ANCA阴性寡免疫复合物型新月体肾炎合并冷球蛋白血症一例

寡免疫复合物型新月体肾炎（pacuci—immunecrescenticglomerulonephritis，PICGN）是系统性小血管炎肾脏受累的主要表现，文献报道50％～80％的PICGN患者血清中可检测到抗中性粒细胞胞浆抗体（anti-neutrophilcytoplasmicantibodies，ANCA）。ANCA阴性的PICGN患者相对少，冷球蛋白血症患者肾脏易受累。本文报道一例ANCA阴性PICGN合并冷球蛋白血症。     

抗肾小球基底膜肾炎的发病机制

抗肾小球基底膜（glomerular basement mem brane,GBM）病是循环中的抗GBM抗体在组织中沉积所引起的一组自身免疫性疾病。肺、肾为主要受累的器官，如病变局限在肾脏称为抗GBM肾小球肾炎；当肺肾同时受累时称为Goodpasture综合征。临床可表现为肺出血和／或急进性新月体肾炎。多数患者起病急、病情进展快、预后差，急性肾衰竭是本病的主要死亡原因。     

非典型抗肾小球基底膜病1例并文献复习

<正>抗肾小球基底膜（glomerular basement membrane disease,GBM）病是一种罕见的小血管炎,其特征在于存在针对肾脏和（或）肺组织基底膜抗原的循环和沉积抗体[1]。新月体性肾小球肾炎和免疫荧光染色示免疫球蛋白（immunoglobulin,Ig）沿肾小球基底膜线样沉积为抗GBM     

ANCA相关性小血管炎肾损害的治疗

韦格纳肉芽肿（WG）、显微镜下型多血管炎（MPA）、Chury-Strauss综合征（CSS）和寡免疫复合物沉积型坏死性新月体肾炎（NCGN）发病机制与ANCA相关，目前统称为抗中性粒细胞胞浆抗体（ANCA）相关性小血管炎（ANCA-associated systemic vasculitis，AASV）。     

应用抗肾小球基底膜抗体的中和性单克隆抗体治疗抗肾小球基底膜肾炎大鼠的实验研究

目的 应用抗肾小球基底膜（GBM）抗体的中和性单克隆抗体注射抗GBM肾炎大鼠,观察各种生化指标及肾脏病理学的变化。 方法 将Wistar大鼠随机分为5组,每组9只：(1)肾炎模型组：经尾静脉注入人抗GBM抗体;(2)正常对照Ⅰ组:经尾静脉注入非抗体性的健康人lgG;(3)对照Ⅱ组：经尾静脉注入抗GBM抗体的中和性单克隆抗体;(4)干预Ⅰ组：经尾静脉注入人抗GBM抗体,第7天后再经尾静脉注入抗GBM抗体的中和性单克隆抗体(1.5 ml/100 g);(5)干预Ⅱ组：经尾静脉注入人抗GBM抗体,第14天后再经尾静脉注入抗GBM抗体的中和性单克隆抗体。分别在实验后第7、14、21天观察大鼠24 h尿蛋白量、BUN、Scr和肾组织病理学的变化。 结果 第21天干预Ⅰ组尿蛋白量为（16.62±5.53） g/d、BUN为（11.53±2.26） mmol/L、Scr为（102.46±16.86） μmol/L,均显著低于肾炎模型组（P < 0.05）;干预Ⅱ组较肾炎模型组也有所降低,但差异无统计学意义（P > 0.05）。干预Ⅰ组和干预Ⅱ组肾脏细胞增生、新月体的形成及免疫复合物的沉积均少于肾炎模型组,但干预I组更为明显。对照Ⅰ组和对照Ⅱ组之间无明显变化。 结论 早期应用抗GBM抗体的中和性单克隆抗体能够有效改善抗GBM肾炎大鼠的肾脏病变。     

以神经系统损害为首发症状伴血IgG4升高的抗中性粒细胞胞质抗体相关性血管炎一例

临床上以神经系统损害为首发症状的抗中性粒细胞胞质抗体（ANCA）相关性血管炎较为少见。本文报道1例以神经系统损害为首发症状,随后出现急进型肾炎综合征的ANCA相关性血管炎,血髓过氧化物酶抗体阳性且血IgG4明显升高。肾活检证实为寡免疫复合物性新月体肾炎。予糖皮质激素联合环磷酰胺诱导治疗后,患者神经系统症状、肾功能损害等...     

