Clinical Predictors of Outcome in Patients with Anti-neutrophil Cytoplasmic Autoantibody-related Renal Vasculitis： Experiences from a Single-center

Background： Primary anti-neutrophil cytoplasmic antibody-associated vasculitis （AAV） is a chronic autoimmune disease associated with multisystem dysfunction. Renal involvement is common and closely associated with outcome. The purpose of this study was to investigate the clinical determinants of mortality of patients with AAV-related renal injury in the first 2 years after diagnosis in a single West Chinese center. Methods： Demographic and laboratory parameters of 123 consecutive patients with AAV-related renal injury diagnosed in Renal Division and Institute ofNephrology, Sichuan Provincial People＇s Hospital between 2004 and 2012 were collected retrospectively. All patients were followed up for 2 years after diagnosis. Survivors were compared with nonsurvivors to identify the clinical baseline variables associated with mortality. Multivariate Cox regression model was used to determine the independent predictors of mortality. Results： Of the 123 patients, 46 （37.4%） died by the end of 2 years after diagnosis, with 41 （33.3%） patients dying within the first 12 months. In comparison with the survivors, Birmingham Vasculitis Activity Score （BVAS）, the incidence of pulmonary hemorrhage and digestive system （DS） involvement, serum creatinine, and erythrocyte sedimentation rate were significantly higher in nonsurvivors, whereas lymphocyte counts, hemoglobin, and complement 3 （C3） were significantly lower. Renal replacement therapy was more common in nonsurvivors. High BVAS （hazard ratio [HR] = 1.058, 95% confidence interval [CI]： 1.002-1. I17; P = 0.042）, pulmonary hemorrhage （MR = 1.970, 95% CI： 1.033-3.757; P = 0.04）, DS involvement （HR = 2.911,95% （7：1.212-6.911 ： P = 0.017）4 and serum creatinine 〉400 μmol/L （MR = 2.910, 95% CI： 1.271-6.664, P = 0.012） were independent predictors of death in patients with AAV-related renal injury. Conclusions： Patients with AAV-related renal injury have high early mortality. Those with high BVAS （particularly with pulmonary or DS involvement） and serious renal dysfunction should receive aggressive therapy and careful monitoring to reduce the occurrence of adverse events and improve prognosis.

Dynamically changing antineutrophil cytoplasmic antibodies in granulomatosis with polyangiitis:A case report

BACKGROUND Granulomatosis with polyangiitis(GPA)is one of the most prevalent forms of the antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis.GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis.The diagnosis of GPA depends on clinical presentation,serological evidence of a positive ANCA,and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation.Cytoplasmic ANCA(c-ANCA)is positive in 65%-75% of GPA patients,accompanied by proteinase 3(PR3),the main target antigen of c-ANCA,another 5% of GPA patients had negative ANCA.CASE SUMMARY The patient,a 52-year-old male,presented with unexplained nasal congestion,tinnitus,and hearing loss.After a duration of 4 months experiencing these symptoms,the patient subsequently developed fever and headache.The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis,and the ANCA results were negative.The anti-infective therapy proved to be ineffective,but the patient's symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day.However,after continuous use of methylprednisolone tablets for 3 months,the patient experienced a recurrence of fever accompanied by right-sided migraine,positive c-ANCA and PR3,and increased total protein in cerebrospinal fluid.The and cyclophosphamide 0.8 g monthly,the patient experienced alleviation of fever and headache.Additionally,the ANCA levels became negative and there has been no recurrence.CONCLUSION For GPA patients with negative ANCA,there is a potential for early missed diagnosis.The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA.

Perinuclear anti-neutrophil cytoplasmic antibodies (p-anca) in chronic ulcerative colitis: Experience in a Mexican institution

AIM： To assess the prevalence and clinical value of p-ANCA in a sample of Mexican ulcerative colitis （UC） patients. METHODS： In a prospective, IRB-approved protocol, p-ANCA was determined in 80 patients with UC （mean age, 32 ± 12.9 years）. The severity and extension of disease were determined by clinical methods, searching a statistical association with p-ANCA status. RESULTS： p-ANCA were detected in 41 （51%） patients. Severity of disease was the only clinical variable statistically associated with their presence （P 〈 0.0001; OR = 9; CI 95% = 3.2-24.7）. CONCLUSION： The prevalence of p-ANCA was similar to that reported in other countries. Their presence was associated to UC severity, but offered no more information than the obtained by clinical methods.

