Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, No 8, Xishiku Street, Xicheng District, Beijing, 100034, China.
Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.
J Transl Med. 2019 Jun 11;17(1):197. doi: 10.1186/s12967-019-1949-5.
Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are intracellular sensors of pathogens and molecules from damaged cells to regulate the inflammatory response in the innate immune system. Emerging evidences suggested a potential role of NLRs in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study aimed to investigate the expression of nucleotide-binding oligomerization domain containing protein 2 (NOD2), NOD-like receptor family pyrin domain containing 3 (NLRP3) and NOD-like receptor family CARD domain containing 5 (NLRC5) in kidneys of AAV patients, and further explored their associations with clinical and pathological parameters.
Thirty-four AAV patients in active stage were recruited. Their renal specimens were processed with immunohistochemistry to assess the expression of three NLRs, and with double immunofluorescence to detect NLRs on intrinsic and infiltrating cells. Analysis of gene expression was also adopted in cultured human podocytes. The associations between expression of NLRs and clinicopathological parameters were analyzed.
The expression of NOD2, NLRP3 and NLRC5 was significantly higher in kidneys from AAV patients than those from normal controls, minimal change disease or class IV lupus nephritis. These NLRs co-localized with podocytes and infiltrating inflammatory cells. The mean optical density of NOD2 in glomeruli was significantly higher in crescentic class than non-crescentic class, and correlated with levels of proteinuria and serum creatinine at renal biopsy. The mean optical density of NLRC5 in glomeruli was significantly higher in crescentic class than non-crescentic class, and correlated with proteinuria level, Birmingham Vasculitis Activity Score and the proportion of crescents in the renal specimen.
The expression of three NLRs was upregulated in kidneys of AAV patients. The expression of NOD2 and NLRC5 was associated with the severity of renal lesions in AAV.
核苷酸结合寡聚化结构域（NOD）样受体（NLRs）是细胞内病原体和受损细胞分子的传感器，可调节固有免疫系统的炎症反应。新出现的证据表明 NLRs 在抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）中可能具有作用。本研究旨在探讨核苷酸结合寡聚化结构域含有蛋白 2（NOD2）、NOD 样受体家族吡啶结构域含有 3（NLRP3）和 NOD 样受体家族 CARD 结构域含有 5（NLRC5）在 AAV 患者肾脏中的表达，并进一步探讨它们与临床和病理参数的关系。
纳入 34 例活动期 AAV 患者。采用免疫组织化学法检测肾脏标本中三种 NLRs 的表达情况，采用双重免疫荧光法检测固有细胞和浸润细胞中的 NLRs。还采用基因表达分析方法检测培养的人足细胞中的 NLRs 表达情况。分析 NLRs 表达与临床病理参数的关系。
与正常对照、微小病变性肾病或 IV 型狼疮性肾炎相比，AAV 患者肾脏中 NOD2、NLRP3 和 NLRC5 的表达明显升高。这些 NLRs 与足细胞和浸润性炎症细胞共定位。新月体性 AAV 患者肾小球中 NOD2 的平均光密度明显高于非新月体性 AAV 患者，且与肾活检时蛋白尿和血清肌酐水平相关。新月体性 AAV 患者肾小球中 NLRC5 的平均光密度明显高于非新月体性 AAV 患者，且与蛋白尿水平、Birmingham 血管炎活动评分和肾标本中新月体的比例相关。
三种 NLRs 在 AAV 患者肾脏中表达上调。NOD2 和 NLRC5 的表达与 AAV 患者肾脏病变的严重程度相关。
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