Leucocyte beta 1,3 galactosyltransferase activity in IgA nephropathy
Leucocyte beta 1,3 galactosyltransferase activity in IgA nephropathy
复制标题
DOI：
10.1093/ndt/12.4.701
复制
发表时间：
1997-04-01
影响因子：
6.1
通讯作者：
Feehally, J
中科院分区：
文献类型：
--
作者：
Allen, AC;Topham, PS;Feehally, J
背景。最近描述了 IgAN 中 IgA1 铰链区 O 连接聚糖的半乳糖基化减少。为了研究导致这种异常的潜在缺陷，我们测量了 β1,3 半乳糖基转移酶的活性，该酶负责 O-连接糖的半乳糖基化。方法，从正常 IgA1 的去半乳糖基化铰链区片段制备半乳糖受体底物，并与来自患有糖尿病的患者的 T 细胞、B 细胞和单核细胞裂解物一起孵育。 IgAN 和受体再半乳糖基化的对照。然后用生物素化的蚕豆凝集素 (VV) 测量受体半乳糖基化的程度，该凝集素对非半乳糖基化部分具有特异性。还测量了来自同一受试者的血清 IgA 的凝集素结合。结果。 IgAN 和对照之间的 T 细胞和单核细胞 β 1,3 半乳糖基转移酶活性没有差异，但 IgAN 中的 B 细胞裂解物显示比对照显着降低的 β 1,3 半乳糖基转移酶活性（6.2 +/- 0.71 与 9.5 +/- 1.03 AU/μg，P = 0.018）。此外，B 细胞 β 1,3 半乳糖基转移酶活性与 IgAN 中血清 IgA 的 VV 凝集素结合呈负相关（r = -0.87，P = 0.002），但与对照组无关。 结论：这些数据表明，IgAN 中 IgA1 O-半乳糖基化的改变是由于 B 细胞限制性 β 1,3 半乳糖基转移酶活性降低所致。这种酶缺陷可能是 IgAN 的基本致病异常。
Background. Reduced galactosylation of the O-linked glycans of the IgA1 hinge region in IgAN has recently been described. To investigate the underlying defect resulting in this abnormality, we have measured the activity of beta 1,3 galactosyltransferase, the enzyme responsible for galactosylation of O-linked sugars.Methods, A galactose-acceptor substrate was prepared from degalactosylated hinge region fragments of normal IgA1, and incubated with the T cell, B cell, and monocyte lysates from patients with IgAN and controls for acceptor regalactosylation. The extent of acceptor galactosylation was then measured with biotinylated Vicia villosa lectin (VV), which is specific for ungalactosylated moieties. Lectin binding of serum IgA from the same subjects was also measured.Results. T cell and monocyte beta 1,3 galactosyltransferase activities did not differ between IgAN and control, but B cell lysates in IgAN showed significantly lower beta 1,3 galactosyltransferase activity than control (6.2 +/- 0.71 vs. 9.5 +/- 1.03 AU/mu g, P = 0.018). Furthermore, B cell beta 1,3 galactosyltransferase activity showed a negative correlation (r = -0.87, P = 0.002) with VV lectin binding of serum IgA in IgAN, but not controls.Conclusions, These data indicate that altered IgA1 O-galactosylation in IgAN results from a B cell-restricted reduction of beta 1,3 galactosyltransferase activity. This enzyme defect may be a fundamental pathogenic abnormality in IgAN.