The clinical features of anti-neutrophil cytoplasmic antibody-associated systemic vasculitis in Chinese children

Anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis is reported mainly in adults. Studies in children are limited. The current study retrospectively analyzed the clinical characteristics and pathology of ANCA-associated systemic vasculitis in children in our hospital during the past 7 years. Twenty-four pediatric patients were diagnosed as having ANCA-associated systemic vasculitis, including 19 patients with microscopic polyangiitis (MPA), one with Wegener’s granulomatosis (WG), three with propylthiouracil (PTU)-induced ANCA-positive vasculitis and one with anti-glomerular basement membrane (GBM) disease. Of patients with primary ANCA-associated systemic vasculitis (MPA and WG), with an average age of 10.8±2.8 (6–14) years, 18 patients (90%) were female and two (10%) were male. Nineteen patients (95%) were p-ANCA/MPO-ANCA positive and one (5%) was c-ANCA/PR3-ANCA positive. The interval between onset and diagnosis was 8.5±24.3 (0.2–108) months. The majority of the patients (85%) had multi-organ involvement. All patients had clinical evidence of renal involvement and presented with hematuria and proteinuria. Of 20 patients, 16 (80%) also had acute renal failure, and five patients were dialysis dependent. Nine patients underwent renal biopsy and were diagnosed with necrotizing and crescentic glomerulonephritis. However, six biopsies showed immune complex deposition. All patients received immunosuppressive therapy including prednisone and cyclophosphamide, and ten patients also received intravenous administration of methylprednisone pulse therapy according to their clinical situation and renal pathology. Sixteen patients achieved clinical remission, and four patients presented as treatment failure. Patients were followed up for 12.3±5.1 months (median 12 months; range 1 to 91 months). Ten patients maintained their clinical remission, and ten progressed to renal failure requiring dialysis. Our study showed that the clinical features and pathology of primary ANCA-associated systemic vasculitis in children were similar to those of adults, but there were a predominance of female patients and late diagnoses. We suggest that early recognition and prompt aggressive treatment might improve outcome.     

ANCA-associated vasculitis with renal involvement: an outcome analysis.

BACKGROUND: The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are a group of heterogeneous diseases. This study was undertaken to investigate the outcome of Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and renal-limited vasculitis (RLV). Furthermore, we analysed the differences in patients with proteinase 3-ANCA (PR3-ANCA) and those with myeloperoxidase-ANCA (MPO-ANCA), which have not been assessed in a homogeneously treated group of patients with renal involvement. METHODS: In this retrospective analysis, 80 patients with a new diagnosis of WG, MPA or RLV with biopsy-proven renal involvement were followed over a median of 46.7 months (range: 0.8-181.9 months). All patients had induction treatment with cyclophosphamide and oral corticosteroids. RESULTS: At the end of follow-up, 23% were dependent on dialysis. Renal survival was significantly worse in patients with WG compared with patients with MPA or RLV (P = 0.04). A higher rate of end-stage renal disease (ESRD) was noticed in PR3-ANCA- vs MPO-ANCA-positive patients. A total of 21 patients (26%) died. Predictors of patient mortality were development of ESRD, older age and the maximum creatinine in the first month. Mortality was found to be higher in patients with WG and was significantly higher in PR3-ANCA-positive cases (P = 0.02). The relative risk of death was 9.32 times higher in PR3-ANCA- vs MPO-ANCA-positive patients. CONCLUSIONS: Our data underscore the pathogenetic potential of ANCA by demonstrating a more aggressive disease state and a poorer outcome in patients with PR3-ANCA.     

ANCA-associated vasculitis: report from Korea

We investigated the clinical features of Korean patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) by reviewing the literature. The characteristics of AAV in Korean patients were as follows: (1) granulomatous and limited disease is prevalent in granulomatosis with polyangiitis (Wegener’s) (GPA), (2) ANCA positivity is lower in GPA (56.6–68.9 %) and eosinophilic granulomatosis with polyangiitis (EGPA) (5.9–8.3 %), whereas it is higher in microscopic polyangiitis (MPA) (69–94 %), (3) C-ANCA/proteinase 3 (PR3)-ANCA positivity is 71.5–100 % in GPA and P-ANCA/myeloperoxidase (MPO)-ANCA positivity reached 94–100 % in patients with MPA, (4) renal involvement or progression to end-stage renal disease was lower in Korean patients with GPA and EGPA than in Caucasians with GPA and EGPA (according to data provided in reports). The data provided here may need to be confirmed in large-scale studies.     

