Hisano S, Matsushita M, Fujita T, Endo Y, Takebayashi S
Second Department of Pathology, Fukuoka University, School of Medicine, Fukuoka, Japan.
Am J Kidney Dis. 2001 Nov;38(5):1082-8. doi: 10.1053/ajkd.2001.28611.
Three pathways are recognized in complement activation. The aim of our study is to elucidate immunohistologically which complement pathway is associated with complement activation in immunoglobulin A (IgA) glomerulonephritis (GN) and which IgA subclass is related to complement activation. Immunohistological staining was performed on renal biopsy specimens obtained from 36 patients with IgA GN, 10 patients with systemic lupus erythematosus (SLE), and 16 patients with other GNs using polyclonal antibodies of IgG, IgA, IgM, C1q, C3c, and C4 and monoclonal antibodies of IgA1, IgA2, mannose-binding lectin (MBL), and MBL-associated serine protease-1 (MASP-1). Mesangial deposits of both IgA1 and IgA2 were found in 19 of 36 patients with IgA GN. Mesangial deposits of C3c, C4, MBL, and MASP-1 also were detected in these 19 patients, and IgA2, MBL, and MASP-1 deposits were colocalized in the mesangium in these patients. The remaining 17 patients showed mesangial deposits of IgA1 alone. Twelve of these 17 patients showed mesangial deposits of C3c without C4, MBL, or MASP-1. No deposition of C1q was evident in patients with IgA GN. Three of 10 patients with SLE showed glomerular deposition of MBL and MASP-1 without glomerular deposition of IgA2. None of the patients with other GNs showed glomerular deposition of IgA1, IgA2, MBL, or MASP-1. There was no correlation in clinical or pathological indicators between IgA2-positive and IgA2-negative patients with IgA GN. In conclusion, alternative pathway-involved complement activation is associated with mesangial deposits of IgA1 alone in patients with IgA GN. In those with mesangial deposits of both IgA1 and IgA2, both the alternative and lectin pathways are involved in complement activation. We first report that mesangial deposits of IgA2 may activate the lectin pathway in patients with IgA GN.
补体激活存在三条途径。我们研究的目的是通过免疫组织学方法阐明在免疫球蛋白A（IgA）肾小球肾炎（GN）中，哪条补体途径与补体激活相关，以及哪种IgA亚类与补体激活有关。使用IgG、IgA、IgM、C1q、C3c和C4的多克隆抗体以及IgA1、IgA2、甘露糖结合凝集素（MBL）和MBL相关丝氨酸蛋白酶-1（MASP-1）的单克隆抗体，对36例IgA GN患者、10例系统性红斑狼疮（SLE）患者和16例其他GN患者的肾活检标本进行免疫组织学染色。在36例IgA GN患者中的19例发现了IgA1和IgA2的系膜沉积。在这19例患者中也检测到了C3c、C4、MBL和MASP-1的系膜沉积，并且在这些患者中IgA2、MBL和MASP-1沉积在系膜中共定位。其余17例患者仅显示IgA1的系膜沉积。这17例患者中的12例显示C3c的系膜沉积，而无C4、MBL或MASP-1沉积。IgA GN患者中未发现C1q沉积。10例SLE患者中有3例显示MBL和MASP-1的肾小球沉积，但无IgA2的肾小球沉积。其他GN患者均未显示IgA1、IgA2、MBL或MASP-1的肾小球沉积。IgA GN的IgA2阳性和IgA2阴性患者在临床或病理指标上无相关性。总之，在IgA GN患者中，替代途径参与的补体激活与仅IgA1的系膜沉积相关。在同时有IgA1和IgA2系膜沉积的患者中，替代途径和凝集素途径均参与补体激活。我们首次报道IgA2的系膜沉积可能在IgA GN患者中激活凝集素途径。
