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Take the bitter with the sweet; Targeting hyperglycosylation of the auto-antibodies specific for rheumatoid arthritis.

Ons afweersysteem zorgt ervoor dat ziekteverwekkers zoals virussen, bacteriën en schimmels worden opgespoord en vernietigd. Hierdoor blijven wij gezond. Bij sommige mensen keert het afweersysteem zich tegen het eigen lichaam. Het herkent de eigen lichaamsweefsels en komt in actie om de zogenaamde ‘indringers’ te vernietigen. Zo ontstaat een chronische ontsteking. Bij reumapatiënten gaat er iets mis in de communicatie tussen de afweercellen, waardoor er antistoffen worden gevormd die zich tegen lichaamseigen eiwitten richten. Kort geleden hebben we ontdekt dat deze auto-antistoffen over een unieke eigenschap beschikken omdat ze groter zijn dan andere antistoffen. Dit wordt veroorzaakt door een extra suikermolecuul dat door de afweercellen aan het antistof wordt gezet. Het is onbekend waarom dit gebeurt en of dit bijdraagt aan het ontstaan van reuma. Dit project heeft tot doel de betekenis en gevolgen van deze extra suikerstaart aan de reuma-specifieke auto-antistoffen op te helderen.

Producten

Titel: 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.
Auteur: Vergroesen RD, Slot LM, Hafkenscheid L, Koning MT, van der Voort EIH, Grooff CA, Zervakis G, Veelken H, Huizinga TWJ, Rispens T, Scherer HU, Toes REM.
Magazine: Annals of the Rheumatic Diseases
Link: http://ard.bmj.com/content/early/2017/08/22/annrheumdis-2017-212052.long
Titel: Structural Analysis of Variable Domain Glycosylation of Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis Reveals the Presence of Highly Sialylated Glycans
Auteur: Hafkenscheid L, Bondt A, Scherer HU, Huizinga TW, Wuhrer M, Toes RE, Rombouts Y
Magazine: Molecular and Cellular Proteomics
Link: http://www.mcponline.org/content/16/2/278.long
Titel: Antibodies and B cells recognising citrullinated proteins display a broad cross-reactivity towards other post-translational modifications
Auteur: T Kissel, S Reijm, LM Slot, M Cavallari, CM Wortel, RD Vergroesen, G Stoeken-Rijsbergen, JC Kwekkeboom, Kampstra, EWN Levarht, JW Drijfhout, H Bang, KM Bonger, GMC Janssen, PA van Veelen, TWJ Huizinga, HU Scherer, M Reth, REM Toes
Magazine: Annals of the Rheumatic Diseases
Link: https://ard.bmj.com/content/79/4/472
Titel: 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
Auteur: Kerkman PF, Kempers AC, van der Voort EI, van Oosterhout M, Huizinga TW, Toes RE, Scherer HU.
Magazine: Annals of Rheumatic Diseases
Link: http://ard.bmj.com/content/75/12/2201.long
Titel: N-Linked Glycans in the Variable Domain of IgG Anti–Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis
Auteur: Lise Hafkenscheid MSc Emma de Moel MD Irene Smolik PhD Stacey Tanner MD Xiaobo Meng PhD Bas C. Jansen PhD Albert Bondt PhD Manfred Wuhrer PhD Tom W. J. Huizinga MD, PhD Rene E. M. Toes PhD Hani El-Gabalawy MD Hans U. Scherer MD, PhD
Magazine: Arthritis and Rheumatology
Link: https://onlinelibrary.wiley.com/doi/full/10.1002/art.40920
Titel: The B cell response to citrullinated antigens in the development of rheumatoid arthritis
Auteur: Scherer, Hans Ulrich, Huizinga, Tom W. J., Krönke, Gerhard, Schett, Georg, Toes, Rene E. M.
Magazine: Nature Reviews Rheumatology
Link: https://www.ncbi.nlm.nih.gov/pubmed/29416134
