系统性红斑狼疮患者中抗中性粒细胞胞质抗体和细胞因子的关系

目的　探讨抗中性粒细胞胞质抗体 (ANCA)与系统性红斑狼疮 (SLE)血管炎临床特点的关系。检测SLE血管炎患者肿瘤坏死因子 (TNF) α、白细胞介素 (IL) 6等细胞因子的血清水平 ,探讨ANCA与SLE血管炎细胞因子的关系。方法　 6 0例SLE活动期患者和 30名正常对照组均通过间接免疫荧光法 (IIF)检测ANCA与酶联免疫吸附试验 (ELISA)检测抗髓过氧化物酶 (MPO)抗体 (即MPO ANCA) ,观察两组ANCA与抗MPO抗体的阳性率。通过ELISA法检测 30例SLE活动期患者和 30名健康对照者 ,外周血TNT α、白细胞介素 (IL) 6水平。结果　 6 0例SLE患者 1 5例ANCA阳性 ,均为核周型抗中性粒细胞胞质抗体 (pANCA) ,阳性率为 2 5 % ,抗MPO抗体 8例阳性(IIF法ANCA均阳性 ) ,阳性率为 1 3 3% ,健康对照组ANCA及抗MPO抗体均为阴性。病程超过 1年 ,伴有肾炎、浆膜炎、皮肤血管炎组 ,ANCA阳性率高 ,与无相应特点的对照组差异均有显著性 (P <0 0 5 ) ;有关节炎比无关节炎组ANCA阳性率高 (P =0 0 5 )。SLE活动期患者与对照组相比 :SLE组TNF α、IL 6水平较高 (P <0 0 5 )。抗MPO抗体阳性组与抗MPO抗体阴性组相比 :TNF α、IL 6水平升高 ,两组差异有显著性 (P <0 0 5 )。结论　部分SLE病人血清中可检测到 pANCA及抗MPO抗体 ,pANCA与SLE某些     

丙硫氧嘧啶导致的抗中性粒细胞胞浆抗体相关性血管炎的临床研究

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）相关性血管炎的认识。方法分析近年诊治的6例刖引起ANCA相关小血管炎患者的临床表现、实验室检查、病理检查、治疗及随访情况,结合文献及联系显微镜下多血管炎（MPA）的临床特点进行分析。结果6例服用PITU的患者出现肺、肾、皮肤及消化道等多脏器受累,其中5例抗MPO—ANCA阳性,1例抗PR3-ANCA阳性。停用PTU,使用激素或联合免疫抑制剂治疗后病情好转,ANCA转阴。结论刑可引起ANCA相关小血管炎,尽管ANCA滴度高,但致病性较弱,及时停用PITU及给予相应治疗,预后较好。     

426例抗中性粒细胞胞浆抗体相关性小血管炎患者多系统临床表现和肾脏病理分析

目的 分析426例抗中性粒细胞胞浆抗体（ANCA）相关性小血管炎患者多系统的临床和病理表现。方法 回顾性分析我院1997年-2004年6月检测并明确诊断的426例ANCA相关性小血管炎患者的临床病理资料。结果 426例患者中,70例胞浆型ANCA（cANCA）阳性,均识别蛋白酶3（PR3）;354例环核型ANCA（pANCA）阳性,均识别髓过氧化物酶（MPO）。201例（47．2％,201／426）患者是在发病后3个月内确诊。临床表现呈多器官受累,其中cANCA阳性者皮疹、关节痛、眼、鼻受累的发生率显著高于pANCA阳性者,而pANCA阳性者。肾脏受累和乏力的发生率显著高于cANCA阳性者。多数患者有贫血,血沉增快,C反应蛋白增高。采用糖皮质激素联合环磷酰胺进行强化免疫抑制治疗,诱导缓解期的缓解率为88．5％。结论 ANCA相关性小血管炎在我国并非少见,临床表现呈多器官受累,ANCA检测有助于早期诊断。     

