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Low avidity observed for anti-citrullinated peptide antibody is not a general phenomenon for autoantibodies
  1. Hisakata Yamada1,2,3,
  2. Akihisa Haraguchi2,
  3. Tomomi Tsuru4,
  4. Masakazu Kondo3,
  5. Fumiaki Sagawa4,
  6. Hiroaki Niiro5,
  7. Yasuharu Nakashima2
  1. 1 Department of Clinical Immunology, Kyushu University Faculty of Medicine Graduate School of Medical Science, Fukuoka, Japan
  2. 2 Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  3. 3 Kondo Clinic for Rheumatology and Orthopaedics, Fukuoka, Japan
  4. 4 PS Clinic, Fukuoka, Japan
  5. 5 Department of Medical Education, Kyushu University, Fukuoka, Japan
  1. Correspondence to Dr Hisakata Yamada, Depaetment of Clinical Immunology, Kyushu University Faculty of Medicine Graduate School of Medical Science, Fukuoka 812-8582, Japan; hisakata{at}

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Anti-citrullinated protein antibody (ACPA) is specifically detected in patients with rheumatoid arthritis (RA) preceding disease onset. Hence, understanding the mechanism of ACPA production is important for elucidating the aetiology of RA. The avidity of serum antibody to an antigen increases with time, affinity maturation, in which B cells bearing high-affinity receptor generated via somatic hyper mutation (SHM) are selected in the germinal centre. However, it has been reported that the avidity of ACPA is lower than antibodies against recall antigens,1 although the underlying mechanism remains unclear. One possibility is that self-tolerance to citrullinated antigens, as demonstrated in mice,2 prevents the production of high-avidity ACPAs. Therefore, we investigated in this study whether low-avidity binding is unique to ACPA or common to autoantibodies.

Sera from RA patients positive for CCP2 by clinical laboratory tests (n=180) were screened for the presence of IgG against cyclic-citrullinated filaggrin (cfc1), citrullinated fibrinogen (cFib), α-enorase (cEno) and vimentin (cVim) peptides, and samples showing citrulline-specific binding compared with non-citrullinated peptides were selected (n=80) (online supplemental figure 1). The sera were also used for measuring avidity of IgG against diphtheria toxin (DT) and measles if seropositive. Sera from patients with RA with Sjogren syndrome (n=15) and …

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  • Handling editor Josef S Smolen

  • Contributors HY and AH equally contributed to this study by designing the concept, acquisition and analysis of the data, and drafting the manuscript. TT, MK and FS contributed to acquisition of data. HN and YN contributed to the interpretation of data and critically reviewed the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.