Glycomic markers of inflammatory bowel disease and IgA nephropathy

Abstract

This thesis investigates how protein glycosylation, the enzyme-controlled attachment of complex carbohydrates to proteins, can improve the understanding, diagnosis, prognosis, and patient stratification of inflammatory bowel disease (IBD) and IgA nephropathy (IgAN).

Plasma protein and immunoglobulin A (IgA) glycosylation were analyzed in Crohn’s disease and ulcerative colitis, two clinically challenging forms of IBD. High-throughput analysis of over 3,500 plasma samples identified glycosylation changes linked to disease severity and treatment response, while IgA-specific signatures showed potential as non-invasive biomarkers for diagnosis and patient stratification.

The thesis also examines IgAN, a kidney disease characterized by aberrant IgA glycosylation and immune-complex deposition. A newly developed mass spectrometry-based approach provided greater detail than conventional lectin assays, confirming known O-glycosylation abnormalities and identifying novel N-glycosylation signatures associated with diagnosis, prognosis, and disease severity. A major contribution of this work is methodological innovation, including automated robotic sample preparation, stabilized sialic acid derivatization, selective IgA enrichment using camelid antibody domains, and advanced MALDI-TOF-MS and LC-ESI-MS workflows for robust large-cohort analyses. Overall, the findings advance glycomic biomarker research and highlight the potential of disease-specific glycosylation signatures to support non-invasive diagnostics and personalized treatment strategies in immune-mediated diseases.