Titel: N-Glycosylation Site Analysis of Citrullinated Antigen-Specific B-Cell Receptors Indicates Alternative Selection Pathways During Autoreactive B-Cell Development
Auteur: Rochelle D Vergroesen 1 , Linda M Slot 1 , Barbera D C van Schaik 2 , Marvyn T Koning 3 , Theo Rispens 4 , Antoine H C van Kampen 2 5 , René E M Toes 1 , Hans U Scherer 1
Magazine: Frontiers in Immunology
Link: https://pubmed.ncbi.nlm.nih.gov/31572358/
Titel: Identification and characterisation of citrullinated antigen-specific B cells in peripheral blood of patients with rheumatoid arthritis
Auteur: Kerkman PF, Fabre E, van der Voort EI, Zaldumbide A, Rombouts Y, Rispens T, Wolbink G, Hoeben RC, Spits H, Baeten DL, Huizinga TW, Toes RE, Scherer HU
Magazine: Annals of the Rheumatic Diseases
Link: http://ard.bmj.com/content/75/6/1170
Titel: Generation and Characterization of Anti–Citrullinated Protein Antibody–Producing B Cell Clones From Rheumatoid Arthritis Patients
Auteur: Kristine Germar PhD Cynthia M. Fehres PhD Hans U. Scherer MD, PhD Nathalie van Uden Sabrina Pollastro PhD Nataliya Yeremenko PhD Monika Hansson Priscilla F. Kerkman PhD Ellen I. H. van der Voort Evan Reed PhD Hanna Maassen Mark J. Kwakkenbos PhD Arjen Q. Bakker Lars Klareskog PhD Vivianne Malmström PhD Niek de Vries MD, PhD René E. M. Toes PhD Karin Lundberg PhD Hergen Spits PhD Dominique L. Baeten MD, PhD
Magazine: Arthritis and Rheumatology
Link: https://onlinelibrary.wiley.com/doi/full/10.1002/art.40739
Titel: Adaptive antibody diversification throughN-linked glycosylation of the immunoglobulin variable region
Auteur: van de Bovenkamp, Fleur S., Derksen, Ninotska I. L., Ooijevaar-de Heer, Pleuni, van Schie, Karin A., Kruithof, Simone, Berkowska, Magdalena A., van der Schoot, C. Ellen, IJspeert, Hanna, van der Burg, Mirjam, Gils, Ann, Hafkenscheid, Lise, Toes, René E. M., Rombouts, Yoann, Plomp, Rosina, Wuhrer, Manfred, van Ham, S. Marieke, Vidarsson, Gestur, Rispens, Theo
Magazine: Proceedings of the National Academy of Sciences
Link: https://www.ncbi.nlm.nih.gov/pubmed/29432186
Titel: Variable domain glycosylation of ACPA-IgG: A missing link in the maturation of the ACPA response?
Auteur: Kempers, Ayla C., Hafkenscheid, Lise, Scherer, Hans Ulrich, Toes, René E.M.
Magazine: Clinical Immunology
Link: https://www.sciencedirect.com/science/article/pii/S1521661617305971?via%3Dihub
Titel: On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis
Auteur: Theresa Kissel, Karin Anna van Schie, Lise Hafkenscheid, Anders Lundquist, Heidi Kokkonen, Manfred Wuhrer, Tom WJ Huizinga, Hans Ulrich Scherer, René Toes, Solbritt Rantapää-Dahlqvist
Magazine: Annals of the Rheumatic Diseases
Link: https://ard.bmj.com/content/78/12/1616
Titel: Extensive glycosylation of ACPA-IgG variable domains in rheumatoid arthritis
Auteur: Lise Hafkenscheid
Titel: Cross reactivity as an inducer of autoimmunity
Auteur: Scientific presentation by Prof Toes
Link: https://www.eular.org/congress.cfm
Titel: Take the bitter with the sweet; on the role of variable domain glycans and the breach of tolerance of auto-reactive B-cells in Rheumatoid Arthritis
Auteur: Scientific presentation by Prof Toes
Titel: Zooming in on autoreactive B cell responses in RA
Auteur: Rene Toes
Titel: Tertiary lymphoid structures and B cells in inflammation and cancer
Auteur: Scientific presentation by Prof Toes
