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.
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.|Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Yuhsuke
authors.initials: Y
authors.lastname: Ohmi
authors.affiliation: Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center and Graduate School of Frontier Biosciences, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ise
authors.affiliation: Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Harazono
authors.affiliation: Laboratory of Proteome Science, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takakura
authors.affiliation: Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, 1-7-22, Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Fukuyama
authors.affiliation: Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center and Graduate School of Frontier Biosciences, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Baba
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Narazaki
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Shoda
authors.affiliation: Department of Orthopedics, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
authors.forename: Nobunori
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.|Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto, Kasugai 487-8501, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohkawa
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
authors.forename: Shuting
authors.initials: S
authors.lastname: Ji
authors.affiliation: Laboratory Animal Resource Center, University of Tsukuba, 1-1-1 Ten-no-dai, Tsukuba 305-8575, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Sugiyama
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Fujio
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.|Laboratory of Proteome Science, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Kawasaki
authors.affiliation: Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center and Graduate School of Frontier Biosciences, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.|Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, 1-7-22, Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.|Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto, Kasugai 487-8501, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001323:Autoantibodies / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D002240:Carbohydrate Sequence; D024043:Collagen Type II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D012794:Sialic Acids / Q000276:immunology / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D024043:Collagen Type II; D007074:Immunoglobulin G; D012794:Sialic Acids