抗中性粒细胞胞质抗体的检出率及其靶抗原研究

目的　了解抗中性粒细胞胞质抗体 (ANCA)阳性检出率、流行病学特点及其靶抗原。方法　应用间接免疫荧光法 (IIF)、抗髓过氧化物酶 (MPO)和抗蛋白酶 3(PR3)酶联免疫吸附试验(ELISA)对近年送检的怀疑小血管炎的 5 6 0 4例患者血清进行了检测 ,对IIF ANCA阳性而抗MPO和抗PR3抗体均阴性的血清还进行了其他 5种ANCA特异性靶抗原的检测。并初步对ANCA阳性患者流行病学特点进行分析。结果　IIF ANCA检出率为 5 3% ,阳性检出最多在 7、8及 12月份。另外所有血清中有 390例 (7% )ANA阳性。所有血清进行抗MPO和抗PR3 ELISA检测 ,抗MPO抗体阳性 2 13例 ,抗PR3抗体阳性 32例 ,两者同时阳性 5例。 4 8例不识别MPO和PR3而IIF法阳性的血清中 13例识别其他已知靶抗原 ,识别杀菌 /通透性增高蛋白 (BPI)、人弹力蛋白酶 (HLE)、组蛋白酶G (CG)、天青杀素 (AZU)和乳铁蛋白 (LF)等靶抗原的血清分别为 7、5、1、1、0例 ,其中 1例为抗BPI和抗HLE ANCA同时阳性。 85 %的IIF ANCA阳性患者确诊为ANCA相关小血管炎。这些患者中 ,抗MPO和抗PR3的比例约为 7∶1:男女比例为 1∶1 12 ,年龄 7～ 79岁 ,平均 5 3 1岁 ,>6 0岁的老年人男女比例为 1 17∶1,而年龄 <2 0岁患者男女比例为 1∶4。结论　ANCA相关疾病在我国并不少见 ,以IIF法检     

肺脏受累的原发性抗中性粒细胞胞浆抗体相关性小血管炎43例临床分析

目的 探讨肺脏受累的原发性抗中性粒细胞胞浆抗体（ANCA）相关性小血管炎患者的临床特征,为肺部受累的原发性ANCA相关性小血管炎的诊断提供帮助.方法 回顾性分析2009年3月至2013年9月在湘雅二医院住院的符合2012年美国Chapel Hill会议关于系统性小血管炎诊断标准,并血清ANCA阳性的43例肺脏受累的的原发性ANCA相关性小血管炎患者的临床资料.结果 43例患者中,肺部症状首发就诊者22例,常见肺部症状依次为咳嗽咯痰、活动后气促、咯血、哮喘等,肺外受累器官依次为肾脏、神经系统、眼、鼻;肺外症状首发就诊者21例,肾脏为最常见受累器官;显微镜下多血管炎（MPA） 34例,其中抗髓过氧化物酶（MPO）抗体（P-ANCA）阳性率97.1％（33/34）,抗蛋白酶3（PR3）抗体（C-ANCA）阳性率2.9％ （1/34）;肉芽肿性多血管炎（GPA）（韦格纳肉芽肿）8例,抗蛋白酶3（PR3）抗体（C-ANCA）阳性率62.5％（5/8）,抗髓过氧化物酶（MPO）抗体（P-ANCA）阳性率为37.5％（3/8）;嗜酸细胞性肉芽肿性多血管炎（EGPA）1例,为抗髓过氧化物酶（MPO）抗体阳性;胸部影像学表现多为双肺间质病变,如双肺网格样改变、磨玻璃影、蜂窝肺、多发条索状及结节性病变等,或为条索或斑片状病变、支气管扩张、胸腔积液及肿块病变等.经激素和免疫抑制剂治疗多数患者病情可缓解,19例患者（44.2％）于住院及随访期间因血管炎活动并肺部感染、大咯血及肾功能衰竭等原因死亡.结论 肺脏受累的原发性ANCA相关性小血管炎临床表现无特异性,多数患者合并有肾脏受累,影像学多为肺间质病变,具有提示诊断价值,血清ANCA检查有特殊诊断价值,此类患者死亡率高,多为疾病活动并感染致死,应积极控制感染并合理采用抑制免疫治疗.     

