PhD defence
Glycomic Markers of Inflammatory Bowel Disease and IgA Nephropathy
- F. Clerc
- Date
- Wednesday 9 September 2026
- Time
- Location
-
Academy Building
Rapenburg 73
2311 GJ Leiden
Supervisor(s)
- Prof.dr. M. Wuhrer
Summary
Protein glycosylation, i.e. the enzyme-controlled attachment of branched carbohydrate structures to proteins, plays a central role in protein stability, cellular communication, immune recognition, inflammation, and disease. This thesis explores whether disease-associated glycosylation patterns can improve understanding, diagnosis, prognosis, and patient stratification in inflammatory bowel disease (IBD) and IgA nephropathy (IgAN).
This thesis starts with an overview of the glycosylation of twenty-five most abundant human plasma glycoproteins, and then examines plasma protein and immunoglobulin A (IgA) glycosylation in Crohn’s disease and ulcerative colitis. Distinguishing these two major forms of IBD remains clinically challenging, despite important differences in their treatment. High-throughput analysis of more than 3’500 plasma samples revealed changes in glycosylation associated with disease severity and treatment response. Additionally, IgA-specific signatures proved to be promising leads for early non-invasive diagnosis and improved patient stratification.
The thesis also investigates IgAN, a progressive kidney disease characterized by abnormal IgA glycosylation and immune-complex deposition. The newly developed mass-spectrometry method used here offers greater information than the conventional lectin-based assays and reveals both established O-glycosylation abnormalities and novel N-glycosylation signatures associated with disease severity, diagnosis, and prognosis.
Methodological innovation is a central aspect of this work. Automated robotic sample preparation, sialic-acid stabilization, selective IgA capture using immobilized camelid antibody domains, and advanced MALDI-TOF-MS and LC-ESI-MS workflows enabled reproducible, scalable analysis of large patient cohorts.
Overall, this thesis advances glycomic biomarker research and demonstrates the potential of disease-specific glycosylation signatures to support non-invasive diagnostics, personalized treatment decisions, and provides leads for future studies of immune-mediated diseases.
PhD dissertations
Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.
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General information
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