Differentiation of Behcet's disease from inflammatory bowel diseases:Anti-saccharomyces cerevisiae antibody and anti-neutrophilic cytoplasmic antibody

The differential diagnosis of Behcet's disease(BD) from inflammatory bowel disease(IBD) is sometimes difficult and challenging.Hereby,we suggested the utility of anti-saccharomyces cerevisiae antibody(ASCA) and anti-neutrophilic cytoplasmic antibody(p-ANCA) in the differential diagnosis of BD from IBD.

Anti-Neutrophil Cytoplasmic Antibody Vasculitis in Pediatric Patients: Is the Incidence Rising?

Objectives: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disease usually seen in middle-aged and older adults but which is rare in children and adolescents. We sought to determine if there has been a change in the incidence of this disorder. Methods: Single-center, retrospective review. Results: Over the last 2 years, we have encountered a striking increase in the frequency of this disease in pediatric patients. All eight patients seen during this period had renal involvement and 5 patients rapidly progressed to end stage kidney disease. The prognosis was worse in younger patients, those with microscopic polyangiitis, and those with chronic kidney damage in the diagnostic renal biopsy. Conclusions: We report these observations to highlight this change in the epidemiology of ANCA-associated vasculitis and to promote earlier recognition and treatment of this severe form of glomerulonephritis.

Autoimmune liver disease-related autoantibodies in patients with biliary atresia

AIM To investigate the prevalence and clinical significance of autoimmune liver disease(ALD)-related autoantibodies in patients with biliary atresia(BA).METHODS Sera of 124 BA patients and 140 age-matched non-BA controls were assayed for detection of the following autoantibodies: ALD profile and specific anti-nuclear antibodies(ANAs), by line-blot assay; ANA and antineutrophil cytoplasmic antibody(ANCA), by indirect immunofluorescence assay; specific ANCAs and antiM2-3 E, by enzyme linked immunosorbent assay. Associations of these autoantibodies with the clinical features of BA(i.e., cytomegalovirus infection, degree of liver fibrosis, and short-term prognosis of Kasai procedure) were evaluated by Spearman's correlation coefficient.RESULTS The overall positive rate of serum autoantibodies in preoperative BA patients was 56.5%. ALD profile assay showed that the positive reaction to primary biliary cholangitis-related autoantibodies in BA patients was higher than that to autoimmune hepatitis-related autoantibodies. Among these autoantibodies, anti-BPO was detected more frequently in the BA patients than in the controls(14.8% vs 2.2%, P < 0.05). Accordingly, 32(25.8%) of the 124 BA patients also showed a high positive reaction for anti-M2-3 E. By comparison, the controls had a remarkably lower frequency of anti-M2-3 E(P < 0.05), with 6/92(8.6%) of patients with other liver diseases and 2/48(4.2%) of healthy controls. The prevalence of ANA in BA patients was 11.3%, which was higher than that in disease controls(3.3%, P < 0.05), but the reactivity to specific ANAs was only 8.2%. The prevalence of ANCAs(ANCA or specific ANCAs) in BA patients was also remarkably higher than that in the healthy controls(37.9% vs 6.3%, P < 0.05), but showed no difference from that in patients with other cholestasis. ANCA positivity was closely associated with the occurrence of postoperative cholangitis(r = 0.61, P < 0.05), whereas none of the autoantibodies showed a correlation to cytomegalovirus infection or the stages of liver fibrosis.CONCLUSION High prevalence of autoantibodies in the BA developmental process strongly reveals the autoimmunemediated pathogenesis. Serological ANCA positivity may be a useful predictive biomarker of postoperative cholangitis.

