Mesangial IgA1 in IgA nephropathy exhibits aberrant O-glycosylation: Observations in three patients
Mesangial IgA1 in IgA nephropathy exhibits aberrant O-glycosylation: Observations in three patients
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DOI：
10.1046/j.1523-1755.2001.060003969.x
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发表时间：
2001-09-01
影响因子：
19.6
通讯作者：
Feehally, J
中科院分区：
文献类型：
--
作者：
Allen, AC;Bailey, EM;Feehally, J
背景。在 IgA 肾病 (IgAN) 中，循环 IgA1 分子表现出异常的 O-糖基化模式。这种异常可能可能导致系膜 IgA1 沉积，但这尚未得到证实，因为尚未分析系膜 IgA1 的 O-糖基化。方法。 IgA1 从肾切除术后或死后获得的三名 IgAN 患者肾脏中分离的肾小球中洗脱。来自这些患者、其他 IgAN 患者和对照的血清接受与肾小球洗脱液相同的处理。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 IgA1 和血清 IgA1 的 O-糖基化。结果。在所有三个病例中，从 IgAN 患者肾小球洗脱的 IgA1 的凝集素结合显着高于同一个体的血清 IgA1，以及来自其他患者和对照的一系列血清 IgA1 样本中的所有样本。结论。与血清 IgA1 相比，肾小球凝集素结合较高，表明 O-糖基化 IgA1 分子异常且选择性地沉积在肾脏中。这些结果提供了系膜 IgA1 异常 O-糖基化的第一个证据，并支持异常 IgA1 O-糖基化在 IgAN 系膜 IgA 沉积机制中的直接作用。
Background. 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.Methods. 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.Results. 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.Conclusions. 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.