肾小球毛细血管内增生伴巨噬细胞浸润的IgA肾病

IgA nephropathy with endocapillary hypercellularity and macrophage infiltration

目的:阐述IgA肾病伴毛细血管内增生(IgAN-E)及肾小球大量巨噬细胞浸润患者的临床病理特征及预后,并探究其发病机制。方法:取62例IgAN-E患者的肾小球CD68^+细胞数的第95百分位数作为大量巨噬细胞浸润的阈值,超过此阈值的IgAN-E患者作为研究组,反之则作为对照组。回顾性分析两组患者的临床病理及随访资料。以CD68、诱生型一氧化氮合酶(iNOS)、CD163、CD3、CD20作为细胞标记物行免疫组化染色单克隆;KM55抗体可特异地结合异常糖基化IgA1(Gd-IgA1),将之与IgA行免疫荧光套染。结果:62例IgAN-E患者肾小球CD68^+细胞中位数为4.2(2.3～6.1)个/肾小球,其第95百分位数为14个/肾小球。共纳入38例患者为研究组,男性17例、女性21例,肾活检时平均年龄36±17岁。与对照组患者相比,研究组患者肾活检时的蛋白尿、胆固醇、三酰甘油更高,白蛋白更低;E病变更重,肾小球硬化和肾小管萎缩间质纤维化程度更轻(所有P<0.05);随访时免疫抑制剂使用率更高和肾脏预后更差(P=0.002)。研究组肾小球浸润的炎细胞以CD68^+和CD163^+细胞为主,均与E%呈正相关,与肾功能不相关。KM55与IgA免疫荧光显示两组患者肾小球沉积的IgA均为Gd-IgA1。结论:IgAN-E肾小球大量巨噬细胞浸润患者具有独特的临床病理特征,表现为临床病理改变活动性更高,肾脏预后更差。

Objective:To characterize the clinicopathological features and prognosis of IgA nephropathy patients with endocapillary hypercellularity(IgAN-E) and massive glomerular macrophage infiltration, to explore their pathogenesis. Methodology:The 95 th percentile of the glomerular CD68^+ cells counts from 62 IgAN-E cases was defined as the threshold for massive macrophage infiltration.Patients with biopsies that met the threshold were enrolled as the study group and patients that did not meet as the control group.Clinicopathological features and follow-up data were evaluated.Immunohistochemical staining was performed with the cell biomarker of CD68,iNOS,CD163,CD3 and CD20.Abnormal glycosylated IgA1(Gd-IgA1) was immunofluorescently stained with KM55,and overlapped with IgA. Results:The median number of glomerular CD68^+ cells in 62 IgAN-E patients was 4.2(2.3~6.1) cell/glomerulus,with 95 th percentile of 14 cell/glomerulus. A total of 38 patients were enrolled in the study group,including 17 males and 21 females;the mean age was 36±17 years. Compared with 59 control group,patients in the study group showed significantly higher proteinuria,cholesterol and triglyceride,lower albumin levels,increased E lesion but decreased glomerulosclerosis,tubular atrophy and interstitial fibrosis at biopsy(all P<0.05);higher percentage of immunosuppressants treatment and worse renal prognosis(P=0.002) during follow-up. The glomerular infiltrating inflammatory cells in the study group were mainly CD68^+ and CD163^+ cells,which both were positively correlated with E% but not with renal function. The co-localization of KM55 and IgA in the two groups confirmed that the IgA deposit in glomeruli was Gd-IgA1. Conclusion:IgAN-E with massive glomerular macrophage infiltration patients have distinctive clinicopathological features,showing a more active clinicopathological findings and worse renal prognosis.