Department Biomedical Engineering, University of Houston, Houston, TX, USA.
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, PR China.
Clin Immunol. 2023 Sep;254:109713. doi: 10.1016/j.clim.2023.109713. Epub 2023 Jul 27.
Due to unique advantages that allow high-dimensional tissue profiling, we postulated imaging mass cytometry (IMC) may shed novel insights on the molecular makeup of proliferative lupus nephritis (LN). This study interrogates the spatial expression profiles of 50 target proteins in LN and control kidneys. Proliferative LN glomeruli are marked by podocyte loss with immune infiltration dominated by CD45RO+, HLA-DR+ memory CD4 and CD8 T-cells, and CD163+ macrophages, with similar changes in tubulointerstitial regions. Macrophages are the predominant HLA-DR expressing antigen presenting cells with little expression elsewhere, while macrophages and T-cells predominate cellular crescents. End-stage sclerotic glomeruli are encircled by an acellular fibro-epithelial Bowman's space surrounded by immune infiltrates, all enmeshed in fibronectin. Proliferative LN also shows signs indicative of epithelial to mesenchymal plasticity of tubular cells and parietal epithelial cells. IMC enabled proteomics is a powerful tool to delineate the spatial architecture of LN at the protein level.
由于具有允许高维组织分析的独特优势，我们推测成像质谱细胞术（IMC）可能会为增生性狼疮肾炎（LN）的分子构成提供新的见解。本研究探讨了 LN 和对照肾脏中 50 种靶蛋白的空间表达谱。增生性 LN 肾小球伴有足细胞丧失，免疫浸润主要由 CD45RO+、HLA-DR+记忆 CD4 和 CD8 T 细胞和 CD163+巨噬细胞组成，肾小管间质区域也有类似的变化。巨噬细胞是主要的 HLA-DR 表达抗原呈递细胞，其他部位表达很少，而巨噬细胞和 T 细胞则占优势细胞新月体。终末期硬化性肾小球被无细胞纤维上皮性鲍曼氏腔环绕，周围有免疫浸润，均被纤维连接蛋白包裹。增生性 LN 还显示出管状细胞和壁细胞上皮到间充质可塑性的迹象。IMC 实现的蛋白质组学是描绘 LN 在蛋白质水平上的空间结构的有力工具。
