Show simple item record

dc.contributor.authorZhang, Y.
dc.contributor.authorMagder, L.
dc.contributor.authorAccelerating Medicines Partnership in SLE network
dc.date.accessioned2020-06-30T18:46:32Z
dc.date.available2020-06-30T18:46:32Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85086748812&doi=10.1172%2fjci.insight.138345&partnerID=40&md5=65555ff595c9124b7c96dc8efbab1588
dc.identifier.urihttp://hdl.handle.net/10713/13207
dc.description.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-γ. 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.en_US
dc.description.urihttps://doi.org/10.1172/jci.insight.138345en_US
dc.language.isoen_USen_US
dc.publisherThe American Society for Clinical Investigationen_US
dc.relation.ispartofJCI insight
dc.subjectAutoimmunityen_US
dc.subjectLupusen_US
dc.subjectNephrologyen_US
dc.subjectProteomicsen_US
dc.subjectTh1 responseen_US
dc.titleIntegrated urine proteomics and renal single-cell genomics identify an IFN-γ response gradient in lupus nephritisen_US
dc.typeArticleen_US
dc.identifier.doi10.1172/jci.insight.138345
dc.identifier.pmid32396533


This item appears in the following Collection(s)

Show simple item record