Allen A C, Bailey E M, Brenchley P E, Buck K S, Barratt J, Feehally J
Department of Nephrology, Leicester General Hospital, Leicester, England, United Kingdom.
Kidney Int. 2001 Sep;60(3):969-73. doi: 10.1046/j.1523-1755.2001.060003969.x.
In IgA nephropathy (IgAN), circulating IgA1 molecules display an abnormal pattern of O-glycosylation. This abnormality may potentially contribute to mesangial IgA1 deposition, but this is unproven because the O-glycosylation of mesangial IgA1 has not been analyzed.
IgA1 was eluted from glomeruli isolated from the kidneys of three IgAN patients obtained after nephrectomy or at postmortem. Serum from these patients, other patients with IgAN, and controls was subjected to the same treatment as the glomerular eluates. The O-glycosylation of eluted and serum IgA1 was measured by lectin binding using an enzyme-linked immunosorbent assay-based system.
In all three cases, the lectin binding of IgA1 eluted from the glomeruli of IgAN patients was markedly higher than that of the serum IgA1 of the same individual, and also all but one of a series of serum IgA1 samples from other patients and controls.
The higher lectin binding of glomerular compared with serum IgA1 suggests that O-glycosylated IgA1 molecules abnormally and selectively deposit in the kidney. These results provide the first evidence that mesangial IgA1 is abnormally O-glycosylated, and support a direct role for abnormal IgA1 O-glycosylation in the mechanism of mesangial IgA deposition in IgAN.
在IgA肾病（IgAN）中，循环中的IgA1分子呈现出异常的O-糖基化模式。这种异常可能潜在地导致系膜IgA1沉积，但这尚未得到证实，因为系膜IgA1的O-糖基化尚未被分析。
从三名IgAN患者肾切除术后或尸检后获得的肾脏中分离出肾小球，从中洗脱IgA1。这些患者、其他IgAN患者以及对照组的血清接受与肾小球洗脱物相同的处理。使用基于酶联免疫吸附测定的系统，通过凝集素结合来测量洗脱的和血清中的IgA1的O-糖基化。
在所有三个病例中，从IgAN患者肾小球洗脱的IgA1的凝集素结合明显高于同一患者的血清IgA1，也高于其他患者和对照组的一系列血清IgA1样本中除一个之外的所有样本。
与血清IgA1相比，肾小球的凝集素结合更高，这表明O-糖基化的IgA1分子异常且选择性地沉积在肾脏中。这些结果首次证明系膜IgA1存在异常的O-糖基化，并支持异常的IgA1 O-糖基化在IgAN系膜IgA沉积机制中起直接作用。
