Does the renal expression of Toll-like receptors play a role in patients with IgA nephropathy?

Does the renal expression of Toll-like receptors play a role in patients with IgA nephropathy?
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DOI:
10.1007/s40620-019-00640-z
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发表时间:
2020-04-01
影响因子:
3.4
通讯作者:
Maixnerova, Dita
Maixnerova, Dita
中科院分区:
医学3区
文献类型:
--
作者:
Ciferska, Hana;Honsova, Eva;Maixnerova, Dita

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伊加肾病(IgAN)的发病特征是含IgA的免疫复合物在肾小球沉积,常伴有咽旁血尿。由Toll样受体(TLR)介导的先天免疫应答可能在IgAN的发病和/或进展中起作用。在这里,我们评估了TLR 4,7,8和9的表达与IgAN患者的肾活检标本,不同程度的蛋白尿和eGFR,与正常肾脏和疾病对照组织(ANCA相关血管炎)相比。肾活检标本来自34例IgAN和7例ANCA相关血管炎患者。此外,我们使用了15个健康部分的肾组织标本,从肾脏切除后的癌症作为对照标本。TLR 4,7,8和9的表达进行了评估,采用免疫组化染色的石蜡包埋的肾活检组织标本的特异性抗体,并通过光学显微镜进行半定量评价。使用线性判别分析(LDA)来测试TLR 4、7、8和9的肾内染色是否将IgAN患者与对照区分开或与eGFR和/或蛋白尿相关。使用基于肌酐的公式计算eGFR。此外,IgAN患者的活检组织根据牛津分类进行评分。LDA显示,与正常肾组织相比,IgAN患者的标本中TLR 4、7、8和9的染色更强烈。肾内TLRs染色的强度区分四组具有不同eGFR和蛋白尿以及MEST评分的IgAN患者。
The onset of IgA nephropathy (IgAN), characterized by glomerular deposition of IgA-containing immune complexes, is often associated with synpharyngitic hematuria. Innate immune responses mediated by Toll-like receptors (TLR) may play a role in IgAN onset and/or progression. Here, we assessed the expression of TLR 4, 7, 8, and 9 in renal-biopsy specimens from patients with IgAN, with different degree of proteinuria and eGFR, compared with normal-kidney and disease-control tissues (ANCA-associated vasculitis). Renal-biopsy specimens from 34 patients with IgAN and 7 patients with ANCA-associated vasculitis were used. In addition, we used 15 healthy portions of renal-tissue specimens from kidneys after nephrectomy for cancer as control specimens. Expression of TLR 4, 7, 8, and 9 was assessed using immunohistochemical staining of paraffin-embedded renal-biopsy tissue specimens with specific antibodies and evaluated semiquantitatively by light microscopy. Linear discriminant analysis (LDA) was used to test whether intrarenal staining of TLR 4, 7, 8, and 9 distinguished patients with IgAN from controls or correlated with eGFR and/or proteinuria. eGFR was calculated using the creatinine-based formula. Moreover, the biopsies from patients with IgAN were scored according to the Oxford Classification. LDA showed that staining for TLR 4, 7, 8, and 9 was more intense in specimens from IgAN patients compared to normal kidney tissues. The intensity of intrarenal staining of TLRs discriminated four groups of IgAN patients with different eGFR and proteinuria and MEST scoring.