急骤进展性肾小球肾炎髓过氧化物酶的作用

急骤进展性肾小球肾炎髓过氧化物酶的作用［英］／Ｔａｋａｋｏｓａｅｋｉ…／／ＡｍＪＫｉｄｎｅｙＤｉｓ．－１９９５，２６（１）．－１３～２１系统性脉管炎和新月体性肾小球肾炎病人血清中有抗中性粒细胞质的自身抗体（ＡＮＣＡｓ）。髓过氧化物酶（ＭＰＯ）是急骤进...     

原发性急进性肾炎的治疗

原发性急进性肾炎 (ＲＰＧＮ)是一组临床表现相同 ,病理改变相似 ,病因与发病机理、免疫病理特征、临床经过和预后、对治疗的反应不尽相同的临床病理综合征。其共同的特征和诊断依据是 :肾小球肾炎伴快速进展的肾功能减退 ,在 3～ 6个月内肾小球滤过率下降 5 0 %以上 ;肾活检显示 5 0 %以上的肾小球有新月体形成。按免疫病理分类 ,ＲＰＧＮ可分为三型 :Ⅰ型———抗肾小球基底膜 (ＧＢＭ)抗体介导的ＲＰＧＮ ;Ⅱ型———免疫复合物型ＲＰＧＮ ;Ⅲ型———抗中性粒细胞胞浆抗体 (ＡＮＣＡ)相关性 (免疫缺少型 )ＲＰＧＮ。三种类型ＲＰＧＮ反…     

伴有免疫复合物沉积的ANCA相关性小血管炎患者临床及肾脏病理分析

目的：探讨有免疫复合物沉积的ANCA相关性小血管炎（AASV）患者临床及病理特点。方法：回顾性地分析近5年诊断明确并行肾活检的27例患者,根据免疫荧光及电镜分为有免疫复合物沉积组和少免疫复合物沉积组,均使用激素及免疫抑制剂治疗,比较两组的临床、病理特点及疗效、预后。结果：有免疫复合物沉积组14例,少免疫复合物沉积组13例。两组在年龄、性别、ANCA类型、起病至肾活检时间,发热、乏力等非特异性表现及肾外器官受累方面差异均无统计学意义。在血尿、高血压及血肌酐方面亦无明显差异,但有免疫复合物沉积组尿蛋白明显高于后者,差异有统计学意义。对激素及免疫抑制治疗的疗效及预后可能更差,但差异无统计学意义。在病理类型方面,两组均为新月体性肾炎,但有免疫复合物沉积组可合并IgA肾病和膜性肾病。结论：肾脏有免疫复合物沉积提示更多的尿蛋白,可能更差的疗效及预后,病理类型上在新月体性肾炎基础上合并IgA肾病和膜性肾病。     

ANCA相关性小血管炎发病机制研究进展

抗中性粒细胞胞浆抗体（anti-neutrophil cytoplasmic antibody,ANCA）相关性小血管炎（ANCA-associated systemic vasculitis,AASV）是一组以小血管壁的炎症和纤维素样坏死、血清中存在针对靶抗原蛋白酶3（PR3）或髓过氧化物酶（MPO）的ANCA阳性为主要特征的系统性自身免疫性疾病。它主要包括韦格纳肉芽肿（WG）、显微镜下多血管炎（MPA）、变应性肉芽肿性血管炎和特发性坏死性、新月体性肾小球肾炎（NCGN）。有关AASV的发病机制较为复杂，至今尚未完全阐明，但近年来相关的研究取得较大进展，现综述如下。     

Antigen-specific radioimmunoassays for anti-neutrophil cytoplasmic antibodies in the diagnosis of rapidly progressive glomerulonephritis.

Circulating anti-neutrophil cytoplasmic antibodies (ANCA) have been described in most patients with "pauci-immune" necrotizing and crescentic glomerulonephritis. A 29-kDa serine protease (p29 or proteinase 3) and myeloperoxidase are the two best characterized antigens recognized by ANCA. The study presented here was conducted to define the diagnostic value of assays for antibodies against these two antigens in rapidly progressive glomerulonephritis. Radioimmunoassays were developed for anti-p29 and anti-myeloperoxidase antibodies, with purified antigens, and the results of the radioimmunoassays were compared with those obtained by immunofluorescence tests for ANCA. We performed assays on serum samples from 123 patients with the syndrome of rapidly progressive glomerulonephritis, as well as from 200 blood bank donors and from 717 additional control patients. Without knowledge of the results of ANCA tests, the renal pathologic findings in the 123 patients with rapidly progressive glomerulonephritis were analyzed, and 42 were classified as pauci-immune necrotizing and crescentic glomerulonephritis, 18 were classified as anti-glomerular basement membrane nephritis and 63 were classified as other forms of renal disease. We found radioimmunoassays to be more reliable in the diagnosis of pauci-immune necrotizing and crescentic glomerulonephritis than immunofluorescence testing. By radioimmunoassay, ANCA were found in 40 of 42 patients (95% sensitivity) with pauci-immune necrotizing and crescentic glomerulonephritis (14 with anti-p29 and 26 with anti-myeloperoxidase antibodies). The tests for antibodies to p29 and myeloperoxidase were 99.9 and 99.5% specific for pauci-immune necrotizing and crescentic glomerulonephritis, respectively. In the setting of rapidly progressive glomerulonephritis, a positive radioimmunoassay for anti-p29 or anti-myeloperoxidase antibodies (together with a negative test for anti-GBM antibodies) gives a probability of pauci-immune necrotizing and crescentic glomerulonephritis of over 99%.     

