Macrophages play an important role in the pathogenesis of lupus nephritis (LN), but less is known about macrophage subtypes in pediatric LN. Here we compared renal inflammation in LN with other inflammatory pediatric kidney diseases and assessed whether inflammation correlates with clinical parameters. Using immunofluorescence microscopy, we analyzed renal biopsies from 20 pediatric patients with lupus nephritis (ISN/RPS classes II–V) and pediatric controls with other inflammatory kidney diseases for infiltration with M1-like (CD68 + /CD206 − , CD68 + /CD163 −), M2a-like (CD206 + /CD68 +), and M2c-like macrophages (CD163 + /CD68 +) as well as CD3 + T-cells, CD20 + B-cells, and MPO + neutrophilic granulocytes. In addition, the correlation of macrophage infiltration with clinical parameters at the time of renal biopsy, e.g., eGFR and serum urea, was investigated. Macrophage subpopulations were compared with data from a former study of adult LN patients. The frequency of different macrophage subtypes in biopsies of pediatric LN was dependent on ISN/RPS class and showed the most pronounced M1-like macrophage infiltration in patients with LN class IV, whereas M2c-like macrophages were most abundant in class III and IV. Interestingly, on average, only half as many macrophages were found in renal biopsies of pediatric LN compared to adult patients with LN. The distribution of frequencies of macrophage subpopulations, however, was different for CD68 + CD206 + (M2a-like) but comparable for CD68 + CD163 − (M1-like) CD68 + CD163 + (M2c-like) cells in pediatric and adult patients. Compared to other inflammatory kidney diseases in children, fewer macrophages and other inflammatory cells were found in kidney biopsies of LN. Depending on the disease, the frequency of individual immune cell types varied, but we were unable to confirm disease-specific inflammatory signatures in our study due to the small number of pediatric cases. Worsened renal function, measured as elevated serum urea and decreased eGFR, correlated particularly strongly with the number of CD68 + /CD163 − M1-like macrophages and CD20 + B cells in pediatric inflammatory kidney disease. Although M1-like macrophages play a greater role in pediatric LN patients than in adult LN patients, M2-like macrophages appear to be key players and are more abundant in other pediatric inflammatory kidney diseases compared to LN.

中文翻译：

---

狼疮性肾炎和其他影响肾脏的炎症性疾病儿童患者的巨噬细胞亚群

巨噬细胞在狼疮性肾炎 (LN) 的发病机制中发挥着重要作用，但人们对儿童狼疮性肾炎中的巨噬细胞亚型知之甚少。在这里，我们将 LN 的肾脏炎症与其他炎症性儿科肾脏疾病进行比较，并评估炎症是否与临床参数相关。使用免疫荧光显微镜，我们分析了 20 名狼疮性肾炎儿科患者（ISN/RPS II-V 类）和患有其他炎症性肾病的儿科对照患者的肾活检，以了解 M1 样浸润（CD68 + /CD206 − 、CD68 + /CD163 − )、M2a 样巨噬细胞 (CD206 + /CD68 +) 和 M2c 样巨噬细胞 (CD163 + /CD68 +) 以及 CD3 + T 细胞、CD20 + B 细胞和 MPO + 中性粒细胞。此外，还研究了巨噬细胞浸润与肾活检时的临床参数（例如eGFR和血清尿素）的相关性。将巨噬细胞亚群与之前一项针对成人 LN 患者的研究数据进行了比较。儿童 LN 活检中不同巨噬细胞亚型的频率取决于 ISN/RPS 类别，并且在 IV 级 LN 患者中显示最明显的 M1 样巨噬细胞浸润，而在 III 级和 IV 级患者中 M2c 样巨噬细胞最丰富。有趣的是，平均而言，儿童 LN 肾活检中发现的巨噬细胞数量仅为成人 LN 患者的一半。然而，儿科和成人患者中 CD68 + CD206 + （M2a 样）巨噬细胞亚群的频率分布不同，但 CD68 + CD163 − （M1 样）CD68 + CD163 + （M2c 样）细胞的频率分布相当。与儿童其他炎症性肾脏疾病相比，LN 肾活检中发现的巨噬细胞和其他炎症细胞较少。根据疾病的不同，个体免疫细胞类型的频率有所不同，但由于儿科病例数量较少，我们无法在我们的研究中确认疾病特异性的炎症特征。在儿童炎症性肾病中，肾功能恶化（以血清尿素升高和 eGFR 降低为衡量标准）与 CD68 + /CD163 - M1 样巨噬细胞和 CD20 + B 细胞的数量密切相关。尽管 M1 样巨噬细胞在儿童 LN 患者中比在成人 LN 患者中发挥更大的作用，但 M2 样巨噬细胞似乎是关键参与者，并且与 LN 相比，M2 样巨噬细胞在其他儿童炎症性肾病中更为丰富。