Update on Anti-Saccharomyces cerevisiae antibodies, anti-nuclear associated anti-neutrophil antibodies and antibodies to exocrine pancreas detected by indirect immunofluorescence as biomarkers in chronic inflammatory bowel diseases: Results of a multicent

AIM： Anti-Saccharomyces anti-nuclear associated cerevisiae antibodies （ASCA）, anti-neutrophil antibodies （NANA） and antibodies to exocrine pancreas （PAB）, are serological tools for discriminating Crohn＇s disease （CrD） and ulcerative colitis （UC）. Like CrD, coeliac disease （COD） is an inflammatory bowel disease （IBD） associated with （auto） antibodies. Performing a multicenter study we primarily aimed to determine the performance of ASCA, NANA and PAB tests for IBD diagnosis in children and adults, and secondarily to evaluate the prevalence of these markers in CoD. METHODS： Sera of 109 patients with CrD, 78 with UC, 45 with CoD and 50 healthy blood donors were retrospectively included. ASCA, NANA and PAB were detected by indirect immunofluorescence （IIF）. RESULTS： ASCA＋/NANA- profile displayed a positive predictive value of 94.2% for CrD. Detection of ASCA was correlated with a more severe clinical profile of CrD and treatment of the disease did not influence their serum levels. ASCA positivity was found in 37.9% of active CoD.PAB were found in 36.7% CrD and 13.3% CoD patients and were not correlated with clinical features of CrD, except with an early onset of the disease. Fifteen CrD patients were ASCA negative and PAB positive. CONCLUSION： ASCA and PAB detected by IIF are specific markers for CrD although their presence does not rule out a possible active CoD. The combination of ASCA, NANA and PAB tests improves the sensitivity of immunological markers for CrD. Repeating ASCA, NANA, and PAB testing during the course of CrD has no clinical value.

CLINICAL AND PATHOLOGICAL MANIFESTATI-ONS OF PATIENTS WITH ANTINEUTROPHIL CYTO-PLASMIC AUTOANTIBODIES DIRECTED AGA INST PROTEINASE 3 OR MYELOPEROXIDASE

To compare the clinical and pathological manifestations of patients with antineutrophil cytoplasmic autoantibodies (ANCA) directed against proteinas e 3 (anti PR3) or myeloperoxidase (anti MPO). Methods. One hundred and forty patients with ANCA were detected for anti PR3 a nd anti MPO by ELISA. The clinical features at presentation, histopathological characteristics and outcome of all patients who were tested positive for anti P R3 or anti MPO were analysed.Results. In anti PR3 group (n=21), 16 cases (76.2%) had systemic vasculitis , in which Wegener’s granulomatosis prevailed (13 cases, 61.9%). In anti MPO g roup (n=31), 19 cases (61.3%) were diagnosed as systemic vasculitis and 12 case s (38.7%) as microscopic angiitis. For vasculitic patients with anti PR3 and a nti MPO, the disease duration at diagnosis was 9.6±2.0m and 4.4±0.9m respecti vely, P< 0.05;vasculitis activity index (BVAS) and mean number of affected organ were 22.5±2.1, 5.0±0.4 and 25.1±1.7, 4.8±0.4 respectively, P >0.05;upper r espiratory tract, eye and joint involvements were 11(68.8%), 7(43.8%), 11(68.8 %) and 7(36.8%), 2(10.5%), 5(26.3%) respectively, P< 0.05.Although there was no statistical difference in renal involvement between these two groups, patien ts with serum creatine >500 μmol/L were more commonly seen in anti MPO group t han in anti PR3 group, which were 8(42.1%) and 2(12.5%) respectively, P< 0.05 . Ten relapses were seen in anti PR3 group and only 2 in anti MPO group, but t he acute mortality rate in anti MPO group (5/19, 27.4%) was much higher than t hat in anti PR3 group (1/16, 6.3%). Conclusions. Anti PR3 and anti MPO occurred mainly in systemic vasculitis. A large divergence was seen in the disease spectrum between patients with anti PR 3 and those with anti MPO. In particular, upper respiratory tract, eye and join t involvements, granuloma formation and relapse were more prominent in anti PR3 patients. By contrast, the anti MPO patients had a more acute disease onset, m ore rapid progressive renal involvement and a higher acute mortality rate.

