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The extensive glycosylation of the ACPA variable domain observed for ACPA-IgG is absent from ACPA-IgM
  1. Ayla C Kempers1,
  2. Lise Hafkenscheid1,
  3. Annemarie L Dorjée1,
  4. Eleni Moutousidou1,
  5. Fleur S van de Bovenkamp2,
  6. Theo Rispens2,
  7. Leendert A Trouw1,
  8. Maikel van Oosterhout3,
  9. Tom WJ Huizinga1,
  10. René Toes1,
  11. Hans Ulrich Scherer1
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Amsterdam, The Netherlands
  3. 3Department of Rheumatology, Groene Hart Ziekenhuis, Gouda, The Netherlands
  1. Correspondence to Dr Hans Ulrich Scherer, Department of Rheumatology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands; H.U.Scherer{at}lumc.nl

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Recently, we described the presence of highly sialylated N-linked glycans in the antigen-binding fragment (Fab) of almost all anti-citrullinated protein antibody (ACPA) IgG molecules.1 2 These glycans could not be found on several other autoantibody systems analysed. Given the low affinity of ACPA,3 this observation raises the intriguing possibility that citrullinated antigen-specific B cells could be selected based on the presence of glycans in the variable domain, rather than on affinity for their cognate antigen. N-glycosylation requires the presence of specific consensus sequences in the amino acid backbone of proteins.4 However, only few human germline Ig variable region genes encode for such sequences.5 So far, we could identify several N-glycosylation sites in ACPA-IgG Fab-domains using mass spectrometry, but none of these were encoded in the germline sequence.1 This suggests that the extensive presence of N-glycans in ACPA-IgG Fab-domains results from somatic mutations. Moreover, it indicates that the ACPA response matures under the influence of T-cell help, presumably in germinal centres, and makes it conceivable that the introduction of N-glycosylation sites …

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