Mycophenolate mofetil versus cyclophosphamide for inducing remission of ANCA vasculitis with moderate renal involvement.

OBJECTIVE: We performed a single-centre non-blinded clinical trial to compare the clinical efficacies of mycophenolate mofetil (MMF) and intermittent cyclophosphamide (CTX) pulse therapy as induction treatments in patients with antineutrophil cytoplasmic antibody (ANCA) vasculitis (AAV) and moderate renal involvement. METHODS: Patients with active AAV and serum creatinine <500 micromol/L received either MMF treatment (MMF group) or monthly CTX pulse therapy (CTX group) for 6 months. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). The disease activity, remission rate, renal function and adverse reactions were compared between the two groups. RESULTS: A total of 35 patients (15 male, 20 female: aged 49.1 +/- 12.2 years) were enrolled, with 18 in the MMF group and 17 in the CTX group. Of the 35 patients, 28 were MPO-ANCA positive and 2 were PR3-ANCA positive. Four patients were lost to follow-up in the CTX group. At Month 6, BVAS scores were much lower in the MMF group than in the CTX group (0.2 +/- 0.89 versus 2.6 +/- 1.7, P < 0.05). In the intent-to-treatment analysis, 14 of 18 patients (77.8%) treated with MMF and 8 of 17 patients receiving CTX (47.1%) had complete remission with an absolute difference of 30.7%. Eight of 18 patients (44.4%) in the MMF group and 2 of 17 patients (15.4%) in the CTX group recovered renal function. Serum ANCA decreased to normal in 41.7% of patients in the MMF group and in 16.7% in the CTX group. Side effects in the MMF group were pneumonia (1), herpes zoster (1) and gastrointestinal symptoms (2), and in the CTX group were leukocytopenia (1), gastrointestinal distress (4) and pneumonia (1). CONCLUSION: Our study suggests that MMF effectively ameliorates disease activity and considerably improves renal function in patients with AAV. Further large-scale multicentre prospective randomized controlled trials will be needed to confirm these findings.     

Clinical significance of anti-neutrophil cytoplasmic antibodies (ANCA) in collagen diseases associated with vasculitic syndrome in Japan.

The present study was undertaken to determine the anti-neutrophil cytoplasmic antibody (ANCA) levels in 96 patients with various collagen diseases associated with renal vasculitis and vasculitic syndrome in Japan. The results indicated that cytoplasmic(C)-ANCA is an autoantibody highly specific to Wegener's granulomatosis (WG) and that it is also active in renal injury. The relationships between ANCA and focal segmental necrotizing GN, i.e., renal vasculitis as proposed by Balow, were investigated. Perinuclear(P)-ANCA was detected with high sensitivity and specificity in renal vasculitis without WG, and the severity of necrotizing and crescentic nephritis in WG was correlated especially well with the C-ANCA titer. Detection of ANCA is considered clinically useful for the etiological differentiation of renal vasculitis, suggesting the possibility that C-ANCA may be involved in the onset of vasculitis of the glomerular capillary vessels in WG. The presence of C-ANCA and cytokines (IL-1 beta and TNF-alpha) is important in the pathogenesis of vasculitis and GN in WG.     

抗髓过氧化物酶抗体阳性的韦格纳肉芽肿病的特点

目的 分析抗髓过氧化物酶(MPO)抗体阳性的韦格纳肉芽肿病(WG)患者的临床病理特点及其与传统的抗蛋白酶3(PR3)抗体阳性者之间的差异&#65377;方法 89例WG患者经本院肾内科确诊,分析其临床病理资料并对比抗MPO抗体阳性和抗PR3抗体阳性的两组患者之间的差异&#65377;结果 89例患者中54例抗MPO抗体阳性,34例抗PR3抗体阳性&#65377;抗MPO抗体阳性患者中男性所占的比例显著低于抗PR3抗体阳性者(男:女分别为23:31与24:10, P<0.05)&#65377;抗MPO抗体阳性的WG临床亦呈多器官受累的表现,其中关节痛&#65380;皮疹&#65380;眼&#65380;耳受累的发生率显著低于抗PR3抗体阳性者(分别为46.3%比70.6%,P < 0.05; 20.4%比44.1%,P < 0.05;27.8%比58.8%,P < 0.01和40.7%比67.6%,P < 0.05);伯明翰血管炎活动度积分(BVAS)显著低于抗PR3抗体阳性者(22.2±6.2比24.7±6.9, P < 0.05);而在确诊时Scr增高的发生率则显著高于抗PR3抗体阳性者(81.5%比61.8%, P < 0.05)&#65377;结论 在国人的WG患者中,抗MPO抗体阳性者可能不占少数,它与抗PR3抗体阳性者临床表现有所不同&#65377;     