耳鼻受累首发的肉芽肿性血管炎1例

1临床资料患者,女,57岁,既往体健,因“右耳不适1个月”于2022-01-03收治入院。1个月前患者因右耳耳闷伴轻度听力下降反复就诊于当地医院,考虑分泌性中耳炎,经口服抗生素、激素等药物保守治疗后未能完全缓解,收治于我科。专科查体:右耳耳道湿润可见淡黄色脓液,稍黏稠,量稍多,鼓膜充血肿胀,标志欠清,鼓室可见积液(图1A)。

Drug-induced anti-neutrophil cytoplasmic antibody-associated vasculitis

Objective:In recent years,an increasing number of drugs have been proved to be associated with the induction of anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).This article reviews the latest research progress on drug-induced AAV.Data sources:We conducted a comprehensive and detailed search of the PubMed database.The search terms mainly included druginduced,ANCA,and vasculitis.Study selection:We summarized the original articles and reviews on drug-induced AAV in recent years.The extracted information included the definition,epidemiology,associated drugs,pathogenesis,clinical features,diagnosis,treatment,and prognosis of druginduced AAV.We also focused on the differences between drug-induced AAV and primary vasculitis.Results:The offending drugs leading to drug-induced AAV are almost from pharmacologic categories and we need to be vigilant when using these drugs.The pathogenesis of drug-induced AAV might be multifactorial.The formation of neutrophil extracellular traps is an important mechanism for the development of drug-induced AAV.The clinical features of drug-induced AAV are similar to those of primary AAV.Understanding the difference between drug-induced AAV and primary AAV is helpful to identify druginduced AAV.Stopping the offending drug at once after diagnosis may be sufficient for those patients with mild symptoms.Immunosuppressive therapy should only be used in patients with vital organs involvement.Conclusions:Patients with drug-induced AAV usually have a good prognosis if they stop using the offending drug immediately.Recent advances in research on AAV are expected to help us better understand the pathogenesis of drug-induced AAV.

Propylthiouracil induced anti-neutrophil cytoplasmic antibody-associated vasculitis with bone marrow plasmacytosis and granulocytopenia

Antithyroid drugs are molecules known as thionamides that inhibit thyroid hormone synthesis by interfering with thyroid peroxidase mediated iodination of tyrosine residues in thyroglobulin. These extensively used drugs are associated with a variety of well-known side effects such as anti-neutrophil cytoplasmic antibody （ANCA）-positive vasculitis, granulocytopenia and aplastic anemia. Recently, an atypical hematological finding -- bone marrow plasmacytosis, related to the use of methimazole -- was reported twice in English literatures, but bone marrow plasmacytosis with the use of propylthiouracil （PTU） has hardly been reported so far. Herein we present a case of a patient with Graves＇ disease who was initially investigated for plasma cell dyscrasia but finally diagnosed as PTU-induced bone marrow plasmacytosis with granulocytopenia and ANCA-associated vasculitis.

Eosinophilic granulomatosis with polyangiitis,asthma as the first symptom,and subsequent Loeffler endocarditis:A case report

BACKGROUND Eosinophilic granulomatosis with polyangiitis(EGPA),formerly known as Churg-Strauss syndrome,is a rare form of anti-neutrophil cytoplasmic antibodyassociated vasculitis characterized by asthma,vasculitis,and eosinophilia.CASE SUMMARY We report an atypical case of EGPA in a 20-year-old female patient.Unlike previously reported cases of EGPA,this patient’s initial symptom was asthma associated with a respiratory infection.This was followed by Loeffler endocarditis and cardiac insufficiency.She received treatment with methylprednisolone sodium succinate,low molecular weight heparin,recombinant human brain natriuretic peptide,furosemide,cefoperazone sodium/sulbactam sodium,and acyclovir.Despite prophylactic anticoagulation,she developed a large right ventricular thrombus.EGPA diagnosis was confirmed based on ancillary test results and specialty consultations.Subsequent treatment included mycophenolate mofetil.Her overall condition improved significantly after treatment,as evidenced by decreased peripheral blood eosinophils and cardiac markers.She was discharged after 17 d.Her most recent follow-up showed normal peripheral blood eosinophil levels,restored cardiac function,and a reduced cardiac mural thrombus size.CONCLUSION This case illustrates the swift progression of EGPA and underscores the significance of early detection and immediate intervention to ensure a favorable prognosis.

