title: Molecular imaging of the kidney in lupus nephritis to characterize response to treatment.
abstract: The consequences of treatment for the kidney at the molecular level have not been explored in human lupus nephritis (LN). In this investigation, changes in intrarenal transcript expression were measured and correlated with response in a LN cohort that underwent serial kidney biopsies. The intrarenal transcript expression of 19 patients with proliferative LN (Class III or IV) was measured at diagnostic biopsy (Bx1) and after induction therapy was completed (Bx2) using Nanostring technology. Patients were segregated by clinical response into complete responders (n = 5, CR) or nonresponders (n = 4, NR). Transcript expression for each biopsy was compared with normal controls (n = 4), and the change in expression was compared in each responder group and between groups. Compared with controls, the CR group had 21 and 28, whereas NR had 45 and 103 differentially-expressed transcripts at Bx1 and Bx2, respectively. The profiles of these differentially-expressed genes indicated that the type I and II interferon, alternative complement and T cell signaling pathways discriminated CR from NR. Comparing the change in transcript expression from Bx1 to Bx2 revealed a 5-gene signature that differentiated NR from CR and included increased IL1RAP and FCAR in NR and increased NCAM1 in CR. In summary, molecular imaging of serial kidney biopsies from LN patients shows several immune and inflammatory pathways that are dysregulated in the kidneys during active disease that may serve as therapeutic targets to improve clinical response. This approach to LN biomarker development may facilitate personalized medicine in LN and improve long-term kidney outcomes.
authors.affiliation: Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio.
authors.forename: Samir V
authors.initials: SV
authors.lastname: Parikh
authors.affiliation: Nephrology Unit, Hospital Fernandez, Buenos Aires, Argentina.
authors.forename: Ana
authors.initials: A
authors.lastname: Malvar
authors.affiliation: Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Pathology, Hospital Fernandez, Buenos Aires, Argentina.
authors.forename: Valeria
authors.initials: V
authors.lastname: Alberton
authors.affiliation: Nephrology Unit, Hospital Fernandez, Buenos Aires, Argentina.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lococo
authors.affiliation: Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio.
authors.forename: Jay
authors.initials: J
authors.lastname: Vance
authors.affiliation: Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, Ohio.
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, Ohio.
authors.forename: Lianbo
authors.initials: L
authors.lastname: Yu
authors.affiliation: Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio.
authors.forename: Dan
authors.initials: D
authors.lastname: Birmingham
authors.affiliation: Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio. Electronic address: rovin.1@osu.edu.
authors.forename: Brad H
authors.initials: BH
authors.lastname: Rovin
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D003165:Complement System Proteins / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007372:Interferons / Q000378:metabolism; D007668:Kidney / Q000473:pathology*; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D003165:Complement System Proteins; D007372:Interferons