Most autoimmune diseases are driven (and potentially initiated) by the presence of pathogenic B and plasma cells as well as their secreted products, autoantibodies. My work centers on the role of human auto-reactive B cells in the pathogenesis of these diseases. We focus on rheumatoid arthritis and the immune response to post-translationally modified proteins as a model, and have a specific interest in the glycosylation of autoantibodies, in particular in the variable domain. My group has developed specific methodology to identify, isolate and characterize human auto-reactive B cells. We use this tool to understand mechanisms underlying the breach of tolerance to auto-antigens, and aim at developing ways for specific therapeutic targeting of pathogenic B cell memory.
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.
Kerkman PF, Kempers AC, van der Voort EI, van Oosterhout M, Huizinga TW, Toes RE, Scherer HU. Synovial fluid mononuclear cells provide an environment for long-term survival of antibody-secreting cells and promote the spontaneous production of anti-citrullinated protein antibodies. Ann Rheum Dis. 2016.
Kerkman PF, Fabre E, van der Voort EI, Zaldumbide A, Rombouts Y, Rispens T, Wolbink G, Hoeben RC, Spits H, Baeten DL, et al. Identification and characterisation of citrullinated antigen-specific B cells in peripheral blood of patients with rheumatoid arthritis. Ann Rheum Dis. 2016.
Rombouts Y, Ewing E, van de Stadt LA, Selman MH, Trouw LA, Deelder AM, Huizinga TW, Wuhrer M, van Schaardenburg D, Toes RE, et al. Anti-citrullinated protein antibodies acquire a pro-inflammatory Fc glycosylation phenotype prior to the onset of rheumatoid arthritis. Ann Rheum Dis. 2015.
Priscilla Kerkman: Identification and characterisation of ACPA-producing B cells in RA. Awarded: 2017
Current PhD projects
Ayla Kempers: The Anti-Citrullinated Protein Antibody immune response and its effector functions in Rheumatoid Arthritis
Hendy Kristyanto: Functional characterization of citrullinated-antigen-specific (memory) B cells and the development of strategies for antigen-specific depletion
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