Link: https://www.lumc.nl/over-het-lumc/nieuws/2020/Maart
Titel: The introduction of N-linked glycans in the variable domain of Anti-NVVI 2017: Citrullinated Protein Antibodies marks the development of Rheumatoid Arthritis
Auteur: Lise Hafkenscheid
Link: https://www.dutchsocietyimmunology.nl/
Titel: Anti-Modified Protein Antibodies in (pre-)RA; on antigen-reactivity and glycosylation
Auteur: Scientific presentation by Prof Toes
Link: https://acrabstracts.org/
Titel: Glycosylation of antibodies in autoimmune diseases
Auteur: Scientific presentation by Prof Toes
Link: https://www.gfid-ev.de/dsa.htm
Titel: Alterations in the antibody repertoire and sugar modulation as cause for autoimmunity
Auteur: H.U. Scherer
Titel: Auto-antibody modification – Turning up the heat
Auteur: Scientific presentation by Prof Toes
Link: https://kuleuvencongres.be/ewrr2020/home
Titel: B Cell Receptor Sequencing of Anti-Citrullinated Protein Antibody (ACPA-)expressing B Cells Indicates a Selective Advantage For The Introduction of N-Glycosylation Sites During Somatic Hypermutation
Auteur: H.U. Scherer
Titel: Post-translational modified protein antibodies in RA: searching for the eye of the storm
Auteur: Rene Toes
Titel: Extensive glycosylation of ACPA-IgG variable domains in rheumatoid arthritis
Auteur: Lise Hafkenscheid
Titel: Introduction of N-glycosylation sites in ACPA-IgG B cells
Auteur: Rochelle Vergroesen
Titel: Post-translational modifications of antibodies: Where there is smoke, there is fire
Auteur: Scientific presentation by Prof Toes
Link: https://www.eular.org/
Titel: N-glycosylation sites in anti-citrullinated protein antibody (ACPA-) expressing B-cell receptors are selectively introduced at high frequency during somatic hypermutation
Auteur: Rochelle Vergroesen
Titel: Extensive glycosylation of ACPA-IgG variable domains in rheumatoid arthritis
Auteur: Lise Hafkenscheid
Titel: Autoantibodies and their glycosylation during emergence of RA
Auteur: H.U. Scherer
Titel: N-glycosylation sites in the variable domain of B cell receptors specific for citrullinated antigens
Auteur: H.U. Scherer
Titel: Autoreactive B cells and antibodies in the pre-RA phase of disease; on glycosylation and antigen-reactivity
Auteur: Scientific presentation by Prof Toes
Link: https://fnih.org/what-we-do/programs/ifra2019
Titel: B cells in Rheumatoid Arthritis
Auteur: Rene Toes
Link: https://bcellnetwork.nl/2018/
Titel: Take the bitter with the sweet; on the role of variable domain glycans and the breach of tolerance of auto-reactive B-cells in Rheumatoid Arthritis
Auteur: Scientific presentation by Prof Toes
Link: https://www.humanimmunology.org/about/
Titel: Extensive glycosylation of ACPA-IgG variable domains in rheumatoid arthritis
Auteur: Lise Hafkenscheid
Titel: Emerging biomarkers in Rheumatoid Arthritis
Auteur: Rene Toes
Link: http://www.precisionmedicineautoimmunity.org/
Titel: Identification and characterization of anti-citrullinated protein antibody-producing B clls en patients with Rheumatoid Arthritis
Auteur: Priscilla F. Kerkman
Titel: Carol Nachman Prize 2018
Link: https://www.wiesbadener-kurier.de/lokales/wiesbaden/

Onderwerpen

Kenmerken

Projectnummer:
91214031
Looptijd: 100%
Looptijd: 100 %
2015
2021
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
Prof. dr. R.E.M. Toes
Verantwoordelijke organisatie:
Leiden University Medical Center