Break of immunological tolerance is at the basis of the development of autoimmunity and consequently autoimmune diseases. We aim to understand how B-cell tolerance towards self-antigens is broken. Emphasis is given to B-cells and auto-antibodies recognizing post-translationally modified protein-antigens in rheumatoid arthritis. However, also other B-cell- and auto-antibody responses present in other rheumatic diseases are studied. We thrive to implement the knowledge acquired on the breach of tolerance and the evolution of human auto-reactive B-cell responses into the design of preventive strategies and/or interventions aiming to restore normal immune-homeostasis against autoantigens and ultimately cure of B-cell mediated auto-immune diseases.
Department of Rheumatology, LUMC Leiden, The Netherlands
Scherer HU, Huizinga TWJ, Kronke G, Schett G, Toes REM. The B cell response to citrullinated antigens in the development of rheumatoid arthritis. Nat Rev Rheumatol. 2018.
Vergroesen RD, Slot LM, Hafkenscheid L, Koning MT, van der Voort EIH, Grooff CA, Zervakis G, Veelken H, Huizinga TWJ, Rispens T, et al. B-cell receptor sequencing of anti-citrullinated protein antibody (ACPA) IgG-expressing B cells indicates a selective advantage for the introduction of N-glycosylation sites during somatic hypermutation. Ann Rheum Dis. 2017.
Dekkers JS, Verheul MK, Stoop JN, Liu B, Ioan-Facsinay A, van Veelen PA, de Ru AH, Janssen GMC, Hegen M, Rapecki S, et al. Breach of autoreactive B cell tolerance by post-translationally modified proteins. Ann Rheum Dis. 2017.
Rombouts Y, Willemze A, van Beers JJ, Shi J, Kerkman PF, van Toorn L, Janssen GM, Zaldumbide A, Hoeben RC, Pruijn GJ, et al. Extensive glycosylation of ACPA-IgG variable domains modulates binding to citrullinated antigens in rheumatoid arthritis. Ann Rheum Dis. 2016.
van Heemst J, Jansen DT, Polydorides S, Moustakas AK, Bax M, Feitsma AL, Bontrop-Elferink DG, Baarse M, van der Woude D, Wolbink GJ, et al. Crossreactivity to vinculin and microbes provides a molecular basis for HLA-based protection against rheumatoid arthritis. Nat Commun. 2015.
Priscilla Kerkman: Identification and characterisation of anti-citrullinated protein antibody (ACPA)-producing B cells in patients with rheumatoid arthritis (RA). Awarded: 2017
Diahann Jansen: Functional aspects of the adapative immune system in arthritis. Awarded: 2017
Hanane El Bannoudi: Immune regulation by CD49b+ CD4+ T cells & modulation of B cell responses. Awarded: 2016
Jing Shi: Anti-Carbamylated Protein Antibodies in Rheumatoid Arthritis. Awarded: 2016
Jurgen van Heemst: Towards a molecular basis for the association of HLA, Rheumatoid Arthritis and Autoantibodies. Awarded: 2015
Annemiek Willemze: The influence of autoantibody status and characteristics on the course of Rheumatoid Arthritis. Awarded: 2014
Uli Scherer: Basic disease mechanisms in Rheumatoid Arthritis. Awarded: 2013
Parawee Suwannalai: ACPA response in evolution of Rheumatoid Arthritis. Awarded: 2012
Diane van der Woude: Anti-Citrullinated Protein Antibodies (ACPA) in rheumatoid arthritis, linking genetic predisposition to clinical outcome. Awarded: 2012
Current PhD projects
Marije Verheul: Anti-Carbamylated Protein-antibodies in rheumatic disease; studies on antibodies and antigens
Ayla Kempers: The Anti-Citrullinated Protein Antibody immune response and its effector functions in Rheumatoid Arthritis
Lise Hafkenscheid: ACPA-Fab-glycosylation as marker for disease
Sanne Kampstra: Breach of auto-reactive B cell tolerance by post-translationally modified proteins
Hendy Kristyanto: Functional characterization of citrullinated-antigen-specific (memory) B cells and the development of strategies for antigen-specific depletion
Myrthe van Delft: Immunological properties of the anti-CarP antibody response
Jacqueline Dekkers: How is tolerance towards carbamylated proteins broken and does anti-CarP immunity contribute to arthritis?
Emma de Moel: Etiological, prognostic and theragnostic significance of autoantibodies in rheumatoid arthritis
Corrie Wortel: Identification and characterisation of auto-reactive B cells in systemic auto-immune diseases
Rochelle Vergroesen: The B cell receptor repertoire of citrullinated antigen-directed B cells in RA
Theresa Kissel: On the origin of species: dissecting Anti-Modified Protein Antibodies in Rheumatoid Arthritis
Mikhail Volkov: The effect of risk factors on the cellular and serological immunopathology underlying rheumatoid arthritis.