对抗磷脂抗体阳性患者进行哺乳动物雷帕霉素靶途径评估

Pub Date : 2022-09-01 Epub Date: 2022-06-01 DOI:10.3899/jrheum.220049
Ecem Sevim, Salma Siddique, Madhavi Latha S Chalasani, Susan Chyou, William D Shipman, Orla O'Shea, Joanna Harp, Oral Alpan, Stéphane Zuily, Theresa T Lu, Doruk Erkan
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引用次数: 0

摘要

目的:在抗磷脂抗体(aPL)肾病中,雷帕霉素哺乳动物靶标(mTOR)的激活有助于内皮细胞增殖,这是aPL微血管疾病的一个关键发现。在此,我们研究了 aPL 阳性的存活患者皮肤中的 mTOR 激活情况:方法:研究了三组生活化患者:(1)持续 aPL 阳性并伴有系统性红斑狼疮(SLE)的患者;(2)持续 aPL 阳性但无系统性红斑狼疮的患者;(3)aPL 阴性的系统性红斑狼疮患者(对照组)。在收集了与 aPL 相关的病史后,我们对每位患者进行了两次 5 毫米的活组织皮肤切片检查:(1) 周围(红斑-皮损);(2) 中央(非皮损区域)。我们对标本进行了染色,以检测磷酸化蛋白激酶B(p-AKT)和磷酸化S6核糖体蛋白(p-S6RP)作为mTOR活性标记,CD31用于识别内皮细胞,Ki-67用于显示细胞增殖。我们对表皮中的细胞进行了计数,并使用弗里德曼检验和Wilcoxon符号秩检验比较了外周样本和中心样本以及不同患者组之间的mTOR阳性细胞计数:结果:共纳入了 10 名网状组织病患者:4例aPL阳性但无系统性红斑狼疮(符合抗磷脂综合征[APS]分类,n = 3),4例aPL阳性系统性红斑狼疮(符合APS分类,n = 3),2例aPL阴性系统性红斑狼疮(对照组)。与 aPL 阴性的系统性红斑狼疮对照组相比,在所有 aPL 阳性患者的外周和中央皮肤样本中,表皮 p-AKT 和 p-S6RP 染色均显著增加;两者在表皮基底层更明显:我们的研究表明,与 aPL 阴性的系统性红斑狼疮患者相比,aPL 阳性或非 aPL 阳性的系统性红斑狼疮患者活体皮损中的 mTOR 活性增加,表皮基底层的活性更为突出。这些发现可为进一步研究 aPL 阳性患者的 mTOR 通路提供依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mammalian Target of Rapamycin Pathway Assessment in Antiphospholipid Antibody-Positive Patients with Livedo.

Objective: In antiphospholipid antibody (aPL) nephropathy, activation of the mammalian target of rapamycin (mTOR) contributes to endothelial cell proliferation, a key finding of aPL microvascular disease. Here, we examined mTOR activation in the skin of aPL-positive patients with livedo.

Methods: Three patient groups with livedo were studied: (1) persistently aPL-positive with systemic lupus erythematosus (SLE); (2) persistently aPL-positive without SLE; and (3) aPL-negative SLE (control). After collecting aPL-related medical history, two 5-mm skin biopsies of livedo were performed on each patient: (1) peripheral (erythematous-violaceous lesion); and (2) central (nonviolaceous area). We stained specimens for phosphorylated protein kinase B (p-AKT) and phosphorylated S6 ribosomal protein (p-S6RP) as mTOR activity markers, CD31 to identify endothelial cells, and Ki-67 to show cellular proliferation. We counted cells in the epidermis and compared mTOR-positive cell counts between peripheral and central samples, and between patient groups, using Freidman test and Wilcoxon signed-rank test.

Results: Ten patients with livedo reticularis were enrolled: 4 aPL-positive without SLE (antiphospholipid syndrome [APS] classification met, n = 3), 4 aPL-positive SLE (APS classification met, n = 3), and 2 aPL-negative SLE (control). In all aPL-positive patients, epidermal p-AKT and p-S6RP staining were significantly increased in both peripheral and central skin samples when compared to aPL-negative SLE controls; both were more pronounced in the lower basal layers of epidermis.

Conclusion: Our study demonstrates increased mTOR activity in livedoid lesions of aPL-positive patients with or without SLE compared to aPL-negative patients with SLE, with more prominent activity in the lower basal layers of the epidermis. These findings may serve as a basis for further investigating the mTOR pathway in aPL-positive patients.

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