Monoclonal antibody against citrullinated peptides obtained from rheumatoid arthritis patients reacts with numerous citrullinated microbial and food proteins

Reina Tsuda, Tatsuhiko Ozawa, Eiji Kobayashi, Hiroshi Hamana, Hirofumi Taki, Kazuyuki Tobe, Eiji Sugiyama, Masahiro Iwamoto, Johji Imura, Hiroyuki Kishi*, Atsushi Muraguchi

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

28 被引用数 (Scopus)

抄録

Objective To investigate the reactivity of monoclonal anti-citrullinated protein antibody (ACPA) obtained from peripheral blood B cells of rheumatoid arthritis (RA) patients with human autoantigens as well as environmental proteins by determining the essential epitope for the ACPA. Methods A human monoclonal ACPA (cyclic citrullinated peptide antibody 1 [CCP-Ab1]) was obtained by screening peripheral blood lymphocytes from 31 patients with RA using a novel monoclonal antibody-secreting cell (ASC) screening system, the immunospot-array assay on a chip. The essential epitope for CCP-Ab1 was determined using epitope mapping. Then, human, microbial, and plant proteins that share the essential epitope identified were searched using BLAST. Finally, representative proteins identified by the search were produced in vitro, and their reactivity with CCP-Ab1 was examined. Results CCP-Ab1 bound CCP in a citrulline-indispensable manner. In CCP, the 6 amino acid residues required for CCP-Ab1 binding were identified. In the BLAST search, 38 human, 56 viral, 1,383 fungal, 547 bacterial, and 1,072 plant proteins were found to share the essential epitope, and CCP-Ab1 reacted with all of the recombinant citrullinated proteins tested, which included the various environmental factors, such as various plant proteins that are part of the daily diet. Conclusion Our findings demonstrate, for the first time, that a monoclonal ACPA (CCP-Ab1) derived from RA patients cross-reacts not only with various autoantigens but also with numerous plant and microbial proteins. We propose that countless environmental factors, including microbes and diet, may trigger the generation of ACPAs that then cross-react with various citrullinated human autoantigens through molecular mimicry to induce RA.

本文言語英語
ページ(範囲)2020-2031
ページ数12
ジャーナルArthritis and Rheumatology
67
8
DOI
出版ステータス出版済み - 2015/08/01

ASJC Scopus 主題領域

  • 免疫アレルギー学
  • リウマチ学
  • 免疫学

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