丙基硫氧嘧啶导致的抗中性粒细胞胞质抗体阳性小血管炎及其靶抗原研究

目的 研究丙基硫氧嘧啶（PTU）引起的抗中性粒细胞胞质抗体（ANCA）阳性小血管炎的临床病理表现及其靶抗原。方法 对我院近年诊治的4例PTU引起的ANCA阳性小血管炎患者进行临床病理分析。以纯化的7种已知的ANCA靶抗原蛋白酶3（PR3）、髓过氧化物酶（MPO）、人白细胞弹力蛋白酶（HLE）、乳铁蛋白（LF）、组蛋白酶G（CG）、杀菌／通透性增高蛋白（BPI）和天青杀素（AZU）为固相抗原,采用ELISA法检测患者血清的靶抗原及治疗前后抗体滴度的变化。结果 4例病人中男女各2例,平均年龄30（11－57）岁,服PTU时间7－60个月。4例均有肾脏、肺脏、皮肤、关节肌肉和血液系统等受累,均为p-ANCA阳性,患者血清均识别MPO、LF和CG;3例识别HLE、AZU,2例识别PR3;无1例识别BPI。多数抗体滴度高,可大于1：25600;而服PTU无小血管炎临床表现的甲状腺功能亢进（甲亢）病人的30份血清均为阴性。肾活检2例为新月体性肾炎,2例为轻微病变,免疫荧光检查均为阴性。4例患者均立即停用PTU,3例应用免疫抑制剂,1例行血浆置换。4例小血管炎的临床症状均得以缓解,但1例晚期新月体肾炎患者发展为慢性肾衰竭而依赖透析。停药和治疗后各种抗体滴度均有所下降,但多未能短期阴转。结论 PTU可引起ANCA阳性小血管炎,其自身抗体可识别中性粒细胞胞质中多种已知的靶抗原;及时诊治,预后较好。     

咳嗽及肺部游走性阴影为主要表现的抗中性粒细胞胞浆抗体相关性血管炎1例

笔者成功诊治1例65岁男性抗中性粒细胞胞浆抗体（ANCA）相关性血管炎患者。该患者主要表现为慢性咳嗽和肺部游走性阴影,曾被诊断为淋巴细胞性间质性肺炎,激素治疗有效,病情复发后查MPO—ANCA阳性,结合肺穿刺活检明确诊断为ANCA相关性血管炎,加用糖皮质激素和环磷酰胺后病情再次缓解。根据文献报道和笔者的临床经验,ANCA相关性血管炎临床表现复杂,缺乏特异性,常被误诊。呼吸科医师对ANCA相关性血管炎肺部受累特点应熟悉,要重视血清ANCA的筛查,以便于本病的早期诊断。     

丙基硫氧嘧啶致ANCA阳性相关小血管炎7例临床分析

丙基硫氧嘧啶（PTU）是硫脲类抗甲状腺药,为临床最常用的抗甲状腺药物之一.抗中性粒细胞胞质抗体（ANCA）是一种以中性粒细胞和单核细胞为靶抗原的自身抗体,是可用于小血管炎检测的特异性血清学诊断标记.我院近8年发现7例PTU所致的ANCA阳性小血管炎报道如下：     

抗髓过氧化物酶抗体相关肾炎的研究进展

抗髓过氧化物酶抗体（myeloperoxidase—antineutrophil cytoplasmic antiboay，MPO—ANCA）相关肾炎是最近提出的新概念，患者血清中有抗中性粒细胞胞质α颗粒内髓过氧化物酶（myeloperoxidase，MPO）的自身抗体MPO—ANCA，病理表现为肾毛细血管及细小血管坏死或肉芽肿性血管炎造成的急进性肾小球肾炎（rapidly progressive glomerulonephfitis，RPGN），临床有血尿、慢性肾炎、慢性肾功能不全。特别是在中老年人有感染症状、贫血、全身倦怠等前驱症状后．再出现RPGN时，首先应该考虑本病。本文就MPO—ANCA相关肾炎的发病机制、临床表现、诊断、治疗及最新进展做一综述。     

抗内皮细胞抗体检测对老年ANCA相关性小血管炎病情活动程度的影响

目的探讨抗内皮细胞抗体(AECA)检测对老年抗中性粒细胞胞质抗体(ANCA)相关性小血管炎病情活动程度的预测价值。方法选取56例老年抗中性粒细胞胞浆抗体相关性小血管炎(AASV)患者作为观察组,60例健康献血者作为对照组,全部研究对象采集固定的人脐静脉内皮细胞(HUVEC)为抗原,细胞酶联免疫吸附试验(ELISA)法检测血清AECA,比较两组患者AECA阳性率的差异,分析AASV患者AECA与临床病情活动性指标的相关性。结果观察组血清AECA阳性率明显高于对照组(P0.05),不同类型AASV患者中的血清AECA阳性率比较发现,变应性肉芽肿性血管炎血清AECA阳性率明显高于显微镜下多血管炎和肉芽肿性多血管炎,肉芽肿性多血管炎血清AECA阳性率明显高于显微镜下多血管炎(P0.05),AASV病情活动期血清AECA阳性率、血清AECA和血沉(ESR)水平均明显高于病情缓解期(P0.05),且AECA阳性组BVAS分值和ESR水平明显高于AECA阴性组患者(P0.05)。结论抗内皮细胞抗体在AASV诊断和鉴别诊断、病情活动程度预测中具有重要的价值。     

Anti-myeloperoxidase antibodies in patients with rheumatoid arthritis: prevalence, clinical correlates, and IgG subclass.