Vasculite c-ANCA relacionada em paciente com retocolite ulcerativa: relato de caso*

The pulmonary manifestations of ulcerative colitis (UC) are rare and include inflammation of small and large airways, parenchymal disease and serositis among others. A substantial proportion of patients with inflammatory bowel disease, particularly those with ulcerative colitis presents positive ANCA, most p-ANCA pattern. We present a case of patient with ulcerative colitis, with positive c-ANCA, which progressed to hemoptysis associated with radiological findings consistent with pulmonary vasculitis.     

ANCA相关性血管炎肾损害临床特征及早期诊治探讨

目的 分析抗中性粒细胞胞浆抗体(ANCA)相关性血管炎的临床表现和肾脏病理特征,探讨早期诊断和治疗对预后的影响.方法选取本院2000年1月至2009年8月明确诊断的ANCA相关性血管炎共21例,18例行肾活检.总结患者的临床病理资科.分析不同治疗时机对肾功能转归的影响.结果本组21例ANCA相关性血管炎平均年龄(52.5±11.5)岁,显微镜下多血管炎(MPA)16例,韦格纳肉芽肿(WG)3例,变应性肉芽肿性血管炎(CSS)2例.肾外表现主要为发烧17例(80.1%)、下呼吸道症状18例(85.7%)、肺影像学改变21例(100%)、贫血16例(76.2%)、眼耳鼻受累8例(38.1%);肾脏表现血尿21例(100%),蛋白尿19例(90.1%),血肌酐正常6例(28.5%),升高15例(71.4%),8例需透析替代.ANCA检测pANCA和MPO-ANCA阳性16例,cANCA和PR3-ANCA阳性3例.pANCA/MPO-ANCA和cANCA/PR3-ANCA均阳性1例,全阴性1例.肾活检可见节段性小血管壁纤维素样坏死,新月体多见.免疫荧光无或微量免疫复合物沉积.治疗采用糖皮质激素联合环磷酰胺,重症加用血浆置换.7例血肌酐异常但不需透析者5例治疗后血肌酐恢复正常;8例需透析者2例治疗后血肌酐恢复正常,2例脱离透析但血肌酐异常,4例未能脱离透析.结论ANCA相关性小血管炎临床表现多样,肺、肾是最常见的受累器官.ANCA检测和肾活检有助于早期诊断,尽早积极治疗有助于肾功能的恢复.     

100例新月体肾炎的免疫病理分型及临床病理分析

目的：了解新月体性肾炎的免疫病理分型及其临床病理特点。方法：对我科近10年来经肾活检确诊的100例新月体性肾炎进行回顾性分析,对患者血清进行抗中性粒细胞胞浆抗体（ANCA）和抗肾小球基底膜（GBM）抗体的检测。结果：100例患者中21％为抗GBM抗体型,其中6／21例同时合并ANCA阳性;47％为免疫复合物型,其中9／47型ANCA阳性;32％为少免疫沉积型,其中17／32例为ANCA阳性小血管炎。3种类型相比,抗GBM抗体型以青年男性为主,多有少尿或无尿（P＜0．05）,肾小球受累受为广泛（P＜0．001）,预后差（P＜0．001）。免疫复合物型以中青年为主,多表现为肾病综合征（P＜0．01）,强化免疫抑制治疗有效。少免疫沉积型以中老年为主,有多系统受累（P＜0．05）,治疗效果相对较好。结论：我国新月体肾炎中虽仍以免疫复合物型为主,但抗GBM抗体型和ANCA阳性小血管炎并不少见。肾活检免疫病理和血清自身抗体的联合应用对新月体肾炎进行分类更接近病因学诊断。     