Association between follistatin-related protein 1 and the functional status of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Background:Follistatin-like 1(FSTL1)plays both pro-inflammatory and anti-inflammatory roles in the inflammatory processes.We investigated whether serum FSTL1 could predict the current anti-neutrophil cytoplasmic antibody-associated vasculitis(AAV)-specific indices.Methods:We randomly selected 74 patients with AAV from a prospective and observational cohort of Korean patients with AAV.Clinical and laboratory data and AAV-specific indices were recorded.FSTL1 concentration was determined using the stored sera.The lowest tertile of the short-form 36-item health survey(SF-36)was defined as the current low SF-36.The cutoffs of serum FSTL1 for the current low SF-36 physical component summary(PCS)and SF-36 mental component summary(MCS)were extrapolated by the receiver operator characteristic curve.Results:The median age was 62.5 years(55.4%were women).Serum FSTL1 was significantly correlated with SF-36 PCS(r=-0.374),SF-36 MCS(r=-0.377),and C-reactive protein(CRP)(r=0.307),but not with Birmingham vasculitis activity score(BVAS).In the multivariable linear regression analyses,BVAS,CRP,and serum FSTL1 were independently associated with the current SF-36 PCS(β=-0.255,β=-0.430,andβ=-0.266,respectively)and the current SF-36 MCS(β=-0.234,β=-0.229,andβ=-0.296,respectively).Patients with serum FSTL1≥779.8 pg/mL and those with serum FSTL1≥841.6 pg/mL exhibited a significantly higher risk of having the current low SF-36 PCS and SF-36 MCS than those without(relative risk 7.583 and 6.200,respectively).Conclusion:Serum FSTL1 could predict the current functional status in AAV patients.

Analysis of clinical features and prognosis of anti-glomerular basement membrane antibody positive patients with anti-neutrophil cytoplasmic antibodies

Objective To investigate the characteristics and outcome of glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody.Methods The sera of 23 antiGBM glomerulonephritis patients were collected and were tested for ANCA respectively.Characteristics and outcome of patients with coexisting anti-GBM antibody

双重血浆置换治疗抗中性粒细胞胞质抗体相关血管炎严重肾损害的临床疗效

目的:观察双重血浆置换(double filtration plasmapheresis,DFPP)治疗抗中性粒细胞胞质抗体(ANCA)相关血管炎(ANCA associated vasculitis,AAV)的初步临床疗效。方法:12例活动期AAV患者(男7例,女5例,年龄43～72岁),BVAS评分14.7±3.2分,其中10例p/MPO-ANCA阳性,2例c/PR3-ANCA阳性,ANCA水平221.3～341.4RU/ml(平均274.9±33.9RU/ml)。平均血清肌酐(SCr)549.9±197.1μmol/L,临床表现均符合急进性肾炎综合征(RPGN),均需要肾脏替代治疗。肾活检病理类型分为新月体型(细胞性新月体≥50%,5例),混合型(细胞性新月体<50%,肾小球硬化<50%,3例),局灶型(≥50%肾小球正常,1例)和硬化型(≥50%肾小球硬化,3例)。DFPP采用血浆分离器EC50W作一级滤器,血浆成分分离器EC20W作二级滤器,每次处理血浆量为2倍血浆容量。均同时给予甲泼尼松静脉治疗(0.5g/d,3～6d),后续采用激素联合吗替麦考酚酯或间断静脉环磷酰胺冲击治疗。观察DFPP治疗前后血清ANCA水平变化和对肾功能的影响。结果:DFPP治疗3～5次,治疗结束时ANCA水平显著下降[(274.9土33.9)RU/mlvs(111.8±55.1)RU/ml,P<0.01],平均下降(60.0±18.1)%。10例(83.3%)摆脱透析,1例(新月体型)仅随访1月,尚未摆脱透析,1例(硬化型)肾功能无改善,转为维持性肾脏替代治疗。摆脱透析的10例患者平均随访6.2±4.8月(1～15月),1例(局灶型)肾功能恢复正常,8例(新月体型和混合型各3例,硬化型2例)SCr稳定,1例(新月体型)1月后SCr再次升高行肾脏替代治疗。DFPP治疗过程中无明显不良反应。结论:DFPP能有效清除AAV患者血清ANCA,改善肾功能,但其疗效还需大样本临床对照试验研究的证实。

