- Standing out of the crowd
- Adaptive immune cells in the pathogenesis and prediction of rheumatoid arthritis and IgG4-related disease
N. de Vries
- Award date
- 1 June 2017
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
Both rheumatoid arthritis (RA) and IgG4-related disease (IgG4-RD) are chronic and debilitating immune-mediated inflammatory disorders (IMIDs). Although current therapies ameliorate disease symptoms, tissue damage is inevitable, disease relapse is common and therapies do not provide cure. In both diseases, two main groups of shared unmet needs can be discerned: 1) markers that help us manage the disease more effectively, and 2) insight into and understanding of the pathogenesis. With these unmet needs in mind, in this thesis I explored the use of state-of-the-art technology to advance patient care. In RA, multiple dominant T- and B-cell receptor clones are present in inflamed synovial tissue. Analysis in the pre-clinical phase of RA shows many dominant B-cell receptor clones in blood, but these clones will only become apparent in synovial tissue after arthritis developed. The presence of dominant B-cell receptor clones in blood predicts the development of rheumatoid arthritis within 3 years. In IgG4-RD, multiple expanded IgG4+-BCR clones are present in affected tissue and peripheral blood, while these were absent in control patients with comparable clinical presentation. After treatment, the clones selectively disappeared from blood. The presence of dominant IgG4+-B-cell receptor clones can be used to diagnose IgG4-RD of the pancreas and biliary tree. In both RA and IgG4-RD, T- and B-cell receptor clones with distinct features stand out of the crowd of the total antigen-receptor repertoire, and their presence has diagnostic and predictive value. It improves our understanding of the pathogenesis of both diseases, and fuels the development of more effective and preventative strategies.
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