Institute of Rheumatology, 1st Faculty of Medicine, Charles University, 128 50, Prague, Czech Republic.
Department of Pathology, Institute of Clinical and Experimental Medicine, 140 21, Prague, Czech Republic.
J Nephrol. 2020 Apr;33(2):307-316. doi: 10.1007/s40620-019-00640-z. Epub 2019 Sep 5.
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.
IgA 肾病（IgAN）的发病特点是肾小球沉积含有 IgA 的免疫复合物，常伴有咽峡炎血尿。Toll 样受体（TLR）介导的固有免疫反应可能在 IgAN 的发病和/或进展中起作用。在此，我们评估了 TLR4、7、8 和 9 在 IgAN 患者肾活检标本中的表达情况，这些患者的蛋白尿和 eGFR 程度不同，与正常肾脏和疾病对照组织（抗中性粒细胞胞质抗体相关性血管炎）进行了比较。使用了 34 例 IgAN 患者和 7 例抗中性粒细胞胞质抗体相关性血管炎患者的肾活检标本，此外，我们还使用了 15 例因癌症行肾切除术的健康肾脏组织标本作为对照标本。使用针对 TLR4、7、8 和 9 的特异性抗体对石蜡包埋肾活检组织标本进行免疫组织化学染色，通过光学显微镜进行半定量评估。采用线性判别分析（LDA）检测 TLR4、7、8 和 9 的肾内染色是否能区分 IgAN 患者与对照组，以及是否与 eGFR 和/或蛋白尿相关。使用基于肌酐的公式计算 eGFR。此外，根据牛津分类对 IgAN 患者的活检进行评分。LDA 显示，与正常肾脏组织相比，IgAN 患者的肾组织 TLR4、7、8 和 9 的染色强度更高。TLRs 的肾内染色强度可区分不同 eGFR 和蛋白尿以及 MEST 评分的四组 IgAN 患者。
