Department of Immunology, Landspitali University Hospital, Reykjavik, Iceland.
APMIS. 2013 Sep;121(9):890-7. doi: 10.1111/apm.12051. Epub 2013 Feb 11.
Defective glycosylation and immune complex (IC) formation may be of primary importance in immunoglobulin A nephropathy (IgAN) pathogenesis. The aim of this study was to determine whether defective IgA1 glycosylation might support renal deposition of IgA and disease activity. IgA was isolated from the serum of 44 IgAN patients and 46 controls and glycosylation analysed by ELISA using glycan-specific lectins. IgA was measured by immunodiffusion and immune complexes by ELISA. IgA subclasses in IC deposits in kidney glomeruli were identified by immunohistochemical methods. A significant increase in N-acetylgalactosamine (GalNAc) in terminal position (p = 0.02) observed in some of the IgAN patients, became more pronounced when sialic acid was removed from IgA1, indicating enhanced expression of α-2,6-sialyltransferase in patients compared with controls (p < 0.0001). Patients with defective galactosylation had lower serum IgA than other IgAN patients (p = 0.003). IgAN patients with both IgA1 and IgA2 glomerular deposits (21.7%) had increased GalNAc in terminal position (p = 0.003). Taken together, our results show that increased IgA glycosylation in IgAN associates with low levels of IgA, concomitant IgA1 and IgA2 glomerular deposits and poor clinical outcome.
糖基化和免疫复合物（IC）形成缺陷可能在 IgA 肾病（IgAN）发病机制中具有重要作用。本研究旨在确定 IgA1 糖基化缺陷是否支持 IgA 在肾脏中的沉积和疾病活动。从 44 例 IgAN 患者和 46 例对照者的血清中分离 IgA，并用糖基特异性凝集素通过 ELISA 分析糖基化。用免疫扩散法测定 IgA，用 ELISA 测定免疫复合物。通过免疫组织化学方法鉴定肾小球中 IC 沉积物中的 IgA 亚类。在一些 IgAN 患者中观察到末端 N-乙酰半乳糖胺（GalNAc）（p = 0.02）显著增加，当 IgA1 中的唾液酸被去除时，这种增加更为明显，表明与对照组相比，患者中 α-2,6-唾液酸转移酶的表达增强（p < 0.0001）。糖基化缺陷的患者血清 IgA 低于其他 IgAN 患者（p = 0.003）。具有 IgA1 和 IgA2 肾小球沉积物的 IgAN 患者（21.7%）具有末端 GalNAc 增加（p = 0.003）。综上所述，我们的结果表明，IgAN 中 IgA 的糖基化增加与 IgA 水平低、同时存在 IgA1 和 IgA2 肾小球沉积物以及临床预后不良有关。
