Poster Presentation AUS-oMicS 2025

GlycoTyper™ - a novel liquid-biopsy platform for high-throughput, high-sensitivity targeted glycoproteomics, exemplified be differentiating Systemic Lupus Erythematosus and Lupus Nephritis   (121800)

Steve Wilson 1 , Gary Huffman 2 , Grace Grimsley 2 , Aaron Angerstein 3 , Tamara Nowling 4 , Steve Castellino 2 , Klaus Lindpainter 2
  1. Bruker, Melbourne, VIC, Australia
  2. Bruker Scientific LLC, Billerica, MA, USA
  3. Medical University of South Carolina, Charleston, SC, USA
  4. Pharmacology&Immunology, Medical University of South Carolina, Charleston, SC, USA

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by autoantibody-associated immune-complex formation. Deposition of these immune complexes in the glomeruli can lead to the development of Lupus Nephritis (LN), and, ultimately, kidney failure. To prevent this, early LN diagnosis and immunosuppressive therapy are of critical importance. Presently, LN diagnosis relies on renal biopsy an invasive procedure with frequent complications, as no alternative liquid-biopsy-based approaches are currently available. Given the known association between abnormal immunoglobulin G (IgG) glycosylation and LN, a high-throughput method for characterizing IgG-derived glycans in body fluids represents an important currently unmet medical need.  Here, we introduce the GlycoTyper™ liquid biopsy platform, a MALDI-MS-based method for N-glycan analysis from patient biofluid samples.

Using the GlycoTyper platform, baseline IgG-derived N-glycan profiles were generated from urine samples from 114 healthy controls (HC), 116 SLE patients without kidney disease, and 210 LN patients. Additionally, baseline, 3-month, and 12-month urine samples of 178 LN patients randomly assigned to one of three immunosuppression regimens (mycophenolate mofetil (MMF); MMF + 10 mg/kg Abatacept (ABA); MMF + 30 mg/kg ABA) and urine samples from the were analyzed to interrogate possible N-glycan changes associated with treatment effects or renal disease outcome. 

From the treatment-associated time-course data, four N-glycans were identified whose relative abundances had statistically significant associations with renal disease outcomes defined by urine protein-to-creatinine ratio. Among these, higher relative abundances of 2 biantennary sialylated glycans were associated with non-responder status at the study’s conclusion. Conversely, higher relative abundances of 2 agalactosylated N-glycans were associated with patient responder status. Furthermore, a paired-samples Wilcoxon test identified sixteen N-glycans with statistically significant differences in their relative abundances between the 0th and 12-month time point, indicating a treatment-associated change in N-glycan expression, independent of disease outcome.