Glycan biomarker panels in liquid biopsies for predicting treatment response in lupus nephritis

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Lupus nephritis (LN), an immune complex-mediated glomerulonephritis, affects up to two-thirds of patients with systemic lupus erythematosus. Despite standard treatment protocols, progression of the most aggressive forms of LN (class III and IV) to end-stage renal failure remains high. Thus, there is a need for biomarkers of therapeutic response that would allow physicians to make better-informed treatment decisions for LN patients. To address this, our proposal builds upon ongoing collaborations between a clinical nephrology group at MUSC with an extensive LN biorepository of control and treatment samples with clinical metadata and GlycoPath Inc., a diagnostic company developing unique glycosylation targeted liquid biopsy assays. GlycoPath has recently patented, licensed and published a streamlined antibody capture slide array approach, GlycoTyper, to directly profile N-glycans of captured serum and plasma glycoproteins including imm unoglobulin G (IgG) subtypes. An adaption of the GlycoTyper platform has also been developed to rapidly obtain total glycan profiles of biofluids like serum and urine. Using this approach, several cohorts of patient matched serum and urine from control and LN subjects 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 can use glycan panels to distinguish control from LN conditions, we hypothesize that this assay can be applied to monitor treatment response in biofluids from subjects treated with standard-of-care therapies like mycophenolate mofetil (MMF). In this Phase I STTR application, we propose to establish the technical merit and feasibility of Glycotyper-LNTx for monitoring LN treatment responses. Aim 1 will validate N-glycan profiles in urine samples from LN subjects for MMF treatment response at time zero, 3 months and 12 months of treatment. Aim 2 will identify IgG specific N-glycan profiles in patient matched serum and urine samples with follow up application in a LN treatment response cohort. This study will establish and validate a LN specific liquid biopsy glycan biomarker assay for use in monitoring disease status and therapeutic response.