抗中性粒细胞胞浆抗体相关性小血管炎30例临床诊治分析

目的：探讨抗中性粒细胞胞浆抗体（ANCA）相关性小血管炎的临床特点、诊断和治疗。方法：回顾性分析2002年6月~2009年6月检测并明确诊断的30例ANCA相关性小血管炎患者的临床病理资料。结果：30例患者中胞浆型ANCA（c-ANCA）阳性4例,3例识别蛋白酶3（PR3）,1例识别髓过氧化物酶（MPO）;核周型ANCA（p-ANCA）阳性26例,均识别MPO。临床表现呈多器官受累,以肾、肺受累为主。多数患者有贫血、血沉增快和C反应蛋白增高。糖皮质激素联合免疫抑制剂治疗,诱导缓解的缓解率为83.3%。结论：ANCA相关性小血管炎临床表现为多器官受累,缺乏特异性,其诊断要结合临床表现、ANCA检测和病理活检综合考虑,糖皮质激素联合免疫抑制剂治疗有较好疗效,吗替麦考酚酯和硫唑嘌呤等免疫抑制剂较环磷酰胺毒副作用更小。     

Retrospective study of 97 ANCA-positive patients: epidemiologic and clinical spectrum

We analysed the clinical profile of antineutrophil cytoplasmic antibodies (ANCA) positive patients in a retrospective study including all cases of ANCA positivity (determined by ELISA) from the Nephrology Clinic, Parhon University Hospital Iasi during the interval 1998-2003. There were 97 ANCA positive patients (mean age 43.7 ?18-75? years, female/male ratio 1.55), of whom almost two thirds had c-ANCA, almost one third p-ANCA, while 9 patients had both types of antibodies. The incidence was 22.5/pmp for the North-Eastern province of Romania. Just 19.3% from the suspected cases with ANCA-associated disease were positive for these antibodies. 47.7% had systemic vasculitis (10 with microscopic polyangiitis--MA, 6 with Wegener's granulomatosis--WG, 1 with Churg-Strauss angiitis, 29 with non-specific vasculitis--NSV). Twenty-seven (27.8%) had connective tissue disease--CTD (systemic lupus erythematosus, rheumatoid arthritis, polymyositis, systemic sclerosis, mixed connective tissue disease, and sarcoidosis), while in 5 cases ANCA were associated with other diseases. Nine cases presented with rapid progressive glomerulonephritis (RPGN) without signs of systemic involvement, and other ten with advanced chronic renal failure (CRF). The most frequent clinical manifestations involved the kidney (71%), the skin, the muscles and joints, and the cardiovascular system. CONCLUSIONS: ANCA positivity is associated with a wide spectrum of diseases, mostly with CTD and NSV. c-ANCA was predominantly seen in WG and advanced CRF, while p-ANCA was associated with MA. In nonspecific vasculitis and connective tissue diseases, both patterns were present. We recommend ANCA determination as a screening method in all cases with renal dysfunction and nephritic syndrome and/or with signs of systemic vasculitis and/or collagenosis.     

Clinical implications of antineutrophil cytoplasmic antibody test in lupus nephritis

To elucidate the prevalence and clinical implications of antineutrophil cytoplasmic antibody (ANCA) in lupus nephritis (LN), we examined ANCA by indirect immunofluorescence and by ELISA against antilactoferrin (anti-LF) and antimyeloperoxidase (anti-MPO) antibody. To discriminate perinuclear ANCA (pANCA) with antinuclear antibody (ANA), all the ANCA-positive sera were tested again after incubating patients' sera with single-stranded (SS) and double-stranded (ds) DNA. These results were compared with clinicopathologic manifestations and clinical courses of LN. ANCA was positive in 19 (37.3%) of 51 LN patients. Among these LN patients, 3 had cytoplasmic ANCA (cANCA) and 16 had pANCA. ANCA was not found in 8 SLE patients without nephritis and 30 normal controls. The presence of ANCA, particularly pANCA, was associated with the presence of nephritis (18/51 cases vs. 0/8 cases, p < 0.05), especially with diffuse proliferative lupus nephritis, WHO class IV (17/18 cases vs. 21/31 cases, p < 0.05) as well as the presence of anti-dsDNA antibody (17/19 cases vs. 18/30 cases, p < 0.05). Patients with ANCA frequently had deterioration of renal function (3/16 vs. 0/26 cases). Anti-LF antibody was positive in 13 patients. Among those, 12 patients had nephritis. Five patients with anti-LF antibody did not have ANCA, but 7 had pANCA, and 1 had cANCA. Patients with anti-LF antibody had lower initial creatinine levels than those without it [serum creatinine (mg/dl): 0.78 (0.6-1.0) vs. 1.43 (0.5-5.0), p < 0.05]. Anti-MPO antibody was positive in only 1 patient, suggesting that MPO is a rare antigen for ANCA in LN.     

