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系统生物学的力量:从加速药物研发伙伴关系中获得的狼疮肾炎的见解。

The Power of Systems Biology: Insights on Lupus Nephritis from the Accelerating Medicines Partnership.

机构信息

Division of Rheumatology, Johns Hopkins University, 1830 East Monument Street, Suite 7500, Baltimore, MD 21205, USA.

Division of Rheumatology, Inflammation, Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Center for Data Sciences, Brigham and Women's Hospital, Building for Transformative Medicine, 60 Fenwood Road, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, Manchester, UK. Electronic address: https://twitter.com/soumya_boston.

出版信息

Rheum Dis Clin North Am. 2021 Aug;47(3):335-350. doi: 10.1016/j.rdc.2021.04.003. Epub 2021 Jun 16.

DOI:10.1016/j.rdc.2021.04.003
PMID:34215367
Abstract

The Accelerating Medicines Partnership (AMP) SLE Network united resources from academic centers, government, nonprofit, and industry to accelerate discovery in lupus nephritis (LN). The AMP SLE Network developed a set of protocols for high-throughput analyses to systematically study kidney tissue, urine, and blood in LN. This article summarizes approaches and results from phase 1 of AMP SLE Network effort, including single cell RNA-seq analysis of LN kidney biopsies, cellular and proteomic studies of LN urine, and mass cytometry immunophenotyping of blood cells. This work provides a framework to guide studies of the clinical implications of active cellular/molecular pathways in LN.

摘要

加速药物研发合作组织 (AMP) 狼疮网络联合了学术中心、政府、非营利组织和工业界的资源,以加速狼疮肾炎 (LN) 的发现。AMP 狼疮网络制定了一套高通量分析方案,用于系统地研究 LN 肾组织、尿液和血液。本文总结了 AMP 狼疮网络第一阶段的工作方法和结果,包括 LN 肾活检的单细胞 RNA-seq 分析、LN 尿液的细胞和蛋白质组学研究,以及血液细胞的质谱细胞免疫表型分析。这项工作为研究 LN 中活跃的细胞/分子途径的临床意义提供了框架。

相似文献

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The Power of Systems Biology: Insights on Lupus Nephritis from the Accelerating Medicines Partnership.系统生物学的力量:从加速药物研发伙伴关系中获得的狼疮肾炎的见解。
Rheum Dis Clin North Am. 2021 Aug;47(3):335-350. doi: 10.1016/j.rdc.2021.04.003. Epub 2021 Jun 16.
2
Accelerating Medicines Partnership: Organizational Structure and Preliminary Data From the Phase 1 Studies of Lupus Nephritis.加速药物研发合作组织:狼疮肾炎 1 期研究的组织结构和初步数据。
Arthritis Care Res (Hoboken). 2020 Feb;72(2):233-242. doi: 10.1002/acr.24066. Epub 2020 Jan 13.
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Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis.狼疮肾炎的组织学类型、活动度、慢性度和治疗反应的尿蛋白质组学特征。
JCI Insight. 2024 Jan 23;9(2):e172569. doi: 10.1172/jci.insight.172569.
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Deep Phenotyping of Urinary Leukocytes by Mass Cytometry Reveals a Leukocyte Signature for Early and Non-Invasive Prediction of Response to Treatment in Active Lupus Nephritis.采用液质联用技术对尿液白细胞进行深度表型分析,揭示了白细胞特征可早期、无创预测狼疮肾炎治疗应答。
Front Immunol. 2020 Mar 24;11:256. doi: 10.3389/fimmu.2020.00256. eCollection 2020.
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Urinary markers differentially associate with kidney inflammatory activity and chronicity measures in patients with lupus nephritis.尿标志物与狼疮肾炎患者肾脏炎症活动和慢性程度指标的相关性不同。
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Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network.狼疮患者在临床指征下进行肾活检时获取研究组织的安全性:加速药物研发合作组织 RA/SLE 网络的数据。
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Association of Urine sCD163 With Proliferative Lupus Nephritis, Fibrinoid Necrosis, Cellular Crescents and Intrarenal M2 Macrophages.尿液 sCD163 与增生性狼疮肾炎、纤维素样坏死、细胞性新月体及肾内 M2 巨噬细胞的关系。
Front Immunol. 2020 Apr 15;11:671. doi: 10.3389/fimmu.2020.00671. eCollection 2020.

引用本文的文献

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Blood immunophenotyping identifies distinct kidney histopathology and outcomes in patients with lupus nephritis.血液免疫表型分析可识别狼疮性肾炎患者不同的肾脏组织病理学特征及预后情况。
J Clin Invest. 2025 Jun 19. doi: 10.1172/JCI181034.
2
Extrarenal symptoms associate with worse quality of life in patients enrolled in the AMP RA/SLE Lupus Nephritis Network.在参加AMP RA/SLE狼疮性肾炎网络研究的患者中,肾外症状与较差的生活质量相关。
Rheumatology (Oxford). 2025 Mar 1;64(3):1193-1200. doi: 10.1093/rheumatology/keae189.
3
Urinary biomarkers associated with podocyte injury in lupus nephritis.
狼疮性肾炎中与足细胞损伤相关的尿液生物标志物。
Front Pharmacol. 2024 Jan 19;15:1324540. doi: 10.3389/fphar.2024.1324540. eCollection 2024.
4
Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis.狼疮肾炎的组织学类型、活动度、慢性度和治疗反应的尿蛋白质组学特征。
JCI Insight. 2024 Jan 23;9(2):e172569. doi: 10.1172/jci.insight.172569.
5
Urine proteomic insights from the belimumab in lupus nephritis trial.狼疮肾炎试验中的贝利尤单抗的尿液蛋白质组学见解。
Lupus Sci Med. 2022 Sep;9(1). doi: 10.1136/lupus-2022-000763.
6
High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership.在加速药物研发合作组织中,伴有低蛋白尿的 SLE 患者中增殖性和膜性肾炎的发病率较高。
Rheumatology (Oxford). 2022 Nov 2;61(11):4335-4343. doi: 10.1093/rheumatology/keac067.
7
Urine Proteomics and Renal Single-Cell Transcriptomics Implicate Interleukin-16 in Lupus Nephritis.尿液蛋白质组学和肾脏单细胞转录组学提示白细胞介素-16 在狼疮肾炎中的作用。
Arthritis Rheumatol. 2022 May;74(5):829-839. doi: 10.1002/art.42023. Epub 2022 Apr 16.