OBJECTIVES--To determine the prevalence and clinical associations of autoantibodies to myeloperoxidase (MPO) in an unselected series of well-characterised outpatients with rheumatoid arthritis (RA) and to compare the distribution of IgG subclasses of anti-MPO antibodies in these patients with that in patients with systemic vasculitis. PATIENTS AND METHODS--A study was made of 97 patients with RA, who have been seen regularly in this department for up to 20 years, and 29 patients with anti-neutrophil cytoplasmic antibody (ANCA) positive systemic vasculitis. Anti-MPO antibodies were detected using a direct-binding enzyme-linked immunosorbent assay (ELISA) with MPO from human granulocytes as antigen. The IgG subclass of anti-MPO antibodies was determined by ELISA using isotype specific monoclonal antibodies. RESULTS--Anti-MPO antibodies were detected in 12% of patients with RA. Six sera contained IgG anti-MPO antibodies only, 1 IgM only and 5 antibodies of both classes. In the patients with RA the predominant subclasses were IgG1 and IgG3: only 2 sera contained detectable IgG4 antibodies. This was in contrast to patients with vasculitis, in whom most sera contained IgG1, IgG3 and IgG4 anti-MPO antibodies. Anti-MPO antibodies in sera from both patient groups bound only to the native protein. None of the patients studied with RA had evidence of vasculitis affecting the nerves or kidney: three patients (1 positive for anti-MPO antibodies and 2 negative) had cutaneous vasculitis. In the patients with RA, positivity for anti-MPO antibodies was associated with nodules and number of active joints. Three patients with anti-MPO antibodies, and none without, had pulmonary fibrosis. CONCLUSIONS--Twelve per cent of a group of unselected outpatients with RA, but without evidence of major systemic vasculitis, had anti-MPO antibodies in their serum. Positivity for anti-MPO antibodies was more common in patients with nodular disease and lung involvement but not in patients with cutaneous vasculitis. IgG4 sub-class anti-MPO antibodies were present in 90% of sera from patients with ANCA-positive vasculitis and only 2/11 (18%) of anti-MPO antibody containing sera from patients with RA.     

Follow-up of avidity and titre of anti-myeloperoxidase antibodies in sera from patients with propylthiouracil-induced vasculitis

OBJECTIVE: Propylthiouracil (PTU) has been known to induce myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positive vasculitis. Our previous study indicated that the increase of avidity of MPO-ANCA might be associated with the occurrence of clinical vasculitis in patients with PTU-induced ANCA. The current study aimed to follow-up the avidity and titre of anti-MPO antibodies in sequential sera from patients with PTU-induced ANCA-associated systemic vasculitis (AASV). METHODS: Six patients with PTU-induced vasculitis were enrolled in the current study. Serial sera in both active phase and in remission were collected. MPO-ANCA avidity was assessed by antigen-inhibition enzyme-linked immunosorbent assays (ELISAs), and avidity constant (aK) was determined as the reciprocal value of the MPO molar concentration in the liquid phase resulting in 50% inhibition of anti-MPO antibody binding to MPO in solid phase ELISA. Titres of MPO-ANCA were determined by using serial serum dilutions in MPO-ELISA. RESULTS: After cessation of PTU and initiation of immunosuppressive therapy, the avidity and titre of MPO-ANCA decreased significantly during follow-up in sera from all the patients, and the avidity decreased much more quickly than the titres. CONCLUSION: Our study indicates that avidity of anti-MPO antibodies might be more closely associated with clinical vasculitis than titre.     

In vitro up-regulation of E-selectin and induction of interleukin-6 in endothelial cells by autoantibodies in Wegener's granulomatosis and microscopic polyangiitis.

