Haas M, Jafri J, Bartosh S M, Karp S L, Adler S G, Meehan S M
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Am J Kidney Dis. 2000 Oct;36(4):709-18. doi: 10.1053/ajkd.2000.17615.
Antineutrophil cytoplasmic autoantibodies (ANCA) are commonly associated with a necrotizing and crescentic glomerulonephritis (GN) that is pauci-immune, with few or no glomerular immune complex deposits detectable by immunofluorescence (IF) or electron microscopy (EM). Immunoglobulin A (IgA) nephropathy may also be manifest as a crescentic GN, but it is characterized by mesangial immune complex deposits containing IgA and is rarely associated with myeloperoxidase (MPO)- or proteinase 3 (PR3)-specific ANCA when an enzyme immunoassay is used to detect these antibodies. This report describes six patients with severe crescentic GN with mesangial IgA deposits by IF and mesangial electron-dense deposits by EM in patients with positive ANCA serological test results (four patients, anti-PR3; one patient, anti-MPO; one patient, anti-PR3 and anti-MPO). Patients presented with acute or progressive renal insufficiency, hematuria, proteinuria (nephrotic range in two patients), and hypertension. Three patients had evidence of systemic vasculitis: two patients at initial presentation and one patient later in the clinical course. Renal biopsy specimens showed crescents in greater than 50% of glomeruli in all cases, but only mild, focal and segmental mesangial and endocapillary hypercellularity, more typical of ANCA-associated crescentic GN than of crescentic IgA nephropathy without associated ANCA. Semiquantitative analysis of mesangial and endocapillary cellularity performed on renal biopsy slides from these six patients and from eight ANCA-negative patients with IgA nephropathy and crescents in greater than 50% of glomeruli showed significantly greater hypercellularity in the ANCA-negative cases. Three of five ANCA-positive patients for whom follow-up clinical data were available showed improved renal function after treatment with cyclophosphamide and corticosteroids and have not developed end-stage renal disease 17, 20, and 25 months postbiopsy. The remaining two patients were dialysis dependent at the time of biopsy and have remained so despite treatment with cyclophosphamide and corticosteroids. The findings suggest an overlap syndrome of ANCA-associated crescentic GN and IgA nephropathy that resembles the former both histologically and in its potential to respond to aggressive therapy if detected relatively early in its course.
抗中性粒细胞胞浆自身抗体（ANCA）通常与一种坏死性新月体性肾小球肾炎（GN）相关，这种肾炎为少免疫性，通过免疫荧光（IF）或电子显微镜（EM）检测，肾小球免疫复合物沉积很少或无。免疫球蛋白A（IgA）肾病也可表现为新月体性GN，但其特征为含有IgA的系膜免疫复合物沉积，当采用酶免疫测定法检测这些抗体时，很少与髓过氧化物酶（MPO）或蛋白酶3（PR3）特异性ANCA相关。本报告描述了6例严重新月体性GN患者，IF显示系膜有IgA沉积，EM显示系膜有电子致密沉积物，这些患者ANCA血清学检测结果为阳性（4例抗PR3；1例抗MPO；1例抗PR3和抗MPO）。患者表现为急性或进行性肾功能不全、血尿、蛋白尿（2例为肾病范围）和高血压。3例患者有系统性血管炎证据：2例在初次就诊时出现，1例在临床病程后期出现。肾活检标本显示所有病例中超过50%的肾小球有新月体形成，但仅见轻度、局灶性和节段性系膜及毛细血管内细胞增多，这更典型地见于ANCA相关新月体性GN，而非无相关ANCA的新月体性IgA肾病。对这6例患者以及8例肾小球新月体形成超过50%的ANCA阴性IgA肾病患者的肾活检玻片进行系膜和毛细血管内细胞增多的半定量分析，结果显示ANCA阴性病例的细胞增多明显更严重。5例有随访临床数据的ANCA阳性患者中，3例在接受环磷酰胺和糖皮质激素治疗后肾功能改善，活检后17、20和25个月未发展为终末期肾病。其余2例患者在活检时依赖透析，尽管接受了环磷酰胺和糖皮质激素治疗，仍维持透析状态。这些发现提示ANCA相关新月体性GN和IgA肾病存在重叠综合征，在组织学上以及如果在病程相对早期发现时对积极治疗的反应潜力方面均类似于前者。
