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

doi:10.1038/ncomms11205

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

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118 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 language	English
Article number	11205
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11205
Publication status	Published - Apr 5 2016
Externally published	Yes

All Science Journal Classification (ASJC) codes

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

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Ohmi, Y., Ise, W., Harazono, A., Takakura, D., Fukuyama, H., Baba, Y., Narazaki, M., Shoda, H., Takahashi, N., Ohkawa, Y., Ji, S., Sugiyama, F., Fujio, K., Kumanogoh, A., Yamamoto, K., Kawasaki, N., Kurosaki, T., Takahashi, Y., & Furukawa, K. (2016). Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis. Nature communications, 7, [11205]. https://doi.org/10.1038/ncomms11205

Ohmi, Y, Ise, W, Harazono, A, Takakura, D, Fukuyama, H, Baba, Y, Narazaki, M, Shoda, H, Takahashi, N, Ohkawa, Y, Ji, S, Sugiyama, F, Fujio, K, Kumanogoh, A, Yamamoto, K, Kawasaki, N, Kurosaki, T, Takahashi, Y & Furukawa, K 2016, 'Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis', Nature communications, vol. 7, 11205. https://doi.org/10.1038/ncomms11205

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title = "Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis",

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.",

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

note = "Funding Information: Acknowledgements We thank R. Casellas (National Institute of Arthritis and Musculoskeletal and Skin Diseases) for AID-Cre mice, T. Takahashi (Tsukuba University) for Flp mice, T. Kitamura (University of Tokyo) for vectors and R. Holmdahl (Lund University) for ACC4/M2139 mAbs. We also thank Ms. E. Izumiyama, T. Mizuno, Y. Nakayasu, E. Kobayashi and Mr. H. Takei for technical assistance. This research was supported by the grants received by T.K., Y.T. and K.F. from the Japan Science and Technology Agency, Core Research of Evolutional Science and Technology, and by Y.O. from JSPS KAKENHI Grant Number 26860321, Nagoya University Hospital Funding for Clinical Research, Yokoyama-Rinsyo foundation and Takeda Science Foundation.",

year = "2016",

month = apr,

day = "5",

doi = "10.1038/ncomms11205",

language = "English",

volume = "7",

journal = "Nature Communications",

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T1 - Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis

AU - Ohmi, Yuhsuke

AU - Ise, Wataru

AU - Harazono, Akira

AU - Takakura, Daisuke

AU - Fukuyama, Hidehiro

AU - Baba, Yoshihiro

AU - Narazaki, Masashi

AU - Shoda, Hirofumi

AU - Takahashi, Nobunori

AU - Ohkawa, Yuki

AU - Ji, Shuting

AU - Sugiyama, Fumihiro

AU - Fujio, Keishi

AU - Kumanogoh, Atsushi

AU - Yamamoto, Kazuhiko

AU - Kawasaki, Nana

AU - Kurosaki, Tomohiro

AU - Takahashi, Yoshimasa

AU - Furukawa, Koichi

N1 - Funding Information: Acknowledgements We thank R. Casellas (National Institute of Arthritis and Musculoskeletal and Skin Diseases) for AID-Cre mice, T. Takahashi (Tsukuba University) for Flp mice, T. Kitamura (University of Tokyo) for vectors and R. Holmdahl (Lund University) for ACC4/M2139 mAbs. We also thank Ms. E. Izumiyama, T. Mizuno, Y. Nakayasu, E. Kobayashi and Mr. H. Takei for technical assistance. This research was supported by the grants received by T.K., Y.T. and K.F. from the Japan Science and Technology Agency, Core Research of Evolutional Science and Technology, and by Y.O. from JSPS KAKENHI Grant Number 26860321, Nagoya University Hospital Funding for Clinical Research, Yokoyama-Rinsyo foundation and Takeda Science Foundation.

PY - 2016/4/5

Y1 - 2016/4/5

N2 - 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.

AB - 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.

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VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 11205

ER -

Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis

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