OBJECTIVE: In patients with Wegener's granulomatosis (WG) or microscopic polyangiitis (MPA) autoantibodies to myeloid granule proteins (ANCA), particularly proteinase 3 (Pr3) and myeloperoxidase (MPO), and to endothelial cells (AECA) are frequently detected. The role of these autoantibodies in the development of vascular injury is incompletely understood. Since the expression of E-selectin and the production of interleukin 6 by endothelial cells is an early step in the sequence of events leading to vascular injury, we examined the capacity of IgG fractions from patients with WG and/or MPA to activate endothelial cells to the expression of E-selectin and the production of IL-6. We related those findings to the presence of ANCA and AECA in the IgG preparations. METHODS: Human umbilical vein endothelial cells (HUVEC) were incubated with immunoglobulin (IgG) preparations from 28 patients (17 positive for anti-Pr3, 10 for anti-MPO, and one for anti-Pr3/MPO) with active vasculitis and from 10 healthy volunteers. The final IgG concentration in the activation assay was 2 mg/ml. TNF alpha (10 ng/ml) and LPS (10 ng/ml) were used as positive controls for HUVEC activation. The extent of HUVEC activation was assessed by the measurement of E-selectin expression by flow cytometry (after 4 hours of incubation) and the production of interleukin 6 by ELISA (after 24 hours). RESULTS: We found that 11 of the 28 ANCA positive IgG samples were capable of activating endothelial cells: six samples induced IL-6 production alone, one sample upregulated E-selectin expression alone, and four samples induced both IL-6 production and E-selectin upregulation. Five of 17 anti-Pr3 positive samples (one of which was also positive for AECA) and 6 of 10 anti-MPO positive samples (all simultaneously positive for AECA) induced endothelial cell activation. AECA positive samples that induced endothelial cell activation (n = 7) had higher AECA titres than samples that did not induce endothelial cell activation (n = 6). CONCLUSION: Our data suggest that the activation of endothelial cells in patients with WG and MPA can be induced by circulating autoantibodies. Both ANCA and AECA can be responsible for this effect.     

Predominance of IgG1 and IgG3 subclasses of autoantibodies to neutrophil cytoplasmic antigens in patients with systemic lupus erythematosus

The IgG subclasses displayed by antibodies to four neutrophil cytoplasmic antigens were studied in 20 patients with systemic lupus erythematosus (SLE) by solid-phase enzyme immunoassays and monoclonal antibodies to human IgG subclasses. The IgG subclass reactivity of antineutrophil cytoplasmic antibodies (ANCA) was measured in six sera containing antiproteinase3 (PR3) antibodies, in five sera containing antimyeloperoxidase (MPO) antibodies, in sera containing antibactericidal/permeability-increasing protein (BPI) antibodies, and in ten sera containing antilactoferrin (LF) antibodies. The IgG subclass distribution of anti-dsDNA antibodies in eight sera was examined as well. IgGI was the predominant subclass for MPO-ANCA and LF-ANCA, whereas IgG1/IgG3 contributed mainly to anti-PR3, anti-BPI antibodies, and anti-dsDNA antibodies. In addition, we found elevated levels of the total IgG1 and IgG3 isotypes in the sera of our patients. Our results demonstrated a predominance of IgG1/IgG3 ANCA in SLE, suggesting that the isotype distribution of ANCA is a feature of antibody production in this disease.     

IgA nephropathy with crescentic glomerulonephritis and ANCA positive

We present a case of IgA nephropathy diagnosed by renal biopsy that presents after 2 years of folow-up an impairment of the renal function associate histoligically to a crescentic glomerulonephritis. The immunologic determinations showed of high titers of antineutrophil cytoplamic antibodies (ANCA) (P-ANCA IgG antiMPO and P-ANCA IgA anti-MPO). The patient began treatment with haemodyalisis and one year later she received a cadaveric kidney transplantation with good result. Two years later she had normal urine sediment, negative proteinuria, normal renal function but high titers of IgG and IgA PANCA anti-MPO. In summary, we believe that the determination ANCA in acute renal failure due to IgA nephropathy can indicate the existence of a IgA crescentic glomerulonephritis superimposed or an associated small vessel vasculitis and it confers a worse prognosis. The positive maintenance of IgG P-ANCA anti-MPO IgG anti-MPO titers during the course suggests that the sequential determination of ANCA in this entity is not useful to the monitoring of the clinical activity.     

