Integrated urine proteomics and renal single-cell genomics identify an IFN-γ response gradient in lupus nephritis
PublisherThe American Society for Clinical Investigation
MetadataShow full item record
AbstractLupus nephritis, one of the most serious manifestations of systemic lupus erythematosus (SLE), has a heterogeneous clinical and pathological presentation. For example, proliferative nephritis identifies a more aggressive disease class that requires immunosuppression. However, the current classification system relies on the static appearance of histopathological morphology, which does not capture differences in the inflammatory response. Therefore, a biomarker grounded in the disease biology is needed in order to understand the molecular heterogeneity of lupus nephritis and identify immunologic mechanism and pathways. Here, we analyzed the patterns of 1000 urine protein biomarkers in 30 patients with active lupus nephritis. We found that patients stratify over a chemokine gradient inducible by IFN-?. Higher values identified patients with proliferative lupus nephritis. After integrating the urine proteomics with the single-cell transcriptomics of kidney biopsies, we observed that the urinary chemokines defining the gradient were predominantly produced by infiltrating CD8+ T cells, along with natural killer and myeloid cells. The urine chemokine gradient significantly correlated with the number of kidney-infiltrating CD8+ cells. These findings suggest that urine proteomics can capture the complex biology of the kidney in lupus nephritis. Patient-specific pathways could be noninvasively tracked in the urine in real time, enabling diagnosis and personalized treatment.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85086748812&doi=10.1172%2fjci.insight.138345&partnerID=40&md5=65555ff595c9124b7c96dc8efbab1588; http://hdl.handle.net/10713/13207
- CXCR3+CD4+ T cells are enriched in inflamed kidneys and urine and provide a new biomarker for acute nephritis flares in systemic lupus erythematosus patients.
- Authors: Enghard P, Humrich JY, Rudolph B, Rosenberger S, Biesen R, Kuhn A, Manz R, Hiepe F, Radbruch A, Burmester GR, Riemekasten G
- Issue date: 2009 Jan
- 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.
- Authors: Bertolo M, Baumgart S, Durek P, Peddinghaus A, Mei H, Rose T, Enghard P, Grützkau A
- Issue date: 2020
- Urinary angiostatin, CXCL4 and VCAM-1 as biomarkers of lupus nephritis.
- Authors: Mok CC, Soliman S, Ho LY, Mohamed FA, Mohamed FI, Mohan C
- Issue date: 2018 Jan 11
- Serum and Urinary Interferon-Gamma-Inducible Protein 10 in Lupus Nephritis.
- Authors: El-Gohary A, Hegazy A, Abbas M, Kamel N, Nasef SI
- Issue date: 2016 Nov
- Mapping urinary chemokines in human lupus nephritis: Potentially redundant pathways recruit CD4<sup>+</sup> and CD8<sup>+</sup> T cells and macrophages.
- Authors: Klocke J, Kopetschke K, Grießbach AS, Langhans V, Humrich JY, Biesen R, Dragun D, Radbruch A, Burmester GR, Riemekasten G, Enghard P
- Issue date: 2017 Jan