Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis

Yuhsuke Ohmi, Wataru Ise, Akira Harazono, Daisuke Takakura, Hidehiro Fukuyama, Yoshihiro Baba, Masashi Narazaki, Hirofumi Shoda, Nobunori Takahashi, Yuki Ohkawa, Shuting Ji, Fumihiro Sugiyama, Keishi Fujio, Atsushi Kumanogoh, Kazuhiko Yamamoto, Nana Kawasaki, Tomohiro Kurosaki, Yoshimasa Takahashi, Koichi Furukawa

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

Abstract

Rheumatoid arthritis (RA)-associated IgG antibodies such as anti-citrullinated protein antibodies (ACPAs) have diverse glycosylation variants; however, key sugar chains modulating the arthritogenic activity of IgG remain to be clarified. Here, we show that reduced sialylation is a common feature of RA-associated IgG in humans and in mouse models of arthritis. Genetically blocking sialylation in activated B cells results in exacerbation of joint inflammation in a collagen-induced arthritis (CIA) model. On the other hand, artificial sialylation of anti-type II collagen antibodies, including ACPAs, not only attenuates arthritogenic activity, but also suppresses the development of CIA in the antibody-infused mice, whereas sialylation of other IgG does not prevent CIA. Thus, our data demonstrate that sialylation levels control the arthritogenicity of RA-associated IgG, presenting a potential target for antigen-specific immunotherapy.

Original languageEnglish
Article number11205
JournalNature communications
Volume7
DOIs
Publication statusPublished - Apr 5 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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