Tonsillar TLR9 expression and efficacy of tonsillectomy with steroid pulse therapy in IgA nephropathy patients
Tonsillar TLR9 expression and efficacy of tonsillectomy with steroid pulse therapy in IgA nephropathy patients
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DOI：
10.1093/ndt/gfr403
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发表时间：
2012-03-01
影响因子：
6.1
通讯作者：
Tomino, Yasuhiko
中科院分区：
文献类型：
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作者：
Sato, Daisuke;Suzuki, Yusuke;Tomino, Yasuhiko
背景伊加肾病（IgAN）患者在粘膜感染，特别是扁桃体炎后，常表现为肾损伤加重，伴有肉眼血尿。我们以前证明了粘膜的重要作用！Toll样受体9（TLR 9）在小鼠IgAN发病机制中的活化。此外，TLR 9的单核苷酸多态性（SNP）与人类IgAN的病理严重程度显著相关。在这项研究中，我们研究了IgAN患者扁桃体TLR 9信使RNA表达、TLR 9 SNP基因型与扁桃体切除术联合类固醇脉冲治疗（SPT）后临床结局之间的相关性。在IgAN（n = 49）和对照组（n = 15）中检测扁桃体TLR 9表达，这些患者接受了扁桃体切除术。观察扁桃体TLR 9表达水平、TLR 9 SNP基因型与SPT扁桃体切除术后临床预后的相关性。扁桃体TLR 9的高表达与23%的IgAN患者相似。这些患者比TLR 9低表达的患者表现出更强和更早的血尿和蛋白尿缓解。TLR 9基因rs352140位点TT基因型患者的肾功能损害较其他基因型患者严重。扁桃体切除术后血清伊加水平下降超过平均水平的患者（大Delta伊加）的蛋白尿累积缓解率高于这些水平下降较小的患者（小AlgA）。大Delta伊加患者CT/CC基因型占优势，扁桃体TLR 9表达显著高于小Delta伊加患者。在IgAN患者中，扁桃体TLR 9和TLR 9 SNP的表达水平与SPT扁桃体切除术的疗效密切相关。
Background. Patients with IgA nephropathy (IgAN) often show aggravation of renal injury with macroscopic hematuria after mucosal infections, especially tonsillitis. We previously demonstrated the important role of mucosa! Toll-like receptor 9 (TLR9) activation in the pathogenesis of murine IgAN. Moreover, a single nucleotide polymorphism (SNP) in TLR9 was significantly associated with pathological severity in human IgAN. In this study, we investigated correlations between tonsillar TLR9 messenger RNA expression, TLR9 SNP genotypes and clinical outcomes following tonsillectomy with steroid pulse therapy (SPT) in IgAN patients.Methods. Tonsillar TLR9 expression was examined in IgAN (n = 49) and control (n = 15) patients who had undergone tonsillectomy. The correlations between tonsillar TLR9 expression level, TLR9 SNP genotypes and clinical outcomes after tonsillectomy with SPT were examined.Results. High expression of tonsillar TLR9 was observed in similar to 23% of IgAN patients. These patients showed stronger and earlier remission of hematuria and proteinuria than those with low TLR9 expression. Patients with the TT genotype of TLR9 SNP (rs352140) had more severe renal damage than those with other genotypes. Patients whose serum IgA level decreased more than average after tonsillectomy (large Delta IgA) showed higher cumulative remission rates of proteinuria than patients with a smaller decrease in these levels (small AlgA). CT/CC genotypes were more dominant and tonsillar TLR9 expressions significantly higher in large Delta IgA patients than in small Delta IgA patients.Conclusion. In IgAN patients, expression levels of tonsillar TLR9 and TLR9 SNP were well correlated with the efficacy of tonsillectomy with SPT.