丙基硫氧嘧啶相关血管炎肾损害的临床病理特征及转归

目的:回顾性分析丙基硫氧嘧啶(PTU)相关ANCA血管炎伴肾脏损害患者临床、病理特征及转归。方法:因Graves病或自身免疫性甲状腺炎引起甲状腺功能亢进,服用PTU后出现血清ANCA阳性伴肾脏损害患者12例[女性11例,男性1例,平均年龄(32.4±13.8)岁],均行肾活检病理检查和随访。回顾性分析患者的临床病理特征和转归。结果:12例患者服用PTU2～264月(中位时间42月),肾脏病程(11.5±20.1)月,ANCA类型均为P-ANCA,其中11例为MPO-ANCA阳性,1例MPO-/PR3-ANCA双阳性。临床均表现血尿(其中5例肉眼血尿)及蛋白尿[(1.9±1.6g/24h)],7例(58.3%)存在肾功能不全[SCr(282.88±335.92)μmol/L],其中3例入院时即需要肾脏替代治疗。肾活检病理10例为寡免疫复合物节段坏死性肾炎伴新月体形成,2例为节段坏死性肾炎伴膜性病变。治疗上均停用PTU并接受免疫抑制治疗,随访3～60月(中位时间19月),1例进入终末期肾衰,1例SCr倍增,2例转为慢性肾功能不全,8例完全缓解(肾功能正常,尿检阴性)。血清ANCA2例转阴,9例滴度下降,1例无变化。3例肾血管炎复发伴血清ANCA滴度升高。结论:本组PTU相关血管炎肾功能损害严重,病理改变除与ANCA相关的肾血管炎外,还合并膜性病变,预后不佳,停用PTU后ANCA持续阳性且滴度升高与复发相关,表明对ANCA水平升高者需维持免疫抑制治疗。

5种ANCA相关性血管炎活动性评分量表的比较

目的比较5种系统性血管炎活动性评分量表的可靠性及相关性,以指导临床应用。方法以45例抗中性粒细胞胞浆抗体(anti-neutrophil cytoplasmic autoantibody,ANCA)相关性血管炎(ANCA-associated vasculitis,AAV)患者为研究对象,其中包括韦格纳肉芽肿(wegener’s granulomatosis,WG)患者30例和显微镜下多血管炎(microscopic polyangitis,MPA)患者15例。由2名评测者分别根据下述5种目前国际上常用的活动指数评价量表进行计分:伯明翰血管炎活动性评分(the Birmingham VasculitisActivity Score,BVAS1994),韦格纳肉芽肿专用的BVAS(the BVAS for Wegener granulomatosis,BVAS/WG),BVAS2003,疾病累及范围指数(the Disease Extent Index,DEI),5因子评分(the Five Factor Score,FFS)。结果5种评分量表均有很高的重复信度(ICC0.97～0.98)和评测者间信度(ICC 0.93～0.98)。BVAS1994与BVAS2003(rs=0.961)、BVAS/WG(rs=0.872)、及DEI(rs=0.818),BVAS2003与BVAS/WG(rs=0.872)、DEI(rs=0.826),BVAS/WG与DEI(rs=0.776)间有较高的相关性,P值均小于0.001。FFS与其他评分量表之间无相关性。结论目前AAV活动性评分量表是可靠、有效的。应用不同评分量表所得数据之间可以相互比较。

