Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis

• Published in: Nature Communications Vol. 7; no. 7; p. 11205
• Main Authors: 杉山 文博, Ohmi Yuhsuke, Ise Wataru, Harazono Akira, Takakura Daisuke, Fukuyama Hidehiro, Baba Yoshihiro, Narazaki Masashi, Shoda Hirofumi, Takahashi Nobunori, Ohkawa Yuki, Ji Shuting, Sugiyama Fumihiro, Fujio Keishi, Kumanogoh Atsushi, Yamamoto Kazuhiko, Kawasaki Nana, Kurosaki Tomohiro, Takahashi Yoshimasa, Furukawa Koichi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 05.04.2016; Nature Publishing Group UK; Nature Portfolio
• Subjects: 631/250/249/1313/498; 631/250/251; 64; 64/110; 64/60; 692/308; 692/420/2780; 82; 82/1; 82/51; 82/58; 82/83; Amino Acid Sequence; Animals; Arthritis, Experimental - immunology; Arthritis, Experimental - metabolism; Arthritis, Experimental - pathology; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Autoantibodies - chemistry; Autoantibodies - immunology; Autoantibodies - metabolism; Carbohydrate Sequence; Collagen Type II - immunology; Collagen Type II - metabolism; Humanities and Social Sciences; Humans; Immunoglobulin G - chemistry; Immunoglobulin G - immunology; Immunoglobulin G - metabolism; Immunotherapy; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Transgenic; Molecular Sequence Data; multidisciplinary; Protein Processing, Post-Translational; Rheumatoid arthritis; Science; Science (multidisciplinary); Sialic Acids - immunology; Sialic Acids - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11205

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.