| First Author | Pagan JD | Year | 2018 |
| Journal | Cell | Volume | 172 |
| Issue | 3 | Pages | 564-577.e13 |
| PubMed ID | 29275858 | Mgi Jnum | J:259181 |
| Mgi Id | MGI:6120242 | Doi | 10.1016/j.cell.2017.11.041 |
| Citation | Pagan JD, et al. (2018) Engineered Sialylation of Pathogenic Antibodies In Vivo Attenuates Autoimmune Disease. Cell 172(3):564-577.e13 |
| abstractText | Self-reactive IgGs contribute to the pathology of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Paradoxically, IgGs are used to treat inflammatory diseases in the form of high-dose intravenous immunoglobulin (IVIG). Distinct glycoforms on the IgG crystallizable fragment (Fc) dictate these divergent functions. IgG anti-inflammatory activity is attributed to sialylation of the Fc glycan. We therefore sought to convert endogenous IgG to anti-inflammatory mediators in vivo by engineering solubilized glycosyltransferases that attach galactose or sialic acid. When both enzymes were administered in a prophylactic or therapeutic fashion, autoimmune inflammation was markedly attenuated in vivo. The enzymes worked through a similar pathway to IVIG, requiring DC-SIGN, STAT6 signaling, and FcgammaRIIB. Importantly, sialylation was highly specific to pathogenic IgG at the site of inflammation, driven by local platelet release of nucleotide-sugar donors. These results underscore the therapeutic potential of glycoengineering in vivo. |