Risk of acute myocardial infarction,stroke, and venous thromboembolism among patients with anti-neutrophil cytoplasmic antibody-associated vasculitis in South Korea: A nationwide population-based study

ObjectivesTo investigate the incidence and risk of cerebro-cardiovascular comorbidities (stroke, acute myocardial infarction, venous thromboembolism, and pulmonary embolism) in anti-neutrophil cytoplasmic antibody-associated vasculitis using nationwide Korean population-based medical claims data.MethodsWe identified 1905 patients with newly diagnosed anti-neutrophil cytoplasmic antibody-associated vasculitis during 2009–2019. Incidence rates and hazard ratios with 95% confidence intervals were calculated to estimate the risk of cerebro-cardiovascular comorbidities in these patients and compared to age- and sex-matched controls (1:10) using the Cox proportional hazards model.ResultsMost patients had microscopic polyangiitis (42.5%), followed by granulomatosis with polyangiitis (29.1%) and eosinophilic granulomatosis with polyangiitis (28.4%). The annual incidence rate of anti-neutrophil cytoplasmic antibody-associated vasculitis in 2019 was 0.55 per 100,000 person-years. Cerebro-cardiovascular comorbidities occurred in 12.6%. Stroke was most common (64.6%), followed by venous thromboembolism (34.6%), pulmonary embolism (18.3%), and acute myocardial infarction (5.4%). Korean patients with anti-neutrophil cytoplasmic antibody-associated vasculitis were at a significantly (2.3 times) higher overall risk for cerebro-cardiovascular comorbidities than the general population (adjusted hazard ratios, 4.5, 3.1, and 2.0 times higher for pulmonary embolism, venous thromboembolism, and stroke, respectively). These findings were similar for patients with each subtype of anti-neutrophil cytoplasmic antibody-associated vasculitis.ConclusionsThis is the first nationwide population-based study to demonstrate a significant risk of cerebro-cardiovascular comorbidities as complications of anti-neutrophil cytoplasmic antibody-associated vasculitis in Korean patients. Knowing these risks may enable personalized patient care and improve overall survival.     

Clinical significance of autoantibodies against neutrophil cytoplasmic components in patients with renal disease

The diagnostic significance of anticytoplasmic autoantibodies (ANCA) was studied in 71 renal patients. The ANCA test was positive in 67% of patients with Wegener's granulomatosis (WG), in 35% of those with a simultaneous renal and respiratory tract disease but not diagnosed as WG and in 22% of patients with a renal disease associated with unspecific collagenosis/vasculitis. Among WG patients ANCA positivity clearly correlated with the presence of active renal disease. Interestingly, both ANCA-positive and -negative patients were encountered in the group with acute renal failure and acute extracapillary glomerulonephritis associated with diffuse pulmonary infiltrates. The diagnostic and clinical significance of the ANCA test in these cases remains for the present obscure. In the majority of the ANCA-positive renal patients with respiratory tract abnormalities, the antibodies showed diffuse cytoplasmic staining and were mostly of the IgG class, of both IgG and IgM classes in some cases and of IgG, IgM and IgA classes in 1 patient. In patients with unspecific vasculitis/collagenosis the level of ANCA was rather low, and the distribution of different isotypes resembled that of patients with respiratory symptoms. A certain isotype of ANCA or staining pattern did not mark out any clinicopathologic subgroup among the patients. Our findings indicate that the clinical picture of ANCA-positive patients varies considerably and the ANCA test may not be as specific a marker of WG as previously suggested.     

