组闭经（OR=4.92,95%CI：1.63～14.88）及WBC减少（OR=8.64,95%CI：1.92～38.96）发生率显著高于霉酚酸酯组。⑥CTX/糖皮质激素联合治疗较环孢素/糖皮质激素联合治疗,可显著提高24h尿蛋白定量（MD=0.26,95%CI：0.11～0.41）、50%补体溶血单位（MD=6.20,95%CI：5.17～7.23）、C3（MD=16.12,95%CI：13.38～18.87）及CCr（MD=12.04,95%CI：5.04～19.04）水平;可显著降低抗双链DNA抗体水平（MD=-2.20,95%CI：-2.86～-1.55）、生长速度（MD=-5.50,95%CI：-6.07～-4.93）及生长速度标准差（MD=-1.00,95%CI：-1.24～-0.76）。结论 CTX/糖皮质激素联合治疗PLN的疗效要优于单用糖皮质激素,不良反应发生率高于单用糖皮质激素;CTX/糖皮质激素联合治疗PLN的疗效及保护肾功能不如霉酚酸酯/糖皮质激素联合治疗,不良反应发生率高于霉酚酸酯/糖皮质激素联合治疗;CTX/硫唑嘌呤联合治疗PLN的疗效与霉酚酸酯相似,不良反应发生率高于霉酚酸酯;CTX治疗PLN的疗效与硫唑嘌呤相似,不良反应发生率高于硫唑嘌呤;CTX应选择合适的治疗剂量及最短的治疗时间来减少其不良反应。     

Urinary TWEAK and the activity of lupus nephritis

The TNF superfamily cytokine TWEAK induces mesangial cells, podocytes, and endothelial cells to secrete pro-inflammatory chemokines including MCP-1, IP-10 and RANTES, which are crucial in the pathogenesis of lupus nephritis (LN). As TWEAK regulates the secretion of these inflammatory mediators, we studied whether urinary TWEAK (uTWEAK) levels might be predictive and/or diagnostic in LN. In a cross-sectional study of a large, multi-center cohort of systemic lupus erythematosus (SLE) patients, uTWEAK levels were higher in patients with active as compared to never or non-active nephritis (median (IQR): 16.3 (9.9-23.0) versus 5.5 (2.3-16.8) pg/mg creatinine, p=0.001), and levels of uTWEAK correlated with the renal SLE disease activity index (rSLEDAI) score (r=0.405, p<0.001). uTWEAK levels were higher in patients undergoing a flare as compared to patients with chronic stable disease (11.1 (8.1-18.2) and 5.2 (2.3-15.3) pg/mg creatinine, respectively; p=0.036). Moreover, uTWEAK levels were significantly higher in patients undergoing a renal flare, as opposed to a non-renal flare (12.4 (9.1-18.2) and 5.2 (3.0-11.9) pg/mg creatinine, respectively; p=0.029). An accurate, non-invasive method to repeatedly assess kidney disease in lupus would be very helpful in managing these often challenging patients. Our study indicates that urinary TWEAK levels may be useful as a novel biomarker in LN.     

Anti-alpha-actinin antibodies are part of the anti-cell membrane antibody spectrum that characterize patients with lupus nephritis

Anti-membrane autoantibodies (MbA) have been reported in sera from patients with lupus nephritis (LN) but the targets of the MbA remain to be explored, which is the aim of the current study. Sera were collected from 40 patients with LN determined by renal biopsy, and from 30 systemic lupus erythematosus (SLE) patients without clinical evidence of LN. Thirty autoimmune disease control patients (rheumatoid arthritis, Sjögren's syndrome and systemic sclerosis), and 30 healthy controls were also included. Using flow cytometry, the presence of anti-MbA was explored revealing that IgG anti-MbA positivity was associated with LN (62.5% vs 13.3%) when compared to non-LN SLE patients, autoimmune disease patients (6.7%) and healthy controls (0%). Next, using purified plasma membrane fractions from human embryonic kidney (HEK) cells, the more prominent targets and their occurrence rates were located at 50 kDa, 60/65 kDa, 90 kDa, 110 kDa, 180 kDa and 220 kDa. Alpha-actinin (110 kDa) autoAb was characterized as a major target in LN patients positive for anti-MbA, and anti-MbA binding activity was reduced (36.9 ± 13.7%) in the presence of α-actinin. Laminin (200 kDa) was also characterized as a minor target, which was not the case for annexin A2 (36 kDa). Finally, anti-MbA IgG subclass analysis indicated a predominance of IgG2. In conclusion, IgG anti-MbA were detected at high levels in LN patients supporting a primary pathogenic role for anti-MbA and anti-MbA/α-actinin+ in LN that needs further research.