Antineutrophil cytoplasmic autoantibody-negative Pauci-immune crescentic glomerulonephritis

Pauci-immune crescentic glomerulonephritis (CrGN) is one of the most common causes of rapidly progressive glomerulonephritis. The majority of patients with pauci-immune CrGN had circulating antineutrophil cytoplasmic autoantibody (ANCA). However, patients with ANCA-negative pauci-immune CrGN were not investigated fully. This study aimed to analyze the characteristics of this subgroup of patients. Patients whose pauci-immune CrGN was diagnosed from 1997 to 2006 in one center were studied retrospectively. The criteria of pauci-immune was defined as "the intensity of glomerular immunoglobulins staining by direct immunofluorescence assay in renal sections was negative to 1+ staining on a scale of 0 to 4+." Clinical and pathologic characteristics were compared between patients with and without ANCA. Among the 85 patients with pauci-immune CrGN, 28 (32.9%) were ANCA negative. Compared with the 57 ANCA-positive patients, the ANCA-negative patients were much younger (39.7 +/- 17.0 versus 57.6 +/- 14.0 yr; P < 0.001). The level of urinary protein and the prevalence of nephrotic syndrome were significantly higher in ANCA-negative patients than that in ANCA-positive patients (P < 0.01 and P < 0.001, respectively). However, the prevalence of extrarenal involvement was significantly lower in ANCA-negative patients than that in ANCA-positive patients. The renal survival was poorer in ANCA-negative patients than that in ANCA-positive ones (P < 0.05). ANCA-negative pauci-immune CrGN was not rare and might represent an independent disease entity from ANCA-positive vasculitis.     

Immune complex deposits in ANCA-associated crescentic glomerulonephritis: a study of 126 cases

BACKGROUND: Necrotizing and crescentic glomerulonephritis related to antineutrophil cytoplasmic autoantibodies (ANCA) is typically referred to as "pauci-immune"; however, it is not unusual for renal biopsies in such cases to exhibit some immune complex deposition within glomeruli on immunofluorescence and/or electron microscopic study. The composition and intraglomerular localization of such deposits in ANCA-glomerulonephritis has not been widely studied, and their potential pathologic and clinical significance is not clear, although a possible synergistic effect between immune complexes and ANCA in producing more severe glomerulonephritis is suggested by some human and animal studies. METHODS: Electron micrographs from 126 renal biopsies showing necrotizing/crescentic glomerulonephritis characterized by positive ANCA serology [C-ANCA, anti-proteinase 3 (anti-PR3), or anti-myeloperoxidase (MPO)] or necrotizing arteritis in the absence of known ANCA results were examined for the presence, quantity, and location of electron-dense deposits. The presence or absence of such deposits was correlated with histologic findings (fraction of glomeruli with crescents and segmental necrotizing lesions, mesangial and endocapillary hypercellularity), immunofluorescence findings, and clinical data, including serum creatinine and 24-hour urine protein levels at the time of biopsy. RESULTS: Sixty-eight (54%) of these biopsies showed glomerular immune complex deposits on electron microscopy; 87% of the latter also showed positive immunofluorescence findings for at least one immunoglobulin or complement component, although staining was relatively mild in most instances (< or =2+ on a 0 to 4+ scale in all but eight cases). Nearly half of biopsies negative for deposits by electron microscopy also showed positive immunofluorescence findings, though even more so than in cases with deposits on electron microscopy the intensity of immunofluorescence staining in these biopsies was typically very weak (trace or trace to 1+ in most cases, none >2+). Hypercellularity within the glomerular tuft was seen in 50% of biopsies with deposits on electron microscopy but only 14% of those without deposits; in each group this was usually mild and mesangial. Notably, the presence of deposits on electron microscopy was associated with a higher median level of proteinuria (3.2 versus 1.3 g/24 hours, P < 0.0001) and a higher median percentage of glomeruli with crescents (62.5% versus 44.0%, P= 0.06). CONCLUSION: Immune complex deposits were found on electron microscopy in just over half of renal biopsies with crescentic glomerulonephritis associated with positive ANCA serology and/or necrotizing arteritis. Clinical correlations suggest that these immune complex deposits may somehow potentiate the effect of ANCA in producing glomerulonephritis.     