Antineutrophil cytoplasmic antibodies (ANCA) in Chinese patients with anti-GBM crescentic glomerulonephritis

OBJECTIVE: To study the prevalence of ANCA and their target antigen in Chinese patients with anti-GBM crescentic glomerulonephritis (CGN), and to evaluate the possible role of ANCA in Chinese anti-GBM CGN patients with coexisting serum ANCA by studying clinicopathologic features of this disease. MATERIAL AND METHODS: Twenty-three sera were collected from 23 renal biopsy-proven anti-GBM CGN patients. According to the standardized procedures, all of the sera were determined by both, indirect immunofluorescence (IIF) ANCA, and enzyme-linked immunosorbent assay (ELISA) MPO-ANCA, PR3-ANCA and BPI-ANCA. The patients were divided into two groups according to serum ANCA positivity (Group A) or negativity (Group B). Thirty-three ANCA-associated pauci-immune CGN patients were regarded as control group (Group C). Their clinicopathologic features were compared to reveal whether ANCA correlated with disease activity. RESULTS: There were 11 (47.8%) cases with positive serum ANCA in 23 anti-GBM glomerulonephritis patients. There were 4/11 MPO-ANCA (one with positive PR3-ANCA and C-ANCA, three with negative IIF-ANCA), 1/11 PR3-ANCA (with positive MPO-ANCA and C-ANCA), 3/11 P-ANCA (with negative ELISA-ANCA) and 5/11 C-ANCA (one with positive PR3-ANCA and MPO-ANCA, and the other four with negative ELISA-ANCA). No BPI-ANCA was detected. No different clinicopathologic features were found between Groups A and B. Both were different from Group C in age, sex ratio, frequence of anuria and ESRD, variety of crescents, glomerular sclerosis, vessel lesion and prognosis. CONCLUSION: Our data demonstrate that ANCA in Chinese patients with anti-GBM CGN is not rare. The major target antigen of ANCA is MPO. ANCA seems not to be correlated with disease activity.     

Otolaryngologic manifestations of antineutrophil cytoplasmic antibody-associated vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterized by systemic necrotizing vasculitis, and patients fall into 2 groups: those with proteinase 3-ANCA and those with myeloperoxidase-ANCA. As infections are a trigger of ANCA-associated vasculitis, this disease tends to localize in areas around the upper airway. In this study, the authors compared ear and nasal symptoms between patients with proteinase 3-ANCA and those with myeloperoxidase-ANCA. We undertook a retrospective case series study of 34 patients diagnosed with ANCA-associated vasculitis. The otologic symptoms were divided into 3 types: chronic otitis media, secretory otitis media, and sensorineural hearing loss. Chronic otitis media was more common in patients with proteinase 3-ANCA (P = .001), whereas secretory otitis media was more frequently found in patients with myeloperoxidase-ANCA (P = .007). Crust formation (P = .001), saddle nose (P = .024), and sinusitis (P = .001) were more common in patients with proteinase 3-ANCA than in those with myeloperoxidase-ANCA. Marked differences were observed in the disease spectrum between the 2 ANCA groups.     

Myeloperoxidase anti‐neutrophil cytoplasmic antibody affinity is associated with the formation of neutrophil extracellular traps in the kidney and vasculitis activity in myeloperoxidase anti‐neutrophil cytoplasmic antibody‐associated microscopic polyangiitis

Anti‐neutrophil cytoplasmic antibody (ANCA) is associated with small‐vessel vasculitis particularly in the kidneys and can induce the formation of neutrophil extracellular traps (NETs) from primed neutrophils. Recently we have reported that the induction of NETs correlates with ANCA affinity for myeloperoxidase (MPO) and disease activity in patients with MPO‐ANCA‐associated microscopic polyangiitis. To investigate whether MPO‐ANCA affinity is associated with the formation of NETs in vivo, we examined the occurrence of NETs in the renal tissues of patients with MPO‐ANCA‐associated microscopic polyangiitis and ANCA affinity by double immunofluorescence staining for NET components of citrullinated histone, MPO and PAD4 and by ELISA competition with MPO, respectively. We divided 30 MPO‐ANCA‐associated microscopic polyangiitis patients into 2 groups based on their ANCA affinity levels (IC₅₀ for the high: 0.11 ± 0.04 µg/mL (Group1) and IC₅₀ for the low: 0.66 ± 0.24 µg/mL (Group2)). Group1 showed a higher Birmingham vasculitis activity score (15.6 ± 5.7) and 73% of the patients presented clinically with rapidly progressive glomerulonephritis and histologically with focal/crescentic glomerulonephritis (GN). Group 2 showed a lower Birmingham vasculitis activity score (9.2 ± 4.9) and 73% of the patients presented clinically with chronic renal failure and histologically with mixed/sclerotic GN. Group 1 showed a much higher occurrence of NETs than Group 2. Our findings indicate that ANCA affinity was associated with the in vivo formation of NETs, which might be involved in the pathophysiology of patients with MPO‐ANCA‐associated microscopic polyangiitis.     