Evaluation of antineutrophil cytoplasmic antibody seroconversion induced by minocycline, sulfasalazine, or penicillamine

OBJECTIVE: Case reports have suggested that minocycline, sulfasalazine, and penicillamine are associated with antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. This study evaluated ANCA seroconversion due to these agents in serum samples prospectively collected in randomized, double-blind, controlled trials. METHODS: The sources of study sera were 3 clinical trials: 1) a 48-week trial of minocycline for early rheumatoid arthritis, with 64 patients receiving minocycline compared with 68 receiving placebo; 2) a 37-week trial of sulfasalazine for rheumatoid arthritis, with 51 receiving sulfasalazine compared with 38 receiving placebo; and 3) a 104-week trial of penicillamine for early systemic sclerosis, with 15 undergoing high-dose penicillamine treatment versus 12 receiving low-dose penicillamine. ANCA were measured in the baseline and study-end serum samples by indirect immunofluorescence (IIF) for perinuclear ANCA (pANCA) and cytoplasmic ANCA (cANCA) patterns, and by antigen-specific enzyme-linked immunosorbent assay (ELISA) for antibodies to myeloperoxidase (anti-MPO) and proteinase 3 (anti-PR3). Laboratory personnel were blinded to the group identity of the samples. ANCA results were interpreted using an ANCA scoring system that combines the results of IIF and ELISA testing. RESULTS: No patient in any of the active study drug groups demonstrated ANCA seroconversion according to the final interpretation of the combined IIF and ELISA results. Twelve of the 248 patients (5%) were positive for anti-MPO with pANCA at baseline. No subject was positive for anti-PR3 with cANCA. There were no findings suggestive of vasculitis in any of these patients. CONCLUSION: From our study results, there was no suggestion of ANCA seroconversion induced by minocycline, sulfasalazine, or penicillamine. However, these findings do not rule out the possibility of rare, sporadic cases of either ANCA seroconversion or true drug-induced vasculitis with these drugs.     

Diagnostic performance of antineutrophil cytoplasmic antibody tests for idiopathic vasculitides: metaanalysis with a focus on antimyeloperoxidase antibodies

OBJECTIVE: The diagnostic value of tests for antimyeloperoxidase antibodies (anti-MPO) for systemic vasculitis is less established than that for cytoplasmic antineutrophil cytoplasmic antibody (cANCA)/antiproteinase 3 antibodies (anti-PR3). Controversy exists regarding the optimal utilization of indirect immunofluorescence (IIF) ANCA testing versus antigen-specific ANCA testing. To summarize the pertinent data, we conducted a metaanalysis examining the diagnostic value of ANCA testing systems that include assays for anti-MPO. METHODS: We performed a structured Medline search and reference list review. Target articles in the search strategy were those reporting the diagnostic value of immunoassays for anti-MPO for the spectrum of systemic necrotizing vasculitides that includes Wegener's granulomatosis, microscopic polyangiitis, the Churg-Strauss syndrome, and isolated pauci-immune necrotizing or crescentic glomerulonephritis, regardless of other types of ANCA tests. Inclusion criteria required specification of a consecutive or random patient selection method and the use of acceptable criteria for the diagnosis of vasculitis exclusive of ANCA test results. Weighted pooled summary estimates of sensitivity and specificity were calculated for anti-MPO alone, anti-MPO + perinuclear ANCA (pANCA), and anti-MPO/pANCA + anti-PR3/cANCA. RESULTS: Of 457 articles reviewed, only 7 met the selection criteria. Summary estimates of sensitivity and specificity (against disease controls only) of assays for anti-MPO for the diagnosis of systemic necrotizing vasculitides were 37.1% (confidence interval 26.6% to 47.6%) and 96.3% (CI 94.1% to 98.5%), respectively. When the pANCA pattern by IIF was combined with anti-MPO testing, the specificity improved to 99.4%, with a lower sensitivity, 31.5%. The combined ANCA testing system (anti-PR3/cANCA + anti-MPO/pANCA) increased the sensitivity to 85.5% with a specificity of 98.6%. CONCLUSION: These results suggest that while anti-MPO is relatively specific for the diagnosis of systemic vasculitis, the combination system of immunoassays for anti-MPO and IIF for pANCA is highly specific and both tests should be used together given the high diagnostic precision required for these conditions. Because patients with ANCA associated vasculitis have either anti-MPO with pANCA or anti-PR3 with cANCA, and rarely both, a combined ANCA testing system including anti-PR3/cANCA and anti-MPO/pANCA is recommended to optimize the diagnostic performance of ANCA testing.     