Azurocidin-specific-ANCA-related idiopathic necrotizing crescentic glomerulonephritis

An 80-year-old woman who had rapidly progressive glomerulonephritis unaccompanied by systemic vasculitis is described. On renal biopsy, she showed necrotizing crescentic glomerulonephritis by light microscopy and pauci-immune glomerular lesions by immunofluorescent study. No dense deposits were present on electronmicroscopic study. On serum examination, indirect immunofluorescent study showed perinuclear pattern antineutrophil cytoplasmic antibody (ANCA), but myeloperoxidase-ANCA and proteinase 3-ANCA were both negative. Her serum reacted only to azurocidin excluding other ANCA antigens: bactericidal permeability-increasing protein, cathepsin G, elastase, lactoferrin, or lysozyme. Serum creatinine level decreased, and C-reactive protein turned negative after steroid therapy. Azurocidin-ANCA also turned negative. It is suggested that azurocidin-ANCA might have been related to the inflammatory process of pauci-immune necrotizing crescentic glomerulonephritis in this patient.     

肾脏有免疫复合物沉积的小血管炎的临床病理特点

目的 回顾性总结分析肾脏有免疫复合物沉积的ANCA相关系统性血管炎(AASV)患者的临床和病理特点。方法 将近5年在北京大学第一医院住院诊断为AASV且肾活检免疫荧光显示系膜区有免疫复合物沉积(免疫球蛋白≥++)的患者与同期少免疫复合物沉积的患者的临床和病理进行比较。结果 肾脏有免疫复合物沉积者8例(IgM沉积5例,IgA沉积2例,IgG沉积1例),肾脏少免疫复合物沉积者32例。2组在性别、年龄、ANCA类型、起病至肾活检的时间、临床表现以及短期肾脏存活率方面差异均无显著性意义,仅前组患者在有前驱感染方面显著多于后组(P<0.05)。结论 肾脏有免疫复合物沉积的AASV的临床与病理特点与普通的AASV基本一致,应引起高度重视,而需要针对AASV的强化免疫抑制治疗。     

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.     

Clinical and pathologic characteristics of pauci-immune anti-myeloperoxidase antibody associated glomerulonephritis with nephrotic range proteinuria

Background: Heavy proteinuria in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is usually considered to be associated with immune deposits in renal biopsy. Nephrotic ANCA GN without immune deposits (pauci-immune) is rare and has not been studied specially. In this study characteristics of these patients are to be investigated.

Methods: Clinical and pathological characteristics from 20 kidney biopsy-proven pauci-immune anti-myeloperoxidase antibody-associated GN patients with nephrotic proteinuria were analyzed and were compared with ANCA GN patients without nephrotic proteinuria.

Results: Acute kidney injury (AKI) and gross hematuria were much prevalent but extra-renal involvement was less prevalent in pauci-immune ANCA GN with nephrotic proteinuria than in pauci-immune ANCA GN without nephrotic proteinuria. No more severe hypoalbuminemia, hypercoagulability, hyperlipidemia or higher thrombosis incidence were found between two groups. Compared with patients without nephrotic proteinuria, patients with nephrotic proteinuria had more prevalent crescentic category in histopathology. Proteinuria decreased quickly after treatment but much poorer renal prognosis was found in pauci-immune ANCA GN with nephrotic proteinuria. The results of urinary albumin to total protein ratio and urinary protein electrophoresis showed pauci-immune ANCA GN with nephrotic proteinuria had obvious non-selective proteinuria.

Conclusions: Pauci-immune ANCA GN with nephrotic proteinuria do not have more severe hypoalbuminemia, hypercoagulability or hyperlipidemia than patients without nephrotic proteinuria. Non-selective proteinuria might be the reason. However, pauci-immune ANCA GN with nephrotic proteinuria have more prevalent crescentic category in histopathology, higher incidence of AKI, gross hematuria and poorer renal prognosis despite of good sensitivity to therapy of proteinuria.     

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.     

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.