Renal survival and prognostic factors in patients with PR3-ANCA associated vasculitis with renal involvement

BACKGROUND: Severe renal disease is a feature of anti-neutrophil cytoplasmic antibodies (ANCA)-associated small-vessel vasculitis. We evaluated patient and renal survival and prognostic factors in patients with PR3-ANCA associated vasculitis with renal involvement at diagnosis during long-term follow-up. METHODS: Eighty-five patients were diagnosed between 1982 and 1996 and followed until 2001 allowing >or=5 years of follow-up. All patients were treated with prednisolone and cyclophosphamide. Univariate and multivariate analyses with patient and renal survival as dependent variables were performed. RESULTS: Of the 85 patients in this study, 17 (20%) died within one year after diagnosis. Of the 25 patients (29%) who were dialysis dependent at diagnosis, two remained dependent and two again became dialysis dependent after less than one year; nine died early without renal recovery. Risk factors for death occurring within one year in univariate analysis (RR, 95% CI) were age>65 years (6.5, 1.6-13.7) and dialysis dependency at diagnosis (3.6, 1.0-13). Twenty patients died beyond one year during the long-term follow-up. Male gender (4.7, 1.6-10) and developing dialysis dependency during follow-up (4.1, 1.4-12) were associated with poor outcome. Risk factor for renal failure within one year was dialysis dependency at diagnosis (29, 3.6-229). Of 64 patients dialysis independent one year after diagnosis, 12 patients became dialysis dependent during follow-up. A renal relapse was strongly associated with development of renal failure in long-term follow-up (17, 3.5-81). CONCLUSIONS: Early death and failure to recover renal function in PR3-ANCA associated vasculitis is associated with age> 65 years and dialysis dependency at diagnosis. Long-term renal survival is determined by renal relapses during follow-up only. Slow, progressive renal failure without relapses is rarely observed in this group.     

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 anti-GBM glomerulonephritis patients were collected and were tested for ANCA respectively. Characteristics and outcome of patients with coexisting anti-GBM antibody and ANCA were analyzed, and were compared with anti-GBM glomerulonephritis patients without coexisting ANCA. Results Among the 23 sera with anti-GBM antibody, 7 sera had coexisting ANCA (7 MPO-ANCA, 1 PR3-ANCA), which represented 30.4% of the anti-GBM glomerulonephritis patients. The incidence of hemoptysis and hematuria in ANCA+-anti-GBM glomerulonephritis group was significantly higher than that in ANCA--anti-GBM glomerulonephritis group (P＜0.05). No significant difference in age, sex, other clinical manifestations and pathological features were found between patients with and without coexisting serum ANCA. Conclusion The incidence of hemoptysis and hematuria in ANCA+-anti-GBM glomerulonephritis group is significantly higher than that in ANCA--anti-GBM glomerulonephritis group, but the prognoses of the two groups were poor.     

Antineutrophil cytoplasmic antibody-negative pauci-immune crescentic glomerulonephritis associated with rheumatoid arthritis: An unusual case report

Clinically relevant renal lesions in rheumatoid arthritis (RA) are not common. More often renal involvement is related to complications of therapy than the disease itself. The most common forms of primary renal disease in RA are membranous glomerulonephropathy and a pure mesangial proliferative glomerulonephritis. Some studies have described the association between crescentic glomerulonephritis (crescentic GN) and RA, but they were all found to be perinuclear antineutrophil cytoplasmic antibody (p-ANCA) positive. However, RA associated with ANCA negative pauci-immue crescentic GN has not been reported. This is a case report of a 37-year-old female with RA who initially presented with general oedema and acute deterioration of renal function. The renal biopsy revealed ANCA negative pauci-immune crescentic GN. The patient was treated with steroid pulse and plasmapheresis, but not cyclophosphamide because of severe urosepsis. Despite the use of aggressive therapy, her renal function was not improved and she underwent maintenance haemodialysis thereafter. Because ANCA negative crescentic GN may occur in RA patients without frank systemic vasculitis, but with severe clinical manifestation, a heightened suspicion for a relatively 'silent' crescentic GN would have led to the correct diagnosis and appropriate treatment.