Immunoglobulin G subclasses of antibodies to hepatitis B core antigen in HBs antigen positive liver diseases

Serum immunoglobulin G (IgG) subclasses of hepatitis B core antibody (anti-HBc) in 54 patients with different types of hepatitis B surface antigen positive (HBsAg+) liver diseases (asymptomatic carrier (ASC), acute hepatitis (AH), chronic hepatitis (CH) and liver cirrhosis (LC)) and 18 normal controls were estimated by enzyme-linked immunosorbent assay (ELISA) using subclass specific anti-human mouse monoclonal antibodies. In 11 cases, the estimations were carried out at both exacerbation and remission stages of chronic active hepatitis (CAH). In 4 cases of CAH, serial observations of anti-HBc IgG subclasses were made according to the clinical course. In 5 cases of CAH, the estimations were carried out at the HBe antigen positive (HBeAg+) stage and after sero-conversion to anti-HBe positive (anti-HBe+) stage. In ASC the main anti-HBc IgG subclasses were restricted to one subclass--anti-HBc IgG1. In AH on the other hand, all the subclasses were represented. In CH all the subclasses were detected under different diagnostic conditions but anti-HBc IgG1 was the main subclass. In LC the mean concentration of anti-HBc IgG3 was higher than the concentration of anti-HBc IgG1. In exacerbation stages of CAH, the different anti-HBc IgG subclasses had higher concentrations than in remission stages. The concentrations of different anti-HBc IgG subclasses fell just after seroconversion from HBeAg+ stage to anti-HBe+ stage. These data suggest that the estimation of anti-HBc IgG subclasses may be helpful in establishing the diagnosis of different types and stages of HBsAg+ liver diseases.     

The effect of anti-tuberculosis treatment on levels of anti-phospholipid and anti-neutrophil cytoplasmatic antibodies in patients with active tuberculosis

The aim of this study is to determine the prevalence and effect of anti-tuberculosis treatment on anti-phospholipid antibodies and anti-neutrophil cytoplasmatic antibodies (ANCA) in patients with active mycobacterial infections. Thirty-three consecutive patients (age 56 years, 26 males) with recently diagnosed active tuberculosis (TB) were enrolled. Data included clinical disease features, symptom duration, multidrug resistance and presence of HIV. Serum samples taken before and after TB treatment were frozen at ?20 °C and tested for anti-cardiolipin IgG (aCL), anti–β2 glycoprotein IgG (anti-β2GPI), anti-prothrombin, anti-proteinase 3 (PR3), myeloperoxidase (MPO), bactericidal/permeability (BPI) and lactoferrin. Thirty percent of patients had higher than cut-off value for anti-β2GPI, and 9 % had increased aCL. The levels of antibodies against β2GPI and aCL normalized post-treatment. A substantial proportion of patients had high baseline anti-PR3, MPO, BPI and lactoferrin levels. Most anti-lactoferrin and anti-MPO levels decreased post-treatment, while anti-PR3 increased in most of the baseline-positive patients. Some patients had de novo anti-PR3 and MPO formation after 6-month treatment. Patients with active TB have significantly increased anti-β2GPI and ANCA titers. While anti-β2GPI titers normalize post-treatment, ANCA behave in a complex way. Anti-TB treatment may induce normalization of anti-lactoferrin and anti-MPO, and de novo anti-PR3 and MPO formation.     

IgG subclass serum levels in juvenile chronic arthritis.

IgG subclass levels of sera from 26 patients with juvenile chronic arthritis (JCA) were determined by means of mouse monoclonal antibodies. Patients were divided into three groups according to clinical activity of the disease: active disease, partial remission, and remission. One hundred and sixty four age matched, healthy children served as controls. IgG subclass concentrations were log transformed, and a robust regression method was applied to obtain expected values for the different ages. We found a significant increase of IgG3 (p less than 0.0001), IgG1 (p less than 0.002), and IgG2 (p less than 0.035) in JCA sera, while IgG4 values did not differ significantly from those of controls. When patients were divided according to clinical activity significant increases of IgG2 and IgG4 were observed in the patients in partial remission. Our data suggest that differential increase of IgG subclasses during the courses of JCA may be of relevance to the pathogenesis of the disease.