Publications by authors named "R D Vergroesen"

The hallmark autoantibodies in rheumatoid arthritis are characterized by variable domain glycans (VDGs). Their abundant occurrence results from the selective introduction of N-linked glycosylation sites during somatic hypermutation, and their presence is predictive for disease development. However, the functional consequences of VDGs on autoreactive B cells remain elusive.

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Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting 1% of the world population. RA is associated with the presence of autoantibodies, of which anti-citrullinated protein antibodies (ACPA) are most prominent. ACPA are produced by citrullinated antigen-binding B cells that have presumably survived tolerance checkpoints.

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RAG complexes recognise (cryptic) RSS sites both in and outside immunoglobulin sites. Excision circles may be reinserted into V(D)J rearrangements as long templated insertions to diversify the adaptive immune repertoire. We show that such VDJ with templated insertions are incidentally found in the repertoire of healthy donors.

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Article Synopsis
  • Autoantibodies against specific post-translational modifications (PTMs) like citrulline and acetyllysine are important in understanding rheumatoid arthritis (RA) and how they activate B-cell receptors (BCRs).
  • The study produced monoclonal antibodies from B cells stimulated by citrullinated or acetylated antigens to analyze their cross-reactivity with different PTMs.
  • Findings revealed that most monoclonal antibodies were highly cross-reactive to multiple PTMs and that B cells with CP-reactive BCRs can be activated by various PTM-antigens, which is crucial for understanding their role in RA development.
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Many autoimmune diseases are hallmarked by autoreactive B and plasma cell responses that are directly or indirectly involved in disease pathogenesis. These B-cell responses show large variability between diseases, both in terms of the secreted autoantibody repertoire and the dynamics and characteristics of the underlying B-cell responses. Hence, different mechanisms have been proposed to explain the emergence of autoreactive B cells in an otherwise self-tolerant immune system.

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