Crosstalk between B cells and neutrophils in rheumatoid arthritis

Utsa Karmakar, Sonja Vermeren*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

AbstractRheumatoid arthritis (RA) is a chronic, systemic autoimmune disease without known cure that primarily affects synovial joints. RA has a prevalence of approxi-mately 1% of the population worldwide. A vicious circle between two critical im-mune cell types, B cells and neutrophils, develops and promotes disease. Pathogenic anti- citrullinated protein antibodies (ACPA) directed against a range of citrullinated epitopes are abundant in both plasma and synovial fluid of RA patients. In addi-tion to stimulating numerous cell types, ACPA and other autoantibodies, notably rheumatoid factor, form immune complexes (ICs) that potently activate neutrophils. Attracted to the synovium by abundant chemokines, neutrophils are locally stimu-lated by ICs. They generate cytokines and release cytotoxic compounds including neutrophil extracellular traps (NETs), strands of decondensed chromatin decorated with citrullinated histones and granule- derived neutrophil proteins, which are par-ticularly abundant in the synovial fluid. In this way, neutrophils generate citrulli-nated epitopes and release peptidylarginine deiminase (PAD) enzymes capable of citrullinating extracellular proteins in the rheumatic joint, contributing to renewed ACPA generation. This review article focusses on the central function of citrullina-tion, a post- translational modification of arginine residues in RA. The discussion includes ACPA and related autoantibodies, somatic hypermutation- mediated es-cape from negative selection by autoreactive B cells, promotion of the dominance of citrullinated antigens by genetic and lifestyle susceptibility factors and the vicious circle between ACPA- producing pathogenic B cells and NET- producing neutrophils in RA.
Original languageEnglish
Pages (from-to)689-700
Number of pages12
JournalImmunology
Volume164
Issue number4
DOIs
Publication statusPublished - 3 Sept 2021

Keywords / Materials (for Non-textual outputs)

  • anti-citrullinated protein antibodies
  • B cells
  • citrullination
  • dysbiosis
  • immune complexes
  • neutrophil extracellular traps
  • neutrophils
  • peptidylarginine deiminase
  • rheumatoid arthritis

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