[HTML][HTML] Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis

Y Ohmi, W Ise, A Harazono, D Takakura… - Nature …, 2016 - nature.com
Y Ohmi, W Ise, A Harazono, D Takakura, H Fukuyama, Y Baba, M Narazaki, H Shoda…
Nature communications, 2016nature.com
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 …
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.
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