Lupus nephritis (LN), an immune complex-mediated glomerulonephritis, affects up to two-thirds ofpatients with systemic lupus erythematosus. Despite standard treatment protocols, progression of themost aggressive forms of LN (class III and IV) to end-stage renal failure remains high. Thus, there is aneed for biomarkers of therapeutic response that would allow physicians to make better-informedtreatment decisions for LN patients. To address this, our proposal builds upon ongoing collaborationsbetween a clinical nephrology group at MUSC with an extensive LN biorepository of control and treatmentsamples with clinical metadata and GlycoPath Inc., a diagnostic company developing uniqueglycosylation targeted liquid biopsy assays. GlycoPath has recently patented, licensed and published astreamlined antibody capture slide array approach, GlycoTyper, to directly profile N-glycans of capturedserum and plasma glycoproteins including imm unoglobulin G (IgG) subtypes. An adaption of theGlycoTyper platform has also been developed to rapidly obtain total glycan profiles of biofluids like serumand urine. Using this approach, several cohorts of patient matched serum and urine from control and LNsubjects have been evaluated for N-linked glycan constituents. A distinct panel of LN associated N-glycans have already been identified and serve as the basis for the proposed studies. Because we canuse glycan panels to distinguish control from LN conditions, we hypothesize that this assay can beapplied to monitor treatment response in biofluids from subjects treated with standard-of-care therapieslike mycophenolate mofetil (MMF). In this Phase I STTR application, we propose to establish the technicalmerit and feasibility of Glycotyper-LNTx for monitoring LN treatment responses. Aim 1 will validate N-glycanprofiles in urine samples from LN subjects for MMF treatment response at time zero, 3 months and 12 monthsof treatment. Aim 2 will identify IgG specific N-glycan profiles in patient matched serum and urine sampleswith follow up application in a LN treatment response cohort. This study will establish and validate a LN specificliquid biopsy glycan biomarker assay for use in monitoring disease status and therapeutic response.
Public Health Relevance Statement: Project Narrative
This joint project between MUSC and GlycoPath Inc will establish the feasibility of using N-
glycan analysis of urine and captured immunoglobulins from urine as biomarkers of treatment
response in lupus nephritis patients
Project Terms: <7S Gamma Globulin> |
