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Secretory form of rheumatoid arthritis–associated autoantibodies in serum are mainly of the IgM isotype, suggesting a continuous reactivation of autoantibody responses at mucosal surfaces
  1. Myrthe A M van Delft1,
  2. Diane van der Woude1,
  3. René E M Toes1,
  4. Leendert A Trouw2
  1. 1 Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Dr Leendert A Trouw, Department of Immunohematology and Blood transfusion, Leiden University Medical Center, Leiden 2300 RC, The Netherlands; l.a.trouw{at}

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Several lines of evidence obtained in recent years indicate a role of mucosal surfaces in the development of autoimmune responses associated with rheumatoid arthritis (RA). Therefore, more attention is going to the influence of the microbiome in RA development. Secretory antibodies are typically produced at mucosal surfaces and transported through epithelial cells for secretion at the luminal site. Importantly, secretory antibodies comprise both IgM and IgA, and both isotypes can harbour a J-chain that binds to the polymeric Ig receptor (pIgR).1 Following transport through epithelial cells, the antibodies are enzymatically released at the luminal site by cleavage of the pIgR leaving a fragment of the receptor, the secretory component (SC) bound to the immunoglobulin. SC-containing antibodies can however also be detected systemically in the circulation, although the mechanism by which these SC-containing antibodies arise in serum is still unclear.2 Interestingly, antigen-specific secretory antibodies are present in serum after mucosal immunisation,3 indicating that the presence of secretory antibodies may provide information about their origin: the mucosa. Well-known autoantibodies in RA are rheumatoid factor (RF), ACPA (against citrullinated proteins) and anti-CarP (against carbamylated proteins).4 Secretory RF (SC-RF) and secretory ACPA (SC-ACPA) have been detected in RA sera,5 6 indicating a mucosal origin. Although it is often postulated that SC-containing autoantibodies are of the IgA isotype, this is unknown as both IgM and IgA can harbour SC. Nonetheless, it is important to define the isotype of SC-containing autoantibodies as this provides relevant information on the type of B cell (re)activated at …

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  • Handling editor Josef S Smolen

  • Contributors MAMvD set up the study design and performed the experiments, as well as the analysis, interpretation of the data, drafting the article and approval of the final manuscript. DvdW and REMT contributed to the interpretation of the data, revising the manuscript and approval of the final manuscript. LAT contributed to study design, interpretation of the data, revising the manuscript and approval of the final manuscript.

  • Funding This work was supported by the Dutch Arthritis Foundation (14-2-402) and the IMI JU–funded project BeTheCure (115142-2). DvdW is supported by a ZON-MW Veni grant, REMT by a ZON-MW Vici grant and LAT is supported by a ZON-MW Vidi grant (91712334).

  • Competing interests REMT and LAT are listed as inventors in a patent application regarding the detection of anti-CarP antibodies for RA.

  • Patient consent Not required.

  • Ethics approval Ethical committee of the LUMC.

  • Provenance and peer review Not commissioned; externally peer reviewed.