Smeets Bart, Stucker Fabien, Wetzels Jack, Brocheriou Isabelle, Ronco Pierre, Gröne Hermann-Josef, D'Agati Vivette, Fogo Agnes B, van Kuppevelt Toin H, Fischer Hans-Peter, Boor Peter, Floege Jürgen, Ostendorf Tammo, Moeller Marcus J
Division of Nephrology and Clinical Immunology, Department of Internal Medicine II, RWTH Aachen University Hospital, Aachen, Germany.
Department of Pathology, INSERM U702, Hôpital Tenon, Paris, France; Nephrology Service, University Hospitals of Geneva (HUG), Geneva, Switzerland.
Am J Pathol. 2014 Dec;184(12):3239-48. doi: 10.1016/j.ajpath.2014.08.007. Epub 2014 Oct 7.
In rodents, parietal epithelial cells (PECs) migrating onto the glomerular tuft participate in the formation of focal segmental glomerulosclerosis (FSGS) lesions. We investigated whether immunohistologic detection of PEC markers in the initial biopsies of human patients with first manifestation of idiopathic nephrotic syndrome with no immune complexes can improve the sensitivity to detect sclerotic lesions compared with standard methods. Ninety-five renal biopsies were stained for claudin-1 (PEC marker), CD44 (activated PECs), and LKIV69 (PEC matrix); 38 had been diagnosed as early primary FSGS and 57 as minimal change disease. PEC markers were detected on the tuft in 87% of the biopsies of patients diagnosed as primary FSGS. PEC markers were detected in FSGS lesions from the earliest stages of disease. In minimal change disease, no PEC activation was observed by immunohistology. However, in 25% of biopsies originally diagnosed as minimal change disease the presence of small lesions indicative of a sclerosing process were detected, which were undetectable on standard periodic acid-Schiff staining, even though only a single histologic section for each PEC marker was evaluated. Staining for LKIV69 detected lesions with the highest sensitivity. Two novel PEC markers A-kinase anchor protein 12 and annexin A3 exhibited similar sensitivity. In summary, detection of PECs on the glomerular tuft by immunostaining improves the differentiation between minimal change disease and primary FSGS and may serve to guide clinical decision making.
在啮齿动物中，迁移到肾小球上的壁层上皮细胞（PEC）参与局灶节段性肾小球硬化（FSGS）病变的形成。我们研究了在首次表现为无免疫复合物的特发性肾病综合征的人类患者的初始活检中，通过免疫组织化学检测PEC标志物，与标准方法相比，是否能提高检测硬化性病变的敏感性。对95份肾活检组织进行了紧密连接蛋白-1（PEC标志物）、CD44（活化的PEC）和LKIV69（PEC基质）染色；其中38例被诊断为早期原发性FSGS，57例为微小病变肾病。在诊断为原发性FSGS的患者的87%的活检组织中，在肾小球上检测到了PEC标志物。在疾病的最早阶段，FSGS病变中就检测到了PEC标志物。在微小病变肾病中，免疫组织学未观察到PEC激活。然而，在最初诊断为微小病变肾病的25%的活检组织中，检测到了提示硬化过程的小病变，即使对每个PEC标志物仅评估了一个组织学切片，这些病变在标准高碘酸-希夫染色中也无法检测到。对LKIV69染色检测病变的敏感性最高。两种新型PEC标志物A激酶锚定蛋白12和膜联蛋白A3表现出相似的敏感性。总之，通过免疫染色检测肾小球上的PEC可改善微小病变肾病和原发性FSGS之间的鉴别，并可能有助于指导临床决策。
