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糖基化基因在 IgA 肾病伴蛋白尿和肾功能不全的扁桃体 B 淋巴细胞中的差异表达。

Differential expression of glycogenes in tonsillar B lymphocytes in association with proteinuria and renal dysfunction in IgA nephropathy.

机构信息

Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.

出版信息

Clin Immunol. 2010 Sep;136(3):447-55. doi: 10.1016/j.clim.2010.05.009. Epub 2010 Jun 11.

Abstract

Aberrant O-glycosylation of serum and tonsillar IgA1 is one of the main pathogeneses of IgA nephropathy (IgAN). However, the synthesis of underglycosylated IgA1 in tonsils has not yet been characterized. This study examined tonsillar B lymphocytes of IgAN (n=34) using tonsils derived from patients with chronic tonsillitis (n=24) and sleep apnea syndrome (n=14) as a control. Gene expression of beta1,3-galactosyltransferase (beta3GalT), and the core 1 beta3GalT-specific molecular chaperone, Cosmc, UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyl-transferase 2, were significantly decreased in tonsillar CD19-positive B lymphocytes from IgAN patients compared to control tonsillar tissues as determined by real-time RT-PCR. Tonsillar B cell beta3GalT gene expression significantly correlated with estimated GFR and negatively correlated with proteinuria and histological injury score. Western blotting showed the protein expression of beta3GalT in the tonsils to significantly decrease in IgAN in comparison to the controls. These data suggest the downregulation of beta3GalT in tonsillar B lymphocytes to be closely associated with the clinical characteristics of IgAN.

摘要

血清和扁桃体 IgA1 的异常糖基化是 IgA 肾病 (IgAN) 的主要发病机制之一。然而,扁桃体中未糖基化 IgA1 的合成尚未得到表征。本研究使用源自慢性扁桃体炎(n=24)和睡眠呼吸暂停综合征(n=14)患者的扁桃体作为对照,检查了 IgAN 患者的扁桃体 B 淋巴细胞(n=34)。通过实时 RT-PCR 测定,与对照扁桃体组织相比,IgAN 患者扁桃体 CD19 阳性 B 淋巴细胞中的β1,3-半乳糖基转移酶(β3GalT)和核心 1β3GalT 特异性分子伴侣 Cosmc、UDP-N-乙酰-α-D-半乳糖胺:多肽 N-乙酰半乳糖胺基转移酶 2 的基因表达显著降低。扁桃体 B 细胞β3GalT 基因表达与估计的肾小球滤过率显著相关,与蛋白尿和组织学损伤评分呈负相关。Western blot 显示,与对照组相比,IgAN 患者扁桃体中的β3GalT 蛋白表达显著降低。这些数据表明,扁桃体 B 淋巴细胞中β3GalT 的下调与 IgAN 的临床特征密切相关。

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