Endo M, Ohi H, Ohsawa I, Fujita T, Matsushita M, Fujita T
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Nephrol Dial Transplant. 1998 Aug;13(8):1984-90. doi: 10.1093/ndt/13.8.1984.
IgA nephropathy (IgA-N) is considered the most common glomerular disease in the world and leads to renal failure in a substantial number of patients. Although many studies have looked at the pathogenesis of the disease, many points need to be clarified, including the mechanism of complement activation. Recent studies have shown that mannose-binding lectin (MBL or mannose binding protein, MBP) initiates activation of the complement cascade (lectin pathway) utilizing two types of MBP-associated serine protease, namely MASP-1 and MASP-2. The present study was undertaken to elucidate whether the lectin pathway was involved in the pathogenic mechanism of IgA-N.
Forty-five renal biopsy cases with IgA-N, 35 cases with other forms of glomerulonephritis (GN), and normal kidney tissues were collected and an immunohistochemical study was performed using monoclonal antibodies against MBL and MASP-1. Furthermore, clinicopathological and serological features were also analysed in the patients with IgA-N.
Glomerular deposition of MBL, which was accompanied by MASP-1, was detected in 11 of 45 (24.4%) cases with IgA-N, while it was detected in only one case with other forms of GN. The deposited MBL/MASP-1 was observed to associate with C3b/C3c and C5b-9 but not with IgG, IgM, C1q, C4c, or properdin. Compared with MBL/MASP-1 negative cases with IgA-N, the positive cases with IgA-N were young and the renal biopsies had been performed at an early stage of the disease. No significant correlation was found between glomerular deposition of MBL/MASP-1 and proteinuria, haematuria, creatinine clearance, and serum levels of IgA, C3, or C4 at the time of renal biopsy. There were also no significant differences between MBL/MASP-1 positive cases and negative cases in the plasma levels of circulating immune complexes or soluble C5b-9.
The lectin pathway of complement activation, which is initiated by the MBL/MASPs complex, evidently contributes to the development of glomerular injury in a significant number of cases with IgA-N. In addition, these findings will add insight to the pathogenesis of IgA-N, including its relation to infection, since MBL plays a crucial role in the host defense against various pathogens.
IgA 肾病（IgA-N）被认为是全球最常见的肾小球疾病，会导致大量患者出现肾衰竭。尽管许多研究探讨了该疾病的发病机制，但仍有许多问题需要阐明，包括补体激活的机制。最近的研究表明，甘露糖结合凝集素（MBL 或甘露糖结合蛋白，MBP）利用两种与 MBP 相关的丝氨酸蛋白酶（即 MASP-1 和 MASP-2）启动补体级联反应（凝集素途径）。本研究旨在阐明凝集素途径是否参与 IgA-N 的致病机制。
收集 45 例 IgA-N 肾活检病例、35 例其他形式的肾小球肾炎（GN）病例及正常肾组织，使用抗 MBL 和 MASP-1 的单克隆抗体进行免疫组织化学研究。此外，还对 IgA-N 患者的临床病理和血清学特征进行了分析。
在 45 例 IgA-N 病例中的 11 例（24.4%）检测到伴有 MASP-1 的 MBL 肾小球沉积，而在其他形式的 GN 中仅 1 例检测到。观察到沉积的 MBL/MASP-1 与 C3b/C3c 和 C5b-9 相关，但与 IgG、IgM、C1q、C4c 或备解素无关。与 IgA-N 的 MBL/MASP-1 阴性病例相比，阳性病例较为年轻，且肾活检是在疾病早期进行的。在肾活检时，MBL/MASP-1 的肾小球沉积与蛋白尿、血尿、肌酐清除率以及 IgA、C3 或 C4 的血清水平之间未发现显著相关性。MBL/MASP-1 阳性病例和阴性病例在循环免疫复合物或可溶性 C5b-9 的血浆水平上也没有显著差异。
由 MBL/MASPs 复合物启动的补体激活凝集素途径显然在大量 IgA-N 病例的肾小球损伤发展中起作用。此外，这些发现将为 IgA-N 的发病机制提供新的见解，包括其与感染的关系，因为 MBL 在宿主抵御各种病原体方面起着关键作用。
