Endo M, Ohi H, Satomura A, Hidaka M, Ohsawa I, Fujita T, Kanmatsuse K, Matsushita M, Fujita T
The 2nd Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Clin Nephrol. 2001 Mar;55(3):185-91.
The lectin pathway, which is initiated by mannose-binding lectin (MBL) and MBL-associated serine protease (MASP), is one of the possible routes to activate the complement cascade in immunoglobulin A (IgA) nephropathy. The purpose of this study was to elucidate the regulatory mechanism of the pathway. Levels of complement activation products and regulatory proteins were measured in sera from 27 patients with IgA nephropathy, and generation of fluid-phase complement activation products in the presence of pooled normal human serum was quantified to evaluate activation in vitro. Although there were no significant differences in the serum levels and in vitro activation between the MBL-MASP positive (n = 14) and negative (n = 13) groups, there were positive correlations between complement activation products (Bb fragment and C4d fragment) and regulatory proteins (factor H, C4-binding protein, and C1 inhibitor) in the MBL-MASP-positive group. Furthermore, immunohistochemical studies demonstrated glomerular deposition of the regulatory protein (C4-binding protein, alpha2-macroglobulin, and factor H) in all patients in the MBL-MASP-positive group. These findings suggest that the regulatory proteins control in situ complement activation via the lectin pathway immediately, and continuous activation due to inadequate control will lead to the advanced glomerular injury.
由甘露糖结合凝集素（MBL）和MBL相关丝氨酸蛋白酶（MASP）启动的凝集素途径是免疫球蛋白A（IgA）肾病中激活补体级联反应的可能途径之一。本研究的目的是阐明该途径的调控机制。检测了27例IgA肾病患者血清中补体激活产物和调节蛋白的水平，并对在正常人混合血清存在下液相补体激活产物的生成进行了定量，以评估体外激活情况。虽然MBL-MASP阳性组（n = 14）和阴性组（n = 13）的血清水平和体外激活无显著差异，但MBL-MASP阳性组中补体激活产物（Bb片段和C4d片段）与调节蛋白（H因子、C4结合蛋白和C1抑制物）之间存在正相关。此外，免疫组织化学研究显示，MBL-MASP阳性组所有患者的调节蛋白（C4结合蛋白、α2巨球蛋白和H因子）均有肾小球沉积。这些发现表明，调节蛋白可立即通过凝集素途径原位控制补体激活，而由于控制不足导致的持续激活将导致晚期肾小球损伤。