分子伴侣性自噬参与LAMP-2抗体诱导中性粒细胞胞外捕网形成

目的探讨分子伴侣性自噬在LAMP-2抗体诱导中性粒细胞胞外捕网(NETs)形成的作用及机制。方法采用PolymorphprepTM方法分离健康志愿者和抗中性粒细胞胞浆抗体相关性血管炎(AAV)患者外周静脉血中的中性粒细胞,直接离体或LAMP-2抗体刺激健康人外周血中性粒细胞,通过自噬阻断剂3-甲基腺嘌呤(3-MA)和放线菌酮(CHX)进行干预,免疫荧光观测NETs的形成,免疫荧光法和免疫印迹法检测分子伴侣自噬相关蛋白LAMP-2A、Hsc70的表达。结果与正常中性粒细胞组相比,AAV患者中性粒细胞LAMP-2A表达增加(P=0.002 3);LAMP-2抗体可诱导中性粒细胞LAMP-2A、Hsc70蛋白表达明显上调(P<0.01),CHX能明显降低LAMP-2抗体引起的LAMP-2A、Hsc70蛋白表达(P<0.000 1);与3-MA组相比,CHX组能明显减少LAMP-2抗体诱导的NETs形成(P<0.000 1)。结论 LAMP-2抗体可诱导人中性粒细胞分子伴侣性自噬增强及NETs形成,放线菌酮可抑制此过程,提示分子伴侣性自噬可能参与了NETs的形成。

4种自身抗体对间接免疫荧光法检测抗中性粒细胞胞质抗体的影响

目的:观察抗核抗体、抗线粒体抗体、抗高尔基体抗体和抗核糖体P蛋白抗体对间接免疫荧光(ⅡF)法检测抗中性粒细胞胞质抗体(ANCA)结果的影响。方法:用ⅡF法检测4种自身抗体阳性血清可能出现的ANCA荧光图谱;用ELISA法确认上述4种血清的靶抗原。结果:用乙醇固定的中性粒细胞检测ANCA受自身抗体的影响较大,甲醛固定的中性粒细胞受到的影响较小,同时应用猴肝切片可将这4种自身抗体与ANCA区别。结论:联合应用猴肝切片与乙醇和甲醛固定的中性粒细胞抗原片,有助于准确判断ANCA结果。

血清抗中性粒细胞胞质抗体阳性狼疮性肾炎患者的临床病理特征及预后

目的:回顾性分析血清抗中性粒细胞胞质抗体(ANCA)阳性狼疮性肾炎(LN)患者的临床、病理特征及预后。方法:收集本中心1985年1月至2008年12月间明确诊断为血清ANCA阳性LN患者,回顾性分析其临床、病理特征及预后,对照组选取同期诊断为血清ANCA阴性LN患者。结果:符合入选标准的49例患者中,38例MPO-ANCA阳性,7例PR3-ANCA阳性,4例MPO-ANCA和PR3-ANCA双阳性。女性40例、男性9例。中位年龄33岁。ANCA阳性LN患者,尿沉渣红细胞计数、血清肌酐、SLE-DAI评分均高于对照组(P<0.05);病理类型以LN-Ⅳ型为主,占61.22%;光镜下AI、CI评分均显著高于对照组(P<0.05)。ANCA阳性LN患者中,20例接受吗替麦考酚酸酯(MMF)诱导治疗,18例接受静脉环磷酰胺(CYC)诱导治疗,其余11例患者接受雷公藤多苷等治疗MMF组的完全缓解率(90.00%vs 55.56%,P=0.027)和肾脏生存率(P=0.039)均优于CYC组。ANCA阳性LN患者中位随访87.83月,有7例患者(14.29%)发生终末期肾病,均为MPO-ANCA阳性。结论:血清ANCA阳性LN患者肾脏表现为大量的血尿、肾功能损害明显。这部分患者接受MMF诱导治疗,其完全缓解率和肾脏预后均优于CYC。