Prof. dr. Rene Toes

Department of Rheumatology, LUMC Leiden, The Netherlands

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 in rheumatic disease 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 cure of B cell mediated auto-immune diseases.

Recent publications

Full publication list: : https://pubmed.ncbi.nlm.nih.gov/?term=toes%2C+r&sort=date

  1. Antibodies and B Cells Recognising Citrullinated Proteins Display a Broad Cross-Reactivity Towards Other Post-Translational Modifications.  T Kissel, S Reijm, L M Slot, M Cavallari, C M Wortel, R D Vergroesen, G Stoeken-Rijsbergen, J C Kwekkeboom, A Kampstra, E Levarht, J W Drijfhout, H Bang, K M Bonger, G Janssen, P A van Veelen, T Huizinga, H U Scherer, M Reth, R Toes. Ann Rheum Dis. 79: 472-480, 2020.
  2. Pathogenic effector function of ACPA: Where do we stand? R. Toes and D. Pisetsky. Rheum. Dis. 78: 716-721; 2019
  3. The B cell response to citrullinated antigens in the development of rheumatoid arthritis. Scherer, H.U., Huizinga, T.W.J., Kronke, G., Schett, G. and R. E. M. Toes. Nature Reviews Rheumatology 14: 157-169; 2018
  4. 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. Vergroesen RD, Slot LM, Hafkenscheid L, Koning MT, van der Voort EIH, Grooff CA, Zervakis G, Veelken H, Huizinga TWJ, Rispens T, Scherer HU, REM Toes. Ann Rheum Dis 77; 956-958; 2018.
  5. Breach of autoreactive B cell tolerance by post-translationally modified proteins. Dekkers JS, Verheul MK, Stoop JN, Liu B, Ioan-Facsinay A, van Veelen PA, de Ru AH, Janssen GMC, Hegen M, Rapecki S, Huizinga TWJ, Trouw LA, REM Toes. Ann Rheum Dis. 76:1449-1457: 2017.
  6. Extensive glycosylation of ACPA-IgG variable domains modulates binding to citrullinated antigens in rheumatoid arthritis. Rombouts Y, Willemze A, van Beers JJ, Shi J, Kerkman PF, van Toorn L, Janssen GM, Zaldumbide A, Hoeben RC, Pruijn GJ, Deelder AM, Wolbink G, Rispens T, van Veelen PA, Huizinga TW, Wuhrer M, Trouw LA, Scherer HU, REM Toes. Ann Rheum Dis.75:578-85; 2016.
  7. Crossreactivity to vinculin and microbes provides a molecular basis for HLA-based protection against rheumatoid arthritis. van Heemst J, Jansen DT, Polydorides S, Moustakas AK, Bax M, Feitsma AL, Bontrop-Elferink DG, Baarse M, van der Woude D, Wolbink GJ, Rispens T, Koning F, de Vries RR, Papadopoulos GK, Archontis G, Huizinga TW, REM Toes RE. Nat Commun. 5;6:6681.2015.