Thesis defense Nienke Oskam

On 28 March 2024 (1:00 PM) Sanquin researcher Nienke Oskam defended her PhD thesis Immunoglobulin M: Structure, function and specificity in health and autoimmunity at the University of Amsterdam.

Promotor
Prof S Marieke van Ham PhD

Copromotor
Theo Rispens PhD

Venue
Agnietenkapel, Universiteit van Amsterdam

Add to calendar

Abstract
Immunoglobulin M is the first antibody to be expressed during immune responses, but is also crucially important in maintaining immune homeostasis. This is evidenced by studies that have shown that a failure to produce IgM leads to an abrogated IgG response and to development of autoimmune diseases. Despite these immunoprotective roles, certain pathologies are marked by the presence of IgM autoantibodies or paraproteins, such as Rheumatoid Arthritis (RA) and Waldenström Macroglobulinemia (WM) respectively. Here, the generally self- and polyreactive nature of these antibodies may instead prove detrimental and aggravate inflammation. It is currently unclear what separates these pathogenic IgM (auto)antibodies from their naturally occurring counterparts.
The aim of this thesis was, on the one hand, to characterize structural aspects of antibodies, IgM in particular, and determine the ways these aspects affect their function and possible pathogenicity, with focus on complement activation. Notably, we found that in healthy individuals virtually all IgM circulates as a pentameric molecule in complex with J-chain and CD5L, whereas IgM lacking either seems to be a feature of disease. An additional aim was to characterize the repertoire of a classic (IgM) autoantibody, the rheumatoid factor (RF), in different immune contexts. We show that RFs derived from healthy donors and patients with RA and Sjögren’s disease all target distinct areas on the IgG-Fc. RF responses were further studied in the context of vaccination and infection, poly- autoimmunity and pre-clinical to early onset RA.