血清抗核抗体阳性的不典型膜性肾病与狼疮膜性肾病及特发性膜性肾病的临床病理比较

目的 探讨血清抗核抗体（ANA）阳性的不典型膜性肾病（AMN）与狼疮膜性肾病（LMN）、特发性膜性肾病（IMN）的关系，寻找对诊断LMN具有较高预测价值的临床和病理学指标。 方法 2003年1月至2006年12月期间在北京协和医院住院并行肾活检，临床、病理资料保存完整的患者为对象。分组：AMN组（n = 28）：血清ANA滴度≥1∶80，少于4条美国风湿病学会（ARA）修订的系统性红斑狼疮分类标准，病理呈肾小球基底膜病变伴系膜增生和（或）免疫荧光C1q阳性；IMN组（n = 100）；LMN组（n = 45）。回顾性分析各组病例的临床表现、病理学特点。应用免疫组化法，对各组部分病例肾活检组织行IgG亚型染色，半定量分析染色强度。对各组部分病例肾活检组织行免疫荧光双染色（IgG-TRITC，C3-FITC），用激光扫描共聚焦显微镜观察肾小球沉积的IgG和C3的空间分布。 结果 (1)AMN组起病年龄（38±17）岁，女∶男比为2.5∶1，介于LMN和IMN之间。3组起病年龄差异有统计学意义（P < 0.01），AMN组女∶男比高于IMN组（P = 0.017）。AMN组血液系统异常、血抗SSA抗体阳性百分比较高（21.4%、40.7%）。(2)AMN组系膜增生、系膜区及内皮下电子致密物出现的百分比高于IMN组（P < 0.01）。(3)AMN和LMN组肾小球IgG3沉积占优势的百分比分别为78.9%、73.9%；IMN组IgG4沉积占优势的百分比为61.1%，差异均有统计学意义（IMN组与AMN、LMN组比较, P < 0.01）。(4)IMN组常出现IgG和C3在上皮下的共沉积现象，而在AMN和LMN组中少见。(5)在鉴别LMN和IMN的指标中，敏感性较高的有肾小球IgG4不占优势（91.3%）；特异性较高的有内皮下电子致密物（100.0%）、血抗SSA抗体（95.5%）、肾小球IgG3占优势（94.4%）。 结论 AMN的临床表现与IMN类似，而各项病理学特点，尤其是肾小球IgG亚型沉积特点与LMN更为接近。它有可能是狼疮肾炎中较为隐匿的一个亚型。

Clinicopathological comparison among atypical membranous nephropathy with serum antinuclear antibody positivity, lupus membranous nephropathy and idiopathic membranous nephropathy

Objectives To study the relationship of atypical membranous nephropathy (AMN) with idiopathic membranous nephropathy (IMN) and lupus membranous nephropathy (LMN), and to explore the predictive clinical and pathological features for LMN diagnosis. Methods The patients undergone renal biopsy in PUMCH between 2003 and 2006 were selected, and were divided into group AMN (n=28), IMN (n=100) and LMN (n=45). Clinical manifestations and pathological features were compared among three groups retrospectively. The intensity of glomerular IgG subclasses was analyzed by immunohistoehemical staining among three groups semi- quantitatively. The spatial arrangement of IgG and C3 deposits was investigated by immunofluorescenee double staining among three groups by eonfocal laser scanning microscopy. Results (1) The onset age of AMN was (38±17) years and female/male ratio(F/M) was 2.5:1 in group LMN and IMN. The onset age was significantly different among three groups (P<0.01), and F/M ratio was significantly different between AMN and IMN (P=0.017). (2) The incidence of most extra-renal manifestations was less than 20% in AMN except for hematological disorder (21.4%) and serum anti-SSA antibody positivity(40.7%). (3) The incidence of subendothelial electron densedeposits in either LMN or AMN was significantly higher than that in IMN (P<0.01). (4) The percentage of IgG3 predominance in AMN and LMN giomeruli was 78.9% and 73.9%, respectively, while the percentage of IgC,-4 predominance in IMN was 61.1%. The difference was significant(IMN vs AMN and LMN, P<0.01). (5) IMN had an overlapping distribution of IgG and C3 in subepithelial deposition, which was rarely found in AMN or LMN. (6) Among the indexes differentiating LMN and IMN, the high sensitive one was non-IgC,4 predominance in glomeruli (91.3%), while the high specific ones included subendothelial electron dense deposits (100.0%), serum anti-SSA antibody (95.5%), glomendar IgG3 predominance (94.4%). Conclusions AMN with serum ANA positivity is similar to LMN in respect to pathological features and glomerular IgG subclasses, although it has few extra-renal clinical manifestations. It may represent a latent subgroup of lupus nephritis.