BACKGROUND Pentraxin3 (PTX3) is an emerging player in lupus nephritis (LN). Anti-PTX3 antibodies showed to delay LN occurrence in vivo. AIM To evaluate renal changes following immunization with PTX3 in a murine model of LN. MATERIALS AND METHODS Twenty-two lupus-prone New Zealand Black/White (NZB/W)F1 mice were divided into two groups (n = 11) and subcutaneously injected with human recombinant (hr)PTX3 100 μg or phosphate buffer saline (PBS) 200 μl, three times 3 weeks apart, starting before development of proteinuria. Five mice from each group were scheduled for sacrifice at week 22 and 6 from each group at week 29. Renal lesions included electron-dense deposits (EDD), glomerular deposition of IgG, complement and PTX3 as markers of renal inflammation. They were evaluated by immunofluorescence (IF), confocal and immunoelectron microscopy (IEM). Validated semiquantitative scores were used when available to score renal lesions. Chi-squared test with Fisher exact test was used for comparison. RESULTS Nineteen out of 22 mice were sacrificed as scheduled. Only hrPTX3-immunized mice developed anti-PTX3 antibodies. Compared to PBS-injected mice, they displayed a dramatic decrease in glomerular deposits of IgG, C1q and PTX3, as well as in the amount of EDD (p = 0.006) and podocyte effacement (p = 0.043). Importantly, PTX3 was pinpointed inside the EDD and co-localized with nuclear material. CONCLUSIONS Immunization with PTX3 prevented progression from the preclinical to the clinical stage of LN, inciting anti-PTX3 antibodies and preventing renal PTX3 deposition. PTX3 is a novel component of EDD, submitting it as one initiating autoantigen in LN and as potential target for early treatment.

中文翻译：

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Pentraxin3 免疫可防止狼疮易发小鼠从亚临床狼疮肾炎转变为临床狼疮肾炎：肾超微结构发现的见解。

背景 Pentraxin3 (PTX3) 是狼疮性肾炎 (LN) 的新兴参与者。抗 PTX3 抗体显示延迟了体内 LN 的发生。目的 评估 LN 小鼠模型中 PTX3 免疫后的肾脏变化。材料与方法 将 22 只狼疮易发的新西兰黑/白 (NZB/W)F1 小鼠分为两组 (n = 11) 并皮下注射人重组 (hr)PTX3 100 μg 或磷酸盐缓冲盐水 (PBS) 200 μl，间隔 3 周 3 次，在出现蛋白尿之前开始。计划在第 22 周处死每组的 5 只小鼠，并在第 29 周处死每组的第 6 只。肾脏病变包括电子致密沉积物 (EDD)、IgG、补体和 PTX3 作为肾脏炎症标志物的肾小球沉积。它们通过免疫荧光 (IF)、共聚焦和免疫电子显微镜 (IEM) 进行评估。当可以对肾脏病变进行评分时，使用经过验证的半定量评分。卡方检验和 Fisher 精确检验用于比较。结果 22 只小鼠中有 19 只按计划处死。只有 hrPTX3 免疫的小鼠产生了抗 PTX3 抗体。与注射 PBS 的小鼠相比，它们的 IgG、C1q 和 PTX3 的肾小球沉积物以及 EDD 的量（p = 0.006）和足细胞消失（p = 0.043）显着减少。重要的是，PTX3 被精确定位在 EDD 内并与核材料共定位。结论 PTX3 免疫可防止 LN 从临床前到临床阶段的进展，激发抗 PTX3 抗体并防止肾脏 PTX3 沉积。PTX3 是 EDD 的一种新成分，将其作为 LN 中的一种起始自身抗原，并作为早期治疗的潜在靶点。