Liu Ning, Mori Noriko, Iehara Noriyuki, Uemura Kazuhide, Fukastu Atsushi, Kita Toru, Matsuda Michio, Ono Takahiko
Division of Molecular Medicine, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Clin Exp Nephrol. 2007 Mar;11(1):71-6. doi: 10.1007/s10157-006-0457-0. Epub 2007 Mar 28.
Fibrin monomer and its derivatives in blood are found in an early stage of thrombosis. When they are produced in blood, they form complexes with fibrinogen, and they exist as soluble complexes named soluble fibrin (SF). As final insoluble products, cross-linked fibrin (XFb) is often observed in mesangial areas in active types of human glomerulonephritis. To clarify the mechanisms of mesangial SF production and its relationship to XFb deposition in IgA nephropathy (IgAN), an immunohistochemical study was conducted.
Nineteen patients with IgAN were studied. XFb was detected in renal biopsy specimens using anti-d-dimer antibody combined with plasmin exposure. SF was detected with a monoclonal antibody (IF-43), and factor V was detected with a specific rabbit antibody. The relationships of SF staining to the disease activity index, XFb deposition, and factor V staining was evaluated.
XFb, factor V, and SF were observed in the mesangium in 14, 11, and 8, respectively, of a total of 19 specimens. SF had frequent staining in the proliferating areas, showing a significant relationship to XFb or factor V (P < 0.05). Furthermore, XFb, factor V, and SF depositions were markedly correlated with disease activity (P < 0.001 in each case).
These findings suggest that SF is formed in the mesangial area in active IgA nephropathy accompanied by mesangial proliferation, in particular, in its early stage.
血液中的纤维蛋白单体及其衍生物在血栓形成的早期阶段即可被发现。当它们在血液中产生时,会与纤维蛋白原形成复合物,并以名为可溶性纤维蛋白(SF)的可溶性复合物形式存在。作为最终的不溶性产物,交联纤维蛋白(XFb)在人类活动性肾小球肾炎的系膜区中经常可见。为了阐明IgA肾病(IgAN)中系膜区SF产生的机制及其与XFb沉积的关系,我们进行了一项免疫组织化学研究。
对19例IgAN患者进行了研究。使用抗d - 二聚体抗体结合纤溶酶暴露检测肾活检标本中的XFb。用单克隆抗体(IF - 43)检测SF,用特异性兔抗体检测因子V。评估了SF染色与疾病活动指数、XFb沉积和因子V染色之间的关系。
在总共19个标本中,分别有14个、11个和8个标本在系膜区观察到XFb、因子V和SF。SF在增殖区域频繁染色,与XFb或因子V有显著相关性(P < 0.05)。此外,XFb、因子V和SF沉积与疾病活动显著相关(每种情况P < 0.001)。
这些发现表明,在伴有系膜增殖的活动性IgA肾病中,尤其是在其早